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De Martino S, Capasso B, Cis L, D'Orsi L, Canali G, Capasso P, De Gaetano A, Mercantini P, Mascagni D, Gaetano C, Farsetti A, Lo Presti E. Role of innate immunity in tumor microenvironment of HPV-associated anal cancer: The hypothetical beneficial role of γδ T cells. Crit Rev Oncol Hematol 2025; 212:104771. [PMID: 40412574 DOI: 10.1016/j.critrevonc.2025.104771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2025] [Revised: 05/13/2025] [Accepted: 05/19/2025] [Indexed: 05/27/2025] Open
Abstract
HPV infection plays a crucial role in the formation of the tumor microenvironment, especially in tumors associated with the genital tract, anus, and oropharyngeal region. In this manuscript, we will discuss the main genetic characteristics of HPV and its transmission mechanisms, with a specific focus on the expression of the oncogenes E6 and E7. We will also address the major tumors HPV can generate and their associated epidemiology. In particular, persistent HPV infection induces the release of pro-inflammatory cytokines (such as IL-6 and IL-8), which promote angiogenesis and the recruitment of immunosuppressive immune cells. We will describe on the immune response to the infection, specifically in adaptive immunity, where the virus reduces the expression of MHC class I molecules on infected cells, preventing recognition by cytotoxic T cells. The innate immune response against HPV infection is often ineffective, allowing the virus to persist and contribute to tumor progression. The focus of this work will be on the innate response mediated by γδ T lymphocytes, a subset of CD3 + T cell. Indeed, they recognize HPV-infected cells without the need for antigen presentation by MHC molecules, secrete pro-inflammatory cytokines like IFN-γ and TNF-α, and directly kill HPV-infected cells through cytotoxic mechanisms. In summary, γδ T lymphocytes play an important role in the innate and adaptive immune response against HPV, but the effectiveness of their action can be reduced by the immune evasion mechanisms mediated by the virus. This may occur through the creation of an immunosuppressive environment with the release of immunosuppressive cytokines (such as IL-10 and TGF-β) that inhibit the function of these cells, allowing the virus to persist and contribute to tumor progression. This mechanism has not been well studied in the emerging anal cancer induced by HPV infection, so tracing the state of the art on these aspects could lead to an increase in research in this area and promote the creation of specific immunotherapies that enhance the role of these cells.
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Affiliation(s)
- Sara De Martino
- National Research Council of Italy, Institute for Systems Analysis and Computer Science "A. Ruberti, " BioMatLab (Biomathematics Laboratory), UCSC Largo A, Gemelli 8, Rome 00168, Italy
| | - Biagio Capasso
- Department of Surgical Sciences, La Sapienza University of Rome, Rome 00161, Italy
| | - Luca Cis
- National Research Council of Italy, Institute for Systems Analysis and Computer Science "A. Ruberti, " BioMatLab (Biomathematics Laboratory), UCSC Largo A, Gemelli 8, Rome 00168, Italy
| | - Laura D'Orsi
- National Research Council of Italy, Institute for Systems Analysis and Computer Science "A. Ruberti, " BioMatLab (Biomathematics Laboratory), UCSC Largo A, Gemelli 8, Rome 00168, Italy
| | - Giulia Canali
- Department of Medical Surgical sciences and translational medicines, Sapienza University of Rome, Rome 00185, Italy
| | - Pasquale Capasso
- Medical Polyspecialistic Department, Cardarelli Hospital, Via Antonio Cardarelli, 9, Naples 80131, Italy
| | - Andrea De Gaetano
- National Research Council of Italy, Institute for Systems Analysis and Computer Science "A. Ruberti, " BioMatLab (Biomathematics Laboratory), UCSC Largo A, Gemelli 8, Rome 00168, Italy; National Research Council of Italy (CNR), Institute for Biomedical Research and Innovation (IRIB), Palermo 90146, Italy; Department of Biomatics, Óbuda University, Bécsi Road 96/B, Budapest H-1034, Hungary
| | - Paolo Mercantini
- Department of Medical Surgical sciences and translational medicines, Sapienza University of Rome, Rome 00185, Italy
| | - Domenico Mascagni
- Department of Surgical Sciences, La Sapienza University of Rome, Rome 00161, Italy
| | - Carlo Gaetano
- Epigenetics Laboratory - Maugeri Scientific Clinical Institutes, Pavia 27100, Italy
| | - Antonella Farsetti
- National Research Council of Italy, Institute for Systems Analysis and Computer Science "A. Ruberti, " BioMatLab (Biomathematics Laboratory), UCSC Largo A, Gemelli 8, Rome 00168, Italy
| | - Elena Lo Presti
- National Research Council of Italy (CNR), Institute for Biomedical Research and Innovation (IRIB), Palermo 90146, Italy.
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Agarossi A, Savasi V, Frangipane C, Parisi F, Agarossi A, Dominoni M, Gardella B. High Risk of HPV-Related Preneoplastic and Neoplastic Vulvar Lesions in Women Living With HIV. J Low Genit Tract Dis 2025; 29:118-122. [PMID: 39652424 DOI: 10.1097/lgt.0000000000000864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Abstract
OBJECTIVE The authors aimed to investigate the epidemiology of human papilloma virus (HPV)-related preneoplastic and neoplastic vulvar lesions in a large cohort of women living with HIV (WLWH). MATERIALS AND METHODS The authors retrospectively selected 1,796 WLWH who had a gynecological examination, cervical cytology, high-risk (HR-) HPV test, vulvoscopy, and colposcopy with targeted biopsies when necessary between 1987 and 2020 at 2 Italian institutions. Univariable and multivariable regression analyses were carried out to test the association of the anamnestic and clinical data with the development of precancerous and cancerous lesions. RESULTS At baseline, 348 (19.4%) of 1,796 WLWH had genital warts, 30 (1.7%) had vulvar high-grade intraepithelial neoplasia (VHSIL), and 2 (0.1%) had squamous cell carcinoma of the vulva. Among 895 WLWH who had more than 1 year of follow-up, the authors found 40 (4.5%) new cases of VHSIL and 7 (0.8%) cases of vulvar cancer. The cumulative incidence of VHSIL and vulvar cancer was respectively 0.56 and 0.10 per 100 person-years. Risk factors independently associated with the development of vulvar HSIL and cancer included history of injection drug use ( p < .01), genital warts at baseline ( p < .001), HR-HPV test positivity at diagnosis ( p < .001), and severe immunodepression (CD4 cell count <200 cells/mL) at diagnosis ( p < .01). CONCLUSIONS WLWH are at high risk of vulvar high-grade intraepithelial neoplasia and cancer, especially those with severe immunodepression. A careful inspection of vulva, perineum and anus, possibly with the aid of colposcopy, should become part of the surveillance protocol of HIV-infected women.
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Affiliation(s)
- Alberto Agarossi
- Department of Obstetrics and Gynecology, L. Sacco Hospital, ASST Fatebenefratelli-Sacco, University of Milan, Milan, Italy
| | - Valeria Savasi
- Department of Biomedical and Clinical Sciences, V. Buzzi Children's Hospital, ASST Fatebenefratelli-Sacco, University of Milan, Milan, Italy
| | - Chiara Frangipane
- Department of Biomedical and Clinical Sciences, V. Buzzi Children's Hospital, ASST Fatebenefratelli-Sacco, University of Milan, Milan, Italy
| | - Francesca Parisi
- Department of Biomedical and Clinical Sciences, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Andrea Agarossi
- Neurosurgical Intensive Care Unit, Department of Neuroscience, San Carlo Borromeo Hospital, ASST Santi Paolo e Carlo, Milan, Italy
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Aizman L, Pakhchanian H, Barata Herrera D, Bibee K, Loss M. Top 50 Most Cited Articles in Transplant Dermatology: A Bibliometric Analysis. Dermatol Surg 2025; 51:365-369. [PMID: 39530507 DOI: 10.1097/dss.0000000000004486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
BACKGROUND Solid organ transplant recipients are at high risk for developing skin malignancies due to prolonged immunosuppression. The field of transplant dermatology (TD) has experienced a surge in research and clinical advancements, yet there is no quantitative evaluation estimating the impact of TD literature. OBJECTIVE Identify and characterize the most frequently cited TD articles. METHODS Institute For Scientific Information Web of Science was used to identify the 50 most cited research articles in TD. Results were reviewed by 3 independent authors. A network analysis was performed to assess collaboration patterns among coauthors. RESULTS Top articles held a combined total of 12,114 citations. The top-cited article was "Cancer incidence before and after kidney transplantation," by Vajdic and colleagues in the Journal of the American Medical Association (2006) with 872 citations. A total of 22 countries and 221 institutions were represented. CONCLUSION This bibliometric analysis offers a detailed overview of the most cited manuscripts in TD and illustrates the discoveries steering TD research and practice.
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Affiliation(s)
- Leora Aizman
- Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Haig Pakhchanian
- George Washington University School of Medicine and Health Sciences, Washington, District of Columbia
| | - Daniela Barata Herrera
- Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Kristin Bibee
- Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Manisha Loss
- Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Hanft W, Stankiewicz Karita H, Khorsandi N, Vohra P, Plotzker R. Sexually transmitted human papillomavirus and related sequelae. Clin Microbiol Rev 2025; 38:e0008523. [PMID: 39950806 PMCID: PMC11905373 DOI: 10.1128/cmr.00085-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/14/2025] Open
Abstract
SUMMARYMore than 40 types of sexually transmitted human papillomavirus (HPV) infect the oropharyngeal and anogenital mucosa-high-risk types are associated with precancerous and cancerous lesions of the cervix, vagina, vulva, penis, anus, and oropharynx, and low-risk types cause non-malignant disease, such as anogenital warts. Though most HPV infections resolve spontaneously, immunodeficiencies may result in persistent infection and increased risk of HPV-related sequelae. The mechanism by which HPV results in malignant transformation is multifaceted, involving interactions with numerous cellular pathways, the host immune system, and potentially the host microbiome. Vaccination against HPV is highly efficacious in the prevention of infection and related sequelae, and there now exist several approved formulations that protect against both high- and low-risk types. Despite the advent of vaccination, early detection and treatment of cervical and anal precancerous lesions continues to be integral to secondary prevention-molecular HPV testing, cytology, and tissue biopsy allow for triaging of patients, after which appropriate treatment with close follow-up can avert cancer development.
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Affiliation(s)
- Wyatt Hanft
- University of California, San Francisco, San Francisco, California, USA
| | | | - Nikka Khorsandi
- University of California, San Francisco, San Francisco, California, USA
| | - Poonam Vohra
- University of California, San Francisco, San Francisco, California, USA
| | - Rosalyn Plotzker
- University of California, San Francisco, San Francisco, California, USA
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Bertucci Zoccali M, Kimura CMS, Chapman BC, Cuming T, Fong CF, Jay N, Kaplan JA, Khan MJ, Messick CA, Simianu VV, Sugrue JJ, Barroso LF. Management of Anal Dysplasia: A Pragmatic Summary of the Current Evidence and Definition of Clinical Practices for Prevention, Diagnosis, and Treatment. Dis Colon Rectum 2025; 68:272-286. [PMID: 39641452 DOI: 10.1097/dcr.0000000000003444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2024]
Affiliation(s)
- Marco Bertucci Zoccali
- Columbia University Irving Medical Center/New York-Presbyterian Hospital, New York, New York
| | | | | | - Tamzin Cuming
- Homerton University Hospital NHS Trust, London, United Kingdom
| | - Carmen F Fong
- Icahn School of Medicine/Mount Sinai Beth Israel, New York, New York
- Wellstar Health Systems/ Hemorrhoid Centers of America, Atlanta, Georgia
| | - Naomi Jay
- University of California in San Francisco, Mount Zion Hospital, San Francisco, California
| | | | - Michelle J Khan
- Stanford University School of Medicine, Stanford, California
| | - Craig A Messick
- The University of Texas MD Anderson Cancer Center, Houston, Texas
| | | | | | - Luis F Barroso
- Wake Forest Baptist Medical Center, Winston-Salem, North Carolina
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Ebrahimi F, Rasizadeh R, Jafari S, Baghi HB. Prevalence of HPV in anal cancer: exploring the role of infection and inflammation. Infect Agent Cancer 2024; 19:63. [PMID: 39696546 DOI: 10.1186/s13027-024-00624-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 11/27/2024] [Indexed: 12/20/2024] Open
Abstract
Anal cancer incidence is rising globally, driven primarily by human papillomavirus (HPV) infection. HPV, especially high-risk types 16 and 18, is considered a necessary cause of anal squamous cell carcinoma. Certain populations like people living with HIV, men who have sex with men, inflammatory bowel disease patients, smokers, and those with compromised immunity face elevated risk. Chronic inflammation facilitates viral persistence, cell transformation, and immune evasion through pathways involving the PD-1/PD-L1 axis. HIV coinfection further increases risk by impairing immune surveillance and epithelial integrity while promoting HPV oncogene expression. Understanding these inflammatory processes, including roles of CD8 + T cells and PD-1/PD-L1, could guide development of immunotherapies against anal cancer. This review summarizes current knowledge on inflammation's role in anal cancer pathogenesis and the interplay between HPV, HIV, and host immune factors.
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Affiliation(s)
- Fatemeh Ebrahimi
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reyhaneh Rasizadeh
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Sajjad Jafari
- Department of Medical Microbiology and Virology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, PO Box 5165665931, Tabriz, Iran.
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Hsu CD, Yu X, Guo F, Adekanmbi V, Kuo YF, Westra J, Berenson AB. Cervical Cancer Screening Utilization among Kidney Transplant Recipients, 2001 to 2018. Cancer Epidemiol Biomarkers Prev 2024; 33:1678-1682. [PMID: 38990185 PMCID: PMC11611682 DOI: 10.1158/1055-9965.epi-24-0225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 04/29/2024] [Accepted: 07/09/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND Kidney transplant recipients (KTR) have elevated risks of cervical precancers and cancers and guidelines recommend more frequent cervical cancer screening exams. However, little is known about current trends in cervical cancer screening in this unique population. We described patterns in the uptake of cervical cancer screening exams among female KTRs and identified factors associated with screening utilization. METHODS This retrospective cohort study included female KTRs between 20 and 65 years old, with Texas Medicare fee-for-service coverage, who received a transplant between January 1, 2001, and December 31, 2017. We determined the cumulative incidence of receiving cervical cancer screening post-transplant using ICD-9, ICD-10, and CPT codes and assessed factors associated with screening utilization, using the Fine and Gray model to account for competing events. Subdistribution hazard models were used to assess factors associated with screening uptake. RESULTS Among 2,653 KTRs meeting the inclusion and exclusion criteria, the 1-, 2-, and 3-year cumulative incidences of initiating a cervical cancer screening exam post-transplant were 31.7% [95% confidence interval (CI), 30.0%-33.6%], 48.0% (95% CI, 46.2%-49.9%), and 58.5% (95% CI, 56.7%-60.3%), respectively. KTRs who were 55 to 64 years old (vs. <45 years old) and those with a higher Charlson Comorbidity Score post-transplant were less likely to receive cervical cancer screening post-transplant. CONCLUSIONS Cervical cancer screening uptake is low in the years immediately following a kidney transplant. IMPACT Our findings highlight a need for interventions to improve cervical cancer screening utilization among kidney transplant recipients. See related In the Spotlight, p. 1554.
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Affiliation(s)
- Christine D. Hsu
- Center for Interdisciplinary Research in Women’s Health, School of Medicine, University of Texas Medical Branch at Galveston, Galveston, TX, USA
- Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, TX, USA
| | - Xiaoying Yu
- Center for Interdisciplinary Research in Women’s Health, School of Medicine, University of Texas Medical Branch at Galveston, Galveston, TX, USA
- Office of Biostatistics, University of Texas Medical Branch at Galveston, Galveston, TX, USA; Department of Biostatistics and Data Science, University of Texas Medical Branch at Galveston, Galveston, TX, USA
| | - Fangjian Guo
- Center for Interdisciplinary Research in Women’s Health, School of Medicine, University of Texas Medical Branch at Galveston, Galveston, TX, USA
- Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, TX, USA
| | - Victor Adekanmbi
- Center for Interdisciplinary Research in Women’s Health, School of Medicine, University of Texas Medical Branch at Galveston, Galveston, TX, USA
- Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, TX, USA
| | - Yong-fang Kuo
- Office of Biostatistics, University of Texas Medical Branch at Galveston, Galveston, TX, USA; Department of Biostatistics and Data Science, University of Texas Medical Branch at Galveston, Galveston, TX, USA
| | - Jordan Westra
- Office of Biostatistics, University of Texas Medical Branch at Galveston, Galveston, TX, USA; Department of Biostatistics and Data Science, University of Texas Medical Branch at Galveston, Galveston, TX, USA
| | - Abbey B. Berenson
- Center for Interdisciplinary Research in Women’s Health, School of Medicine, University of Texas Medical Branch at Galveston, Galveston, TX, USA
- Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, TX, USA
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Miyaji KT, Infante V, Picone CM, Dillner J, Kann H, Eklund C, Levi JE, de Oliveira ACS, Lara AN, Kawakami LS, Tacla M, Castanheira CP, Mayaud P, Sartori AMC. Quadrivalent HPV (4vHPV) vaccine immunogenicity and safety in women using immunosuppressive drugs due to solid organ transplant. Front Cell Infect Microbiol 2024; 14:1452916. [PMID: 39559707 PMCID: PMC11570996 DOI: 10.3389/fcimb.2024.1452916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 08/19/2024] [Indexed: 11/20/2024] Open
Abstract
Introduction Immunocompromised persons are at high risk of persistent Human Papilloma Virus (HPV) infection and associated diseases. Few studies evaluated HPV vaccines in immunocompromised persons. This study aimed to evaluate the quadrivalent HPV vaccine (4vHPV) immunogenicity and safety in solid organ transplant (SOT) recipients, in comparison to immunocompetent women (IC). Methods Open-label clinical trial that enrolled SOT recipients and immunocompetent women aged 18 to 45 years. All participants received three doses of 4vHPV vaccine. Blood samples were drawn for evaluation of immune responses at baseline and one month after the third vaccination. Seroconversion rates and antibody geometric mean concentration (GMC) against HPV 6, 11, 16, 18, 31, 35, 52 and 58 were measured with in-house multiplexed serology assay (xMAP technology). Follow-up for the local and systemic adverse events (AEs) continued for seven days after each vaccination. Severe AEs were evaluated throughout the study. Results 125 SOT and 132 immunocompetent women were enrolled; 105 (84%) SOT and 119 (90%) immunocompetent women completed the study. At baseline, HPV seropositivity was not significantly different between groups. Seroconversion rates were significantly lower in SOT (HPV18, 57%; HPV6 and 16, 69%; and HPV11, 72%) than in immunocompetent women (100% seroconversion to all vaccine types) (p<0.001). Antibody GMCs of all four HPV vaccine types were also significantly lower in SOT (p<0.001). Pain in the injection site and headache were the most frequent adverse event in both groups. Local pain was more frequent in immunocompetent women than in SOT recipients. Rates of other AEs were comparable in both groups. Conclusion 4vHPV vaccine was well-tolerated by SOT recipients. We found strong evidence of lower humoral immune responses to 4vHPV vaccine in SOT compared to immunocompetent women, which strengthen recommendation of routine cervical cancer screening in SOT recipients regardless of HPV vaccination status.
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MESH Headings
- Humans
- Female
- Adult
- Antibodies, Viral/blood
- Papillomavirus Infections/prevention & control
- Papillomavirus Infections/immunology
- Young Adult
- Immunosuppressive Agents/adverse effects
- Organ Transplantation/adverse effects
- Middle Aged
- Adolescent
- Immunogenicity, Vaccine
- Papillomavirus Vaccines/immunology
- Papillomavirus Vaccines/adverse effects
- Papillomavirus Vaccines/administration & dosage
- Immunocompromised Host
- Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/immunology
- Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/adverse effects
- Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/administration & dosage
- Transplant Recipients
- Seroconversion
- Vaccination
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Affiliation(s)
- Karina Takesaki Miyaji
- Departamento de Infectologia e Medicina Tropical da Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo, Brazil
- Clinica de Molestias Infecciosas e Parasitarias do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo, Brazil
- Centro de Referencia para Imunobiológicos Especiais, HCFMUSP, Sao Paulo, Brazil
| | - Vanessa Infante
- Clinica de Molestias Infecciosas e Parasitarias do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo, Brazil
- Centro de Referencia para Imunobiológicos Especiais, HCFMUSP, Sao Paulo, Brazil
| | - Camila Melo Picone
- Departamento de Infectologia e Medicina Tropical da Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo, Brazil
- Clinica de Molestias Infecciosas e Parasitarias do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo, Brazil
| | - Joakim Dillner
- Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
| | - Hanna Kann
- Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
- Department of Microbiology and Immunology, Gothenburg University, Gothenburg, Sweden
| | - Carina Eklund
- Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
| | - José Eduardo Levi
- Laboratório de Investigação Medica – Virologia, Instituto de Medicina Tropical, Sao Paulo, Brazil
| | | | - Amanda Nazareth Lara
- Clinica de Molestias Infecciosas e Parasitarias do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo, Brazil
- Centro de Referencia para Imunobiológicos Especiais, HCFMUSP, Sao Paulo, Brazil
| | | | - Maricy Tacla
- Clínica de Ginecologia, HC-FMUSP, Sao Paulo, Brazil
| | | | - Philippe Mayaud
- Clinical Research Department, London School of Tropical Medicine and Hygiene (LSHTM), London, United Kingdom
| | - Ana Marli Christovam Sartori
- Departamento de Infectologia e Medicina Tropical da Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo, Brazil
- Clinica de Molestias Infecciosas e Parasitarias do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo, Brazil
- Centro de Referencia para Imunobiológicos Especiais, HCFMUSP, Sao Paulo, Brazil
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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10
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Kumar RN, Gorsline CA, Rader T, Boucher HW, Malinis M, Koff A, Harris CE. The pre-transplant evaluation: Considerations for trainees and early career transplant infectious diseases clinician. Transpl Infect Dis 2024; 26:e14326. [PMID: 38967408 DOI: 10.1111/tid.14326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 05/26/2024] [Accepted: 06/13/2024] [Indexed: 07/06/2024]
Abstract
Transplant infectious disease (TID) clinicians are integral to the pre-transplantation evaluation. Pre-transplant evaluations allow clinicians to assess risk factors for latent infections and relevant exposures to potential pathogens, address immunizations, and optimize patients' health and understanding of life after transplant. However, there is not a standardized approach to the pre-transplant evaluation. This article reviews the details of performing successful pre-transplant evaluations, including updated recommendations on available vaccines and contemporary opinions on marijuana use. This resource can be used for teaching with trainees or for early career TID clinicians.
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Affiliation(s)
- Rebecca N Kumar
- Division of Infectious Disease and Tropical Medicine, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Chelsea A Gorsline
- Division of Infectious Disease, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Theodore Rader
- Division of Infectious Diseases and Immunology, UMass Memorial Medical Center, Worcester, Massachusetts, USA
| | - Helen W Boucher
- Division of Geographic Medicine and Infectious Diseases, Tuft University School of Medicine, Boston, Massachusetts, USA
| | - Maricar Malinis
- Division of Infectious Diseases, Vanderbilt University, Nashville, Tennessee, USA
| | - Alan Koff
- Division of Infectious Diseases, University of California, Davis, Sacramento, California, USA
| | - Courtney E Harris
- Division of Infectious Disease, Medical University of South Carolina, Charleston, South Carolina, USA
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11
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Stankiewicz Karita HC, Brickman CE, Chin-Hong P. Anal dysplasia and anal cancer in liver transplant recipients: An urgent call for action for anal cancer screening and further research. Transpl Infect Dis 2024; 26:e14306. [PMID: 38830781 DOI: 10.1111/tid.14306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 05/11/2024] [Indexed: 06/05/2024]
Affiliation(s)
| | - Cristina Elena Brickman
- Department of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Peter Chin-Hong
- Department of Medicine, University of California San Francisco, San Francisco, California, USA
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12
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Jayakrishnan T, Yadav D, Huffman BM, Cleary JM. Immunological Checkpoint Blockade in Anal Squamous Cell Carcinoma: Dramatic Responses Tempered By Frequent Resistance. Curr Oncol Rep 2024; 26:967-976. [PMID: 38861124 DOI: 10.1007/s11912-024-01564-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/28/2024] [Indexed: 06/12/2024]
Abstract
PURPOSE OF REVIEW Squamous cell carcinoma of the anus (SCCA) is an HPV-associated malignancy that has limited treatment options. Immunotherapy has expanded these options and here we review current and emerging immunotherapeutic approaches. RECENT FINDINGS Multiple studies of single-agent anti-PD1/PD-L1 immunotherapy have demonstrated a modest response rate of approximately 10% to 15%. While a minority of patients (~5%) with SCCA experience durable complete responses, most advanced SCCAs are resistant to anti-PD1/PD-L1 monotherapy. Given the need for more broadly effective immunotherapies, novel strategies, such as adaptive cell therapies and therapeutic vaccination, are being explored. To reduce the recurrence risk of localized high-risk SCCA, strategies combining immunotherapy with chemoradiation are also being investigated. While a small subset of patients with SCCA have prolonged responses to PD1-directed immunotherapy, the majority do not derive clinical benefit, and new immunotherapeutic strategies are needed. Better understanding of the immune microenvironment and predictive biomarkers could accelerate therapeutic advances.
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Affiliation(s)
- Thejus Jayakrishnan
- Department of Hematology-Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, USA
| | - Devvrat Yadav
- Department of Internal Medicine, Sinai Hospital of Baltimore, 2401 W Belvedere Ave, Baltimore, MD, 21215, USA
| | - Brandon M Huffman
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - James M Cleary
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
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13
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Ring LL, Larsen HK, Frederiksen K, Hædersdal M, Sørensen SS, Bonde JH, Thomsen LT, Kjær SK. Incidence and clearance of cervical and anal high-risk human papillomavirus in kidney transplant recipients: Results from a Danish prospective clinical study. Am J Transplant 2024; 24:1295-1302. [PMID: 38458364 DOI: 10.1016/j.ajt.2024.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 02/28/2024] [Accepted: 03/04/2024] [Indexed: 03/10/2024]
Abstract
This study investigates the incidence and clearance of cervical and anal high-risk human papillomavirus (hrHPV) infection in kidney transplant recipients (KTRs) compared to immunocompetent controls. During 2016-2017, we enrolled 125 female KTRs and 125 female controls. Liquid-based cervical and anal cytology samples collected at enrollment and follow-up were tested for human papillomavirus (HPV) DNA using the CLART HPV2 test. All participants answered a questionnaire on lifestyle and sexual behavior at both examinations. KTRs had an increased age-adjusted risk of incident cervical hrHPV infection compared to controls (hazard ratio [HR] = 3.6, 95% CI = 1.2-11.2). Probability of cervical hrHPV clearance at 18 months was lower among KTRs (8.3%) than controls (66.7%). There was no statistically significant difference in anal hrHPV incidence between KTRs and controls (HR = 0.9, 95% CI = 0.4-2.0). Clearance of anal hrHPV was similar between KTRs and controls at 18 months. During the total follow-up, a lower anal hrHPV clearance, although not statistically significant, was observed among KTRs (HR = 0.3, 95% CI = 0.06-1.2). KTRs had higher incidence of cervical hrHPV and lower probability of clearance, especially of cervical hrHPV infections, than controls. Our findings support that KTRs are at increased risk of HPV infection and point to the need for targeted HPV prevention strategies, such as cervical cancer screening.
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Affiliation(s)
- Linea Landgrebe Ring
- Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Helle Kiellberg Larsen
- Department of Dermatology and Venereology, Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen, Denmark
| | | | - Merete Hædersdal
- Department of Dermatology and Venereology, Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen, Denmark
| | - Søren Schwartz Sørensen
- Department of Nephrology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Jesper Hansen Bonde
- Department of Pathology, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark
| | | | - Susanne K Kjær
- Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Gynecology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
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14
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Byeman CJ, Harshman LA, Engen RM. Adult and late adolescent complications of pediatric solid organ transplantation. Pediatr Transplant 2024; 28:e14766. [PMID: 38682744 DOI: 10.1111/petr.14766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 03/29/2024] [Accepted: 04/08/2024] [Indexed: 05/01/2024]
Abstract
BACKGROUND There have been over 51 000 pediatric solid organ transplants since 1988 in the United States alone, leading to a growing population of long-term survivors who face complications of childhood organ failure and long-term immunosuppression. AIMS This is an educational review of existing literature. RESULTS Pediatric solid organ transplant recipients are at increased risk for risk for cardiovascular and kidney disease, skin cancers, and growth problems, though the severity of impact may vary by organ type. Pediatric recipients often are able to complete schooling, maintain a job, and form family and social networks in adulthood, though at somewhat lower rates than the general population, but face additional challenges related to neurocognitive deficits, mental health disorders, and discrimination. CONCLUSIONS Transplant centers and research programs should expand their focus to include long-term well-being. Increased collaboration between pediatric and adult transplant specialists will be necessary to better understand and manage long-term complications.
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Affiliation(s)
- Connor J Byeman
- University of Iowa Carver College of Medicine, Iowa, Iowa, USA
| | - Lyndsay A Harshman
- Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa, Iowa, USA
| | - Rachel M Engen
- University of Wisconsin Madison, Madison, Wisconsin, USA
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15
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Kao CM, Michaels MG. Approach to vaccinating the pediatric solid organ transplant candidate and recipient. Front Pediatr 2023; 11:1271065. [PMID: 38027303 PMCID: PMC10663229 DOI: 10.3389/fped.2023.1271065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 10/27/2023] [Indexed: 12/01/2023] Open
Abstract
Solid organ transplantation (SOT) candidates and recipients are at increased risk for morbidity and mortality from vaccine-preventable infections. Children are at particular risk given that they may not have completed their primary immunization series at time of transplant or have acquired natural immunity to pathogens from community exposures. Multiple society guidelines exist for vaccination of SOT candidate and recipients, although challenges remain given limited safety and efficacy data available for pediatric SOT recipients, particularly for live-vaccines. After transplant, individual patient nuances regarding exposure risks and net state of immunosuppression will impact timing of immunizations. The purpose of this review is to provide readers with a concise, practical, expert-opinion on the approach to vaccinating the SOT candidate and recipient and to supplement existing guidelines. In addition, pediatric-specific knowledge gaps in the field and future research priorities will be highlighted.
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Affiliation(s)
- Carol M. Kao
- Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, United States
| | - Marian G. Michaels
- Department of Pediatrics and Surgery, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, United States
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16
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Albuquerque A, Cappello C, Stirrup O, Selinger CP. Anal High-risk Human Papillomavirus Infection, Squamous Intraepithelial Lesions, and Anal Cancer in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Crohns Colitis 2023; 17:1228-1234. [PMID: 36929761 DOI: 10.1093/ecco-jcc/jjad045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Indexed: 03/18/2023]
Abstract
BACKGROUND Ulcerative colitis [UC] and Crohn's disease [CD] can be associated with severe comorbidities, namely opportunistic infections and malignancies. We present the first systematic review and meta-analysis evaluating the burden of anal human papillomavirus disease in patients with UC and CD. METHODS PubMed, Web of Science, and Scopus were searched until November 2022. Meta-analyses were performed using random effects models. The protocol was recorded at PROSPERO register with the number CRD42022356728. RESULTS Six studies, including 78 711 patients with UC with a total follow-up of 518 969 person-years, described the anal cancer incidence rate. For anal cancer incidence rate in CD, six studies were selected, including 56 845 patients with a total follow-up of 671 899 person-years. The incidence of anal cancer was 10.2 [95% CI 4.3 - 23.7] per 100 000 person-years in UC and 7.7 [3.5 - 17.1] per 100 000 person-years in CD. A subgroup analysis of anal cancer in perianal CD, including 7105 patients, was calculated with incidence of 19.6 [12.2 - 31.6] per 100 000 person-years [three studies included]. Few studies described prevalence of anal cytological abnormalities [four studies including 349 patients] or high-risk human papillomavirus [three studies including 210 patients], with high heterogeneity. Prevalence of cytological abnormalities or high-risk human papillomavirus was not associated with pharmacological immunosuppression in the studies included. CONCLUSION The incidence of anal cancer is higher in UC than in CD, with the exception of perianal CD. There are limited and heterogeneous data on anal high-risk human papillomavirus infection and squamous intraepithelial lesions prevalence in this population.
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Affiliation(s)
- Andreia Albuquerque
- Gastroenterology Department, Fernando Pessoa Teaching Hospital, Porto, Portugal
- Precancerous Lesions and Early Cancer Management Research Group RISE@CI-IPO [Health Research Network], Portuguese Oncology Institute of Porto [IPO-Porto], Porto, Portugal
| | - Carmelina Cappello
- Homerton Anogenital Neoplasia Service, Homerton University Hospital, London, UK
| | - Oliver Stirrup
- Institute for Global Health, University College London, London, UK
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17
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Jones-Pauley M, Kodali S, Basra T, Victor DW. Women's health issues in solid organ transplantation: Breast and gynecologic cancers in the post-transplant population. World J Transplant 2023; 13:129-137. [PMID: 37388393 PMCID: PMC10303419 DOI: 10.5500/wjt.v13.i4.129] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 04/19/2023] [Accepted: 05/31/2023] [Indexed: 06/16/2023] Open
Abstract
The success of solid organ transplant has steadily improved which has led to a unique set of post-transplant issues. The rates of de novo cancer in the solid organ transplant recipient population are higher than those in the general population. There is growing evidence that breast and gynecologic cancers may have a higher mortality rate in post-transplant patients. Cervical and vulvovaginal cancers specifically have a significantly higher mortality in this population. Despite this increased mortality risk, there is currently no consistent standard in screening and identifying these cancers in post-transplant patients. Breast, ovarian and endometrial cancers do not appear to have significantly increased incidence. However, the data on these cancers remains limited. Further studies are needed to determine if more aggressive screening strategies would be of benefit for these cancers. Here we review the cancer incidence, mortality risk and current screening methods associated with breast and gynecologic cancers in the post-solid organ transplant population.
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Affiliation(s)
- Michelle Jones-Pauley
- Department of Gastroenterology, Houston Methodist Hospital, Houston, TX 77008, United States
| | - Sudha Kodali
- Department of Transplant Hepatology, Houston Methodist Hospital, Houston, TX 77030, United States
| | - Tamneet Basra
- Department of Transplant Hepatology, Houston Methodist Hospital, Houston, TX 77030, United States
| | - David W Victor
- Department of Transplant Hepatology, Houston Methodist Hospital, Houston, TX 77030, United States
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18
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Ley D, Musto J. Immunizations in liver transplant candidates. Clin Liver Dis (Hoboken) 2023; 21:151-154. [PMID: 37937049 PMCID: PMC10627590 DOI: 10.1097/cld.0000000000000031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 01/09/2023] [Indexed: 11/09/2023] Open
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Hewavisenti RV, Arena J, Ahlenstiel CL, Sasson SC. Human papillomavirus in the setting of immunodeficiency: Pathogenesis and the emergence of next-generation therapies to reduce the high associated cancer risk. Front Immunol 2023; 14:1112513. [PMID: 36960048 PMCID: PMC10027931 DOI: 10.3389/fimmu.2023.1112513] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 02/03/2023] [Indexed: 03/09/2023] Open
Abstract
Human papillomavirus (HPV), a common sexually transmitted virus infecting mucosal or cutaneous stratified epithelia, is implicated in the rising of associated cancers worldwide. While HPV infection can be cleared by an adequate immune response, immunocompromised individuals can develop persistent, treatment-refractory, and progressive disease. Primary immunodeficiencies (PIDs) associated with HPV-related disease include inborn errors of GATA, EVER1/2, and CXCR4 mutations, resulting in defective cellular function. People living with secondary immunodeficiency (e.g. solid-organ transplants recipients of immunosuppression) and acquired immunodeficiency (e.g. concurrent human immunodeficiency virus (HIV) infection) are also at significant risk of HPV-related disease. Immunocompromised people are highly susceptible to the development of cutaneous and mucosal warts, and cervical, anogenital and oropharyngeal carcinomas. The specific mechanisms underlying high-risk HPV-driven cancer development in immunocompromised hosts are not well understood. Current treatments for HPV-related cancers include surgery with adjuvant chemotherapy and/or radiotherapy, with clinical trials underway to investigate the use of anti-PD-1 therapy. In the setting of HIV co-infection, persistent high-grade anal intraepithelial neoplasia can occur despite suppressive antiretroviral therapy, resulting in an ongoing risk for transformation to overt malignancy. Although therapeutic vaccines against HPV are under development, the efficacy of these in the setting of PID, secondary- or acquired- immunodeficiencies remains unclear. RNA-based therapeutic targeting of the HPV genome or mRNA transcript has become a promising next-generation therapeutic avenue. In this review, we summarise the current understanding of HPV pathogenesis, immune evasion, and malignant transformation, with a focus on key PIDs, secondary immunodeficiencies, and HIV infection. Current management and vaccine regimes are outlined in relation to HPV-driven cancer, and specifically, the need for more effective therapeutic strategies for immunocompromised hosts. The recent advances in RNA-based gene targeting including CRISPR and short interfering RNA (siRNA), and the potential application to HPV infection are of great interest. An increased understanding of both the dysregulated immune responses in immunocompromised hosts and of viral persistence is essential for the design of next-generation therapies to eliminate HPV persistence and cancer development in the most at-risk populations.
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Affiliation(s)
- Rehana V. Hewavisenti
- Immunovirology and Pathogenesis Program, The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia
| | - Joshua Arena
- Immunovirology and Pathogenesis Program, The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia
- UNSW RNA Institute, The University of New South Wales, Sydney, NSW, Australia
| | - Chantelle L. Ahlenstiel
- Immunovirology and Pathogenesis Program, The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia
- UNSW RNA Institute, The University of New South Wales, Sydney, NSW, Australia
| | - Sarah C. Sasson
- Immunovirology and Pathogenesis Program, The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia
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Kristiansen S, Bjartling C, Torbrand C, Grelaud D, Lindström M, Svensson Å, Forslund O. Increased prevalence of human papillomavirus in fresh tissue from penile cancers compared to non-malignant penile samples: a case-control study. BMC Cancer 2022; 22:1227. [PMID: 36443686 PMCID: PMC9703753 DOI: 10.1186/s12885-022-10324-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 11/16/2022] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND HPV has been detected in approximately 50% of invasive penile cancers but with a large span between 24 and 89%, most likely due to different types of tumors and various methods for HPV analysis. Most studies of HPV in penile cancer have been performed using paraffin-embedded tissue, argued to be at risk for contaminated HPV analysis. Viral activity of HPV, by the use of HPV mRNA expression is well studied in cervical cancer, but seldom studied in penile cancer. The aim was to determine prevalence of HPV types in fresh tissue of penile cancers compared to non-malignant age-matched penile controls. Additional aims were to analyze the viral expression and copy numbers of HPV16-positive tumors and 10 mm adjacent to the tumor. METHODS Fresh tissue from penile cancer cases was biopsied inside the tumor and 10 mm outside the tumor. Controls were males circumcised for non-malignant reasons, biopsied at surgery. PCR and Luminex assays were used for identification of HPV types. HPV16-positive samples were investigated for copy numbers and expression of HPV16-mRNA. RESULTS Among tumors (n = 135) and age-matched controls (n = 105), HPV was detected in 38.5% (52/135) and 11.4% (12/105), respectively (p < 0.001), adjusted odds ratio 12.8 (95% confidence interval 4.9-33.6). High-risk HPV types were found in 35.6% (48/135) of tumors and 4.8% (5/105) of controls (p < 0.001). Among tumors and controls, HPV16 was present in 27.4% (37/135) and 1% (1/105), respectively (p < 0.001). Among HPV16-positive penile cancers, mean HPV16 viral copy/cell was 74.4 (range 0.00003-725.4) in the tumor and 1.6 (range 0.001-14.4) 10 mm adjacent from the tumor. HPV16-mRNA analysis of the tumors and 10 mm adjacent from the tumors demonstrated viral activity in 86.5% (32/37) and 21.7% (5/23), respectively. CONCLUSIONS The prevalence of HPV was significantly higher in penile cancer (38.5%) than among age-matched non-malignant penile samples (11.4%). HPV16 predominates (27.4%) in penile tumors. HPV16 expression was more common in penile cancer than in adjacent healthy tissue, strongly suggesting an etiological role for HPV16 in the development of penile cancer.
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Affiliation(s)
- Sinja Kristiansen
- grid.4514.40000 0001 0930 2361Department of Dermatology and Venereology, Lund University, Skane University Hospital, Jan Waldenströmsgata 16, 214 28 Malmö, Sweden
| | - Carina Bjartling
- grid.4514.40000 0001 0930 2361Department of Obstetrics and Gynecology, Lund University, Skane University Hospital, Malmö, Sweden
| | - Christian Torbrand
- grid.413823.f0000 0004 0624 046XLund University, Department of Urology, Helsingborg Hospital, Helsingborg, Sweden ,grid.4514.40000 0001 0930 2361Lund University, Institution of Translational Medicine, Malmö, Sweden
| | - Diane Grelaud
- grid.411843.b0000 0004 0623 9987Department of Pathology, Skane University Hospital and Regional Laboratories, Malmö, Sweden
| | - Martin Lindström
- grid.411843.b0000 0004 0623 9987Department of Pathology, Skane University Hospital and Regional Laboratories, Malmö, Sweden
| | - Åke Svensson
- grid.4514.40000 0001 0930 2361Department of Dermatology and Venereology, Lund University, Skane University Hospital, Jan Waldenströmsgata 16, 214 28 Malmö, Sweden
| | - Ola Forslund
- grid.4514.40000 0001 0930 2361Lund University, Department of Medical Microbiology, Laboratory Medicine, Lund, Sweden ,grid.426217.40000 0004 0624 3273Clinical Microbiology, Infection Prevention and Control, Office for Medical Services Region Skane, Kristianstad, Sweden
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21
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Garcia M, McGillicuddy C, Rodriguez EM, Attwood K, Schweitzer J, Coley S, Rokitka D, Schlecht NF. Human papillomavirus vaccination uptake among childhood cancer survivors in Western New York. Pediatr Blood Cancer 2022; 69:e29962. [PMID: 36094384 PMCID: PMC9529834 DOI: 10.1002/pbc.29962] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 08/11/2022] [Accepted: 08/12/2022] [Indexed: 11/11/2022]
Abstract
INTRODUCTION The risk of human papillomavirus (HPV)-associated cancers is significantly higher among survivors of a childhood cancer compared to the general population. Despite this, their HPV vaccine uptake rates are lower. We examined factors related to HPV vaccine uptake among childhood cancer survivors from Western New York over 13 years following the introduction of HPV vaccines. METHODS Retrospective review of patients diagnosed with invasive or noninvasive cancerous conditions at age 9 or younger treated at Roswell Park Oishei Children's Cancer and Blood Disorder Program. We matched vaccine date information for patients aged 9-26 years between 2006 and 2020 from the New York State Immunization Information System. Demographic and cancer-related information was abstracted from electronic medical records. Cumulative vaccine uptake was assessed by Kaplan-Meier and Cox proportional hazards regression models. RESULTS A total of 284 patients were included in the analyses. Most were non-Hispanic/White (80.3%) and resided in a metropolitan area (81.7%). Approximately half had leukemia or lymphoma (54.9%), and most received chemotherapy. Females were more likely to initiate the HPV vaccine and did so sooner (median = 5.5 years) than males (median = 5.7 years; log-rank p = .301). Patients who were older at vaccine eligibility and males who received blood product transfusions were significantly less likely to initiate the HPV vaccine. CONCLUSION While rates of HPV vaccine initiation have been increasing with time among childhood cancer survivors, they remain low overall, with differences seen by treatment and diagnosis. Our findings support the need for further research to optimize HPV vaccine delivery in cancer care.
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Affiliation(s)
- Melany Garcia
- Roswell Park Comprehensive Cancer Center, Cancer Prevention and Control, Buffalo, NY, United States of America
| | - Cailey McGillicuddy
- Roswell Park Comprehensive Cancer Center, Cancer Prevention and Control, Buffalo, NY, United States of America
| | - Elisa M. Rodriguez
- Roswell Park Comprehensive Cancer Center, Cancer Prevention and Control, Buffalo, NY, United States of America
| | - Kristopher Attwood
- Roswell Park Comprehensive Cancer Center, Biostatistics and Bioinformatics, Buffalo, NY, United States of America
| | - Jennifer Schweitzer
- Roswell Park Comprehensive Cancer Center, Clinical Research Services, Buffalo, NY, United States of America
| | - Scott Coley
- New York State Department of Health, Bureau of Immunization, NY, United States of America
| | - Denise Rokitka
- Department of Pediatrics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States of America
| | - Nicolas F. Schlecht
- Roswell Park Comprehensive Cancer Center, Cancer Prevention and Control, Buffalo, NY, United States of America
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Nailescu C, Ermel AC, Shew ML. Human papillomavirus-related cancer risk for solid organ transplant recipients during adult life and early prevention strategies during childhood and adolescence. Pediatr Transplant 2022; 26:e14341. [PMID: 35808949 DOI: 10.1111/petr.14341] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 05/03/2022] [Accepted: 05/27/2022] [Indexed: 11/27/2022]
Abstract
Malignancies are among the top three causes of patient death in pediatric and adult kidney transplant (KT) recipients. Solid organ transplant (SOT) recipients, including KT individuals, experience more cancer compared with the general population, including human papillomavirus (HPV)-related anogenital and oropharyngeal cancers. This article describes the epidemiology, pathophysiology and natural history of the HPV infection in both the general population and in SOT recipients, as well as its role in the development of HPV-related pre-cancerous lesions and cancers. Emphasis is given to the primary prevention strategy, HPV vaccination in SOT recipients, and its particularities compared with the general population. Secondary prevention strategies in SOT recipients are discussed and compared with the general population, highlighting cervical cancer screening needs within SOT populations. The article emphasizes how these primary and secondary HPV prevention strategies applied during childhood and adolescence by the pediatric transplant professionals, can lower the burden of HPV-related cancers for SOT recipients in subsequent years, during their adult life.
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Affiliation(s)
- Corina Nailescu
- Section of Pediatric Nephrology and Hypertension, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Aaron C Ermel
- Section of Infectious Diseases, Department of Medicine, Indiana University Health University Hospital, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Marcia L Shew
- Section of Adolescent Medicine, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana, USA
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23
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Approaches to pretransplant vaccination. Curr Opin Organ Transplant 2022; 27:277-284. [PMID: 36354254 DOI: 10.1097/mot.0000000000000994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
PURPOSE OF REVIEW The aim of this study was to summarize new data and perspectives in pretransplant vaccination, with a particular focus on COVID-19 vaccination and vaccination requirements. RECENT FINDINGS Pretransplant vaccination produces superior markers of immunity and is expected to have greater clinical benefit, compared with posttransplant vaccination. As such, efforts are underway to identify and characterize barriers to pretransplant vaccination, with a particular focus on COVID-19 vaccine hesitancy. Unfortunately, vaccine hesitancy is common in transplant patients, often motivated by individual side effect and safety concerns. COVID-19 vaccination requirements have been implemented in some centres, informed by ethical principles, including beneficence, utility and justice. SUMMARY Barriers to pretransplant vaccination can be understood in three categories: hard stops, including issues of vaccine availability, eligibility, safety and feasibility; soft stops, including issues of convenience, prioritization and care coordination; and volitional stops related to vaccine hesitancy and refusal. All of these barriers present opportunities for improvement based on recent data.
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24
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Olczak P, Matsui K, Wong M, Alvarez J, Lambert P, Christensen ND, Hu J, Huber B, Kirnbauer R, Wang JW, Roden RBS. RG2-VLP: a Vaccine Designed to Broadly Protect against Anogenital and Skin Human Papillomaviruses Causing Human Cancer. J Virol 2022; 96:e0056622. [PMID: 35703545 PMCID: PMC9278150 DOI: 10.1128/jvi.00566-22] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 05/20/2022] [Indexed: 12/20/2022] Open
Abstract
The family of human papillomaviruses (HPV) includes over 400 genotypes. Genus α genotypes generally infect the anogenital mucosa, and a subset of these HPV are a necessary, but not sufficient, cause of cervical cancer. Of the 13 high-risk (HR) and 11 intermediate-risk (IR) HPV associated with cervical cancer, genotypes 16 and 18 cause 50% and 20% of cases, respectively, whereas HPV16 dominates in other anogenital and oropharyngeal cancers. A plethora of βHPVs are associated with cutaneous squamous cell carcinoma (CSCC), especially in sun-exposed skin sites of epidermodysplasia verruciformis (EV), AIDS, and immunosuppressed patients. Licensed L1 virus-like particle (VLP) vaccines, such as Gardasil 9, target a subset of αHPV but no βHPV. To comprehensively target both α- and βHPVs, we developed a two-component VLP vaccine, RG2-VLP, in which L2 protective epitopes derived from a conserved αHPV epitope (amino acids 17 to 36 of HPV16 L2) and a consensus βHPV sequence in the same region are displayed within the DE loop of HPV16 and HPV18 L1 VLP, respectively. Unlike vaccination with Gardasil 9, vaccination of wild-type and EV model mice (Tmc6Δ/Δ or Tmc8Δ/Δ) with RG2-VLP induced robust L2-specific antibody titers and protected against β-type HPV5. RG2-VLP protected rabbits against 17 αHPV, including those not covered by Gardasil 9. HPV16- and HPV18-specific neutralizing antibody responses were similar between RG2-VLP- and Gardasil 9-vaccinated animals. However, only transfer of RG2-VLP antiserum effectively protected naive mice from challenge with all βHPVs tested. Taken together, these observations suggest RG2-VLP's potential as a broad-spectrum vaccine to prevent αHPV-driven anogenital, oropharyngeal, and βHPV-associated cutaneous cancers. IMPORTANCE Licensed preventive HPV vaccines are composed of VLPs derived by expression of major capsid protein L1. They confer protection generally restricted to infection by the αHPVs targeted by the up-to-9-valent vaccine, and their associated anogenital cancers and genital warts, but do not target βHPV that are associated with CSCC in EV and immunocompromised patients. We describe the development of a two-antigen vaccine protective in animal models against known oncogenic αHPVs as well as diverse βHPVs by incorporation into HPV16 and HPV18 L1 VLP of 20-amino-acid conserved protective epitopes derived from minor capsid protein L2.
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Affiliation(s)
- Pola Olczak
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA
| | | | - Margaret Wong
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Jade Alvarez
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Paul Lambert
- McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Neil D. Christensen
- The Jake Gittlen Laboratories for Cancer Research, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, USA
- Department of Pathology, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, USA
| | - Jiafen Hu
- The Jake Gittlen Laboratories for Cancer Research, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, USA
- Department of Pathology, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, USA
| | - Bettina Huber
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Reinhard Kirnbauer
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
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Rolak S, Said A, German R, Hayney MS, Caldera F. Optimizing Immunization Strategies in Adult Patients With Chronic Liver Disease and Liver Transplant Recipients. Gastroenterol Hepatol (N Y) 2022; 18:196-206. [PMID: 35505940 PMCID: PMC9053492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Patients with chronic liver disease (CLD) and liver transplant recipients are at increased risk for infections from vaccine-preventable diseases. Gastroenterologists and hepatologists should assess patient immunization history, and necessary vaccinations should be given as soon as possible. Vaccines demonstrate superior immunogenicity when given earlier in the course of liver disease and prior to transplant. This article summarizes recommendations from the Advisory Committee on Immunization Practices for vaccinations in patients with CLD and liver transplant recipients, and includes a discussion of the influenza, herpes zoster, hepatitis A, hepatitis B, pneumococcal, human papillomavirus, and COVID-19 vaccines.
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Affiliation(s)
- Stacey Rolak
- Department of Internal Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
| | - Adnan Said
- Department of Medicine, Division of Gastroenterology and Hepatology, School of Medicine & Public Health, University of Wisconsin–Madison, Madison, Wisconsin
| | - Rita German
- Department of Medicine, Division of Gastroenterology and Hepatology, School of Medicine & Public Health, University of Wisconsin–Madison, Madison, Wisconsin
| | - Mary S. Hayney
- School of Pharmacy, University of Wisconsin–Madison, Madison, Wisconsin
| | - Freddy Caldera
- Department of Medicine, Division of Gastroenterology and Hepatology, School of Medicine & Public Health, University of Wisconsin–Madison, Madison, Wisconsin
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26
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Thornton C, Somayaji R, Chu A, Parkins MD. Human papillomavirus (HPV) and cervical dysplasia in adult female cystic fibrosis (CF) lung transplant recipients. Thorax 2022; 77:625-627. [PMID: 35121654 DOI: 10.1136/thoraxjnl-2021-218461] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 01/10/2022] [Indexed: 11/03/2022]
Abstract
Human papillomavirus (HPV) is the principal risk factor for cervical cancer. Transplant recipients are at a disproportionate risk of HPV complications. We conducted a single-centre, retrospective study of adult female cystic fibrosis (CF) lung transplant recipients between 2008 and 2021. We observed 12 of 34 (35.3%) with ≥1 abnormal pap smear (median age: 26.7 years). Complications included refractory anogenital warts (n=3), vulvectomy (n=2) and cervical cancer (n=4), with two deaths from metastatic disease. None with HPV morbidity was vaccinated. Lung transplant recipients had greater odds of cervical dysplasia relative to controls (OR, 3.98; 95% CI 1.17 to 11.82). CF care providers must prioritise HPV vaccination to attenuate potential future morbidity and mortality.
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Affiliation(s)
- Christina Thornton
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Ranjani Somayaji
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.,Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Angel Chu
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada
| | - Michael D Parkins
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada .,Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada
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27
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Borin A, Violi P, Eccher A, Zaza G, Carraro A. Carcinogenesis and Cancer Progression in De Novo Anal Squamous Cell Carcinoma After Organ Transplantation: A Systematic Review. EXP CLIN TRANSPLANT 2022; 20:122-129. [PMID: 35282809 DOI: 10.6002/ect.2021.0412] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Our aim was to perform a comprehensive literature review on the pathogenesis of squamous anal cancerin patients after solid-organ transplant. Medical databases were consulted until June 1, 2020, for potentially relevant publications.All studies on pathogenesis of de novo anal squamous cell carcinoma in solid-organ transplant recipients were included. Two researchers independently performed study selection, quality assessment, and data extraction and analysis. Twenty-one studies were included.None ofthe selected papers had been solely focused on carcinogenesis. Most ofthe studies identified human papillomavirus infection and immunosuppression to be significantly correlated with the development of de novo anal cancer in adult solid organ transplant recipients. CD4+ T-cell depletion and inactivation oftumor suppressor pathways were mainly implicated. All solid-organ transplant recipients, especially those who were human papillomavirus positive, were shown to be at increased risk for the development of posttransplant anal cancer. Further studies are needed to determine the specific mechanisms of pathogenesis according to different solid-organ transplant populations.
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Affiliation(s)
- Alex Borin
- From the Department of General Surgery and Dentistry, Liver Transplant Unit, University and Hospital Trust of Verona, Verona, Italy
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28
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New Insights into the Epidemiology of Vulvar Cancer: Systematic Literature Review for an Update of Incidence and Risk Factors. Cancers (Basel) 2022; 14:cancers14020389. [PMID: 35053552 PMCID: PMC8773873 DOI: 10.3390/cancers14020389] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 12/22/2021] [Accepted: 01/07/2022] [Indexed: 12/20/2022] Open
Abstract
Simple Summary Vulvar cancer incidence data were sought from official sources (WHO Cancer Incidence in Five Continents) and studies reporting comparable data. With respect to risk factors, a systematic PubMed search of articles published since 1980 identified 69 original cohort and case-control studies. Information was extracted using a PRISMA predesigned data collection form. Recent advances have provided further evidence in support of the carcinogenic model centred on human papillomavirus infection with different defects of the immune function. Conversely, the model centred on the role of vulvar lichen sclerosus and the often-associated differentiated vulva intraepithelial neoplasia has continued to be understudied. Abstract The aim of this review was an update of vulvar cancer incidence rates and trends and of all known and putative risk factors for the disease. The most recent incidence data were sought from official sources (WHO Cancer Incidence in Five Continents). To obtain an estimate of time trends in some areas, we compared data from Cancer Incidence in Five Continents with the few available studies that measured incidence using comparable methods. With respect to risk factors, a systematic PubMed search identified 1585 relevant articles published between 1980 and 2021. Abstracts and full texts were screened. Sixty-nine eligible original cohort and case-control studies were selected. Information was extracted using a PRISMA predesigned form. Nineteen risk factors, or risk factor categories, were investigated by two or more original studies. Solitary, unreplicated studies addressed the putative role of eight more factors. Recent advances have provided further evidence supporting the carcinogenic model centred on human papillomavirus infection with different defects of the immune function. Conversely, the model centred on the role of vulvar lichen sclerosus and the often associated differentiated vulvar intraepithelial neoplasia has continued to be epidemiologically understudied. More research on the association between these two conditions and vulvar cancer is a priority.
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29
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Egloff C, Mergui JL, Uzan C, Canlorbe G. [Management of HPV-induced cervical lesions in immunosuppressed patients - Review of the literature]. GYNECOLOGIE, OBSTETRIQUE, FERTILITE & SENOLOGIE 2022; 50:82-92. [PMID: 34768006 DOI: 10.1016/j.gofs.2021.10.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 10/21/2021] [Accepted: 10/23/2021] [Indexed: 06/13/2023]
Abstract
INTRODUCTION Current French recommendations for the management of cervical lesions related to human papilloma virus (HPV) infection are limited to general population. Patients who are immunocompromised appear to be at increased risk of induced HPV lesions. The objective of this review is to summarize the various existing data about risk of induced HPV lesions in immunocompromised patients to specify the management. METHODS The Medline database was searched through the Pubmed portal, as well as the recommendations of various international learned societies. RESULTS Situations with an increased risk are regardless of treatment: Human Immunodeficiency Virus (HIV) infection, transplants, lupus. Patients with chronic inflammatory bowel disease (IBD) and rheumatoid arthritis are at increased risk only when immunosuppressive therapy is required. Screening for dysplasic intraepithelial lesions in HIV+ patients should be more sustained than in the general population. Due to lack of data, recommendations for other conditions have been extrapolated from the management of HIV+ patients. HPV vaccination is effective in these populations, particularly at times when the immune system is the most effective. DISCUSSION Identified immunocompromised populations are at higher risk of induced HPV lesions due to an incomplete immune response and should be screened on a sustained basis. In addition, HPV vaccination should be encouraged.
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Affiliation(s)
- C Egloff
- AP-HP, hôpital Pitié-Salpêtrière, Sorbonne Université, service de chirurgie et cancérologie gynécologique et mammaire, 47-83, boulevard de l'Hôpital, 75013 Paris, France
| | - J-L Mergui
- AP-HP, hôpital Pitié-Salpêtrière, Sorbonne Université, service de chirurgie et cancérologie gynécologique et mammaire, 47-83, boulevard de l'Hôpital, 75013 Paris, France; Société Française de Colposcpopie et de Pathologie Cervico-Vaginale (SFCPCV)
| | - C Uzan
- AP-HP, hôpital Pitié-Salpêtrière, Sorbonne Université, service de chirurgie et cancérologie gynécologique et mammaire, 47-83, boulevard de l'Hôpital, 75013 Paris, France; Sorbonne Universié, Inserm UMR S938 « Biologie et thérapeutique des cancers », Paris, France; AP-HP, institut universitaire de cancérologie, Sorbonne Université (IUC AP-HP.SU), Paris, France
| | - G Canlorbe
- AP-HP, hôpital Pitié-Salpêtrière, Sorbonne Université, service de chirurgie et cancérologie gynécologique et mammaire, 47-83, boulevard de l'Hôpital, 75013 Paris, France; Société Française de Colposcpopie et de Pathologie Cervico-Vaginale (SFCPCV); Sorbonne Universié, Inserm UMR S938 « Biologie et thérapeutique des cancers », Paris, France; AP-HP, institut universitaire de cancérologie, Sorbonne Université (IUC AP-HP.SU), Paris, France.
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30
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Ejaz M, Mubarak M, Ali TS, Andersson S, Ekström AM. Human papillomavirus-associated anal squamous intraepithelial lesions in men who have sex with men and transgender women living with and without HIV in Karachi Pakistan: implications for screening and prevention. BMC Infect Dis 2021; 21:1163. [PMID: 34789177 PMCID: PMC8597180 DOI: 10.1186/s12879-021-06850-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 11/01/2021] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Anal squamous intraepithelial lesions (ASIL), strongly related to human papilloma virus (HPV) infection, is more prevalent among men who have sex with men (MSM). However, no such data are available for Pakistan yet, and neither HPV vaccination nor anal-cytology screening is implemented in Pakistan. The purpose of this first ever study was to assess the prevalence of HPV-related anal cytological abnormalities among MSM and transgender women living with and without HIV infection in Pakistan. METHODS We conducted a cross-sectional study from March 2016 to November 2017 at sexual health centers run by the Perwaaz Trust and the National AIDS Control Program in Karachi. The study enrolled MSM and transgender women aged greater-than-and-equal-to-18-years who reported anal sex in the preceding 6 months. We collected two anal samples for liquid-based cytology and HPV type testing by PCR, and socio-demographic and behavioral data were collected through face-to face interviews. ASIL and its associations with biological and behavioral risk factors were analyzed through Cox regression for prevalence ratios (PR) and corresponding 95% confidence intervals (CIs). RESULTS Out of 271 qualifying participants, 79% were MSM and 21% transgender women. The mean age was 28.8 (± 8) years. Almost 35% (93/271) of the study population had ASIL detected, ASIL was significantly more common among participants living with HIV than in HIV negative ((50/118) 42.4%; vs. (43/153) 28.1%) (p ≤ 0.001). Among ASIL, 66% (61/93) had low-grade squamous intraepithelial lesions (LSIL), and 3.6% (3/93) had high-grade squamous intraepithelial lesions (HSIL). The overall, HPV16 positivity was 35.5% (33/93) among all abnormal anal lesions and all 3 HSIL were HPV16 positive, however, HPV16 positivity could show its association with ASIL detection in univariate model only (PRcrude: 2.11(1.39-3.18)). Moreover, any HR-HPV type (PR 3.04; 95% CI 1.75-5.26), concurrent sexually transmitted infection (STI) (2.13; (1.28-3.55)) and HIV + /HPV + coinfection (1.75; (1.07-2.88)) remained independently associated with ASIL in the multivariate model. CONCLUSIONS Abnormal anal cytology among MSM and transgender is prevalent enough to consider optimal screening regimens. Further studies are required to see if periodic anal cytology can be made part of HIV care and treatment programs among MSM in Pakistan.
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Affiliation(s)
- Muslima Ejaz
- Department of Global Public Health, Global and Sexual Health Research Group, Karolinska Institutet, Widerströmska Huset, Tomtebodavägen 18A, 171 77, Stockholm, Sweden.
- Department of Community Health Sciences, Aga Khan University (AKU), Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan.
| | - Muhammad Mubarak
- Department of Cytology and Histopathology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | | | - Sören Andersson
- Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Anna Mia Ekström
- Department of Global Public Health, Global and Sexual Health Research Group, Karolinska Institutet, Widerströmska Huset, Tomtebodavägen 18A, 171 77, Stockholm, Sweden
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Keenan RA, Haroon U, Ryan P, Harrington B, Jones A, Aboelmagd M, Connolly S, O'Mally KJ, Galvin D, Hegarty N. Management of Urological Malignancy in Heart and Lung Transplant Recipients: An Irish National Cohort Study. EXP CLIN TRANSPLANT 2021; 19:1069-1075. [PMID: 34641776 DOI: 10.6002/ect.2021.0206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Following the first hearttransplantin Ireland in 1985, there have been almost 700 deceased donor heart and lung transplants carried out in Ireland at a single institution. In this retrospective study, our aim was to assess the incidence and management of urological malignancies arising in this national cohort. MATERIALS AND METHODS Our retrospective analysis included all heart and lung transplant recipients identified as having a urological malignancy. Primary outcome variables included incidence, management, and clinical outcomes following cancer diagnosis. RESULTS A total of 28 patients (4.1%) had radiologically or histologically confirmed urological malignancies. Fourteen patientswere diagnosedwith prostate cancer, with 13 who underwent radical treatment. Eight renal cell carcinomas were diagnosed in heart transplant recipients, with 5 who underwent nephrectomies. Two bladder cancers and 1 uppertract urothelial carcinoma were diagnosed and managed with endoscopic resection, radiotherapy, and nephroureterectomy, respectively. Two patients were diagnosed with penile squamous cell carcinoma and managed with radical surgery and lymph node dissection/sampling, with 1 patient receiving adjuvant chemoradiotherapy. CONCLUSIONS Urological malignancies are not common in heart and lung transplant recipients; however, standard management options can be safely used, including radical surgery. Prospective monitoring of these patients and potential considerations for screening should be maintained.
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Affiliation(s)
- Robert A Keenan
- >From the Department of Urology, Mater Misericordiae University Hospital, Dublin, Ireland
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Affiliation(s)
- Andreia Albuquerque
- CINTESIS-Center for Health Technology and Services Research, Medical Research Center, University of Porto, Portugal
- Gastroenterology Department, Central Lisbon University Hospital Centre, Lisbon, Portugal
| | - Pedro Vieira Baptista
- Hospital Lusíadas Porto, Porto, Portugal
- Lower Genital Tract Disease Unit, Centro Hospitalar de São João, Porto, Portugal
- LAP-a Unilabs Company, Porto, Portugal
| | - Gary M Clifford
- Early Detection, Prevention, and Infections Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
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Ryu H, Narayanan N, Bhatt PJ. Prevention of infection and optimizing vaccination in the solid organ transplant candidate and recipient. Curr Opin Organ Transplant 2021; 26:445-455. [PMID: 34227584 DOI: 10.1097/mot.0000000000000902] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE OF REVIEW Infections can result in serious complications in solid organ transplant (SOT) patients. The need to remain up to date on recommendations on screening, vaccinations, and chemoprophylaxis is paramount in the management of SOT patients. The goal of this review is to provide an overview of current recommendations for the prevention of infections and optimization of vaccinations from the pretransplant through posttransplant periods. RECENT FINDINGS There is an emphasis on thorough pretransplant evaluation to guide clinicians and pretransplant testing based on epidemiological and endemic risk factors. Additionally, recent studies on vaccine safety and efficacy of newer vaccine formulations in SOT recipients are addressed. SUMMARY This review provides insight on updated recommendations for pretransplant screening, new data on vaccine optimization in SOT recipients and posttransplant prophylaxis. Further research is needed in order to improve preventive measures including screening tests, vaccines, and chemoprophylaxis.
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Affiliation(s)
- HaYoung Ryu
- Department of Pharmacy, Robert Wood Johnson University Hospital, New Brunswick
| | - Navaneeth Narayanan
- Department of Pharmacy Practice and Administration, Rutgers University Ernest Mario School of Pharmacy, Piscataway
- Division of Allergy/Immunology and Infectious Diseases, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
| | - Pinki J Bhatt
- Department of Pharmacy Practice and Administration, Rutgers University Ernest Mario School of Pharmacy, Piscataway
- Division of Allergy/Immunology and Infectious Diseases, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
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Larsen HK, Hædersdal M, Thomsen LT, Hertzum-Larsen R, Lok TT, Bonde J, Sørensen SS, Hansen JM, Palefsky JM, Kjær SK. Risk of Anal High-grade Squamous Intraepithelial Lesions Among Renal Transplant Recipients Compared With Immunocompetent Controls. Clin Infect Dis 2021; 73:21-29. [PMID: 32544223 DOI: 10.1093/cid/ciaa781] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 06/11/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Renal transplant recipients (RTRs) have increased risk of human papillomavirus (HPV)-related cancers, including anal cancer. We investigated the prevalence of anal high-grade intraepithelial lesions (HSILs) in RTRs compared with immunocompetent controls and risk factors for anal HSIL in RTRs. METHODS We included 247 RTRs and 248 controls in this cross-sectional study. We obtained anal samples for HPV testing with INNO-LiPA and performed high-resolution anoscopy on all participants. The participants completed a questionnaire on lifestyle and sexual habits. We used logistic regression to estimate odds ratios (ORs) of histologically confirmed anal HSIL in RTRs vs controls and risk factors for anal HSIL in RTRs, stratified by sex and anal high-risk (hr) HPV status, adjusting for age, smoking, lifetime sexual partners, and receptive anal sex. RESULTS RTRs had higher anal HSIL prevalence than controls, both among men (6.5% vs 0.8%; adjusted OR [aOR], 11.21 [95% confidence interval {CI}, 1.46-291.17]) and women (15.4% vs 4.0%; aOR, 6.41 [95% CI, 2.14-24.10]). Among those with anal hrHPV, RTRs had higher anal HSIL prevalence than controls (33.8% vs 9.5%; aOR, 6.06 [95% CI, 2.16-20.27]). Having had receptive anal sex (aOR, 6.23 [95% CI, 2.23-19.08]) or genital warts (aOR, 4.21 [95% CI, 1.53-11.48]) were risk factors for anal HSIL in RTRs. All HSIL cases occurred in individuals with anal hrHPV. CONCLUSIONS RTRs had increased risk of anal HSIL compared with immunocompetent controls, with particularly high prevalence in female RTRs. Receptive anal sex, previous genital warts, and anal hrHPV infection were risk factors for anal HSIL in RTRs. Screening for anal HSIL in RTRs should be considered. CLINICAL TRIALS REGISTRATION NCT03018927.
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Affiliation(s)
- Helle K Larsen
- Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.,Department of Dermatology and Venereology, Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen, Denmark
| | - Merete Hædersdal
- Department of Dermatology and Venereology, Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen, Denmark
| | - Louise T Thomsen
- Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Rasmus Hertzum-Larsen
- Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Trine Thorborg Lok
- Department of Pathology, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark
| | - Jesper Bonde
- Department of Pathology, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark
| | - Søren S Sørensen
- Department of Nephrology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Jesper Melchior Hansen
- Department of Nephrology, Copenhagen University Hospital, Herlev Hospital, Copenhagen, Denmark
| | - Joel M Palefsky
- Research and Education Center, University of California, San Francisco Anal Neoplasia Clinic, San Francisco, California, USA
| | - Susanne K Kjær
- Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.,Department of Gynecology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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Siegel R, Werner RN, Koswig S, Gaskins M, Rödel C, Aigner F. Clinical Practice Guideline: Anal Cancer—Diagnosis, Treatment and Follow-up. DEUTSCHES ARZTEBLATT INTERNATIONAL 2021; 118:217-24. [PMID: 33531112 DOI: 10.3238/arztebl.m2021.0027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND The number of anal cancer diagnoses has been rising steadily, so that the incidence has doubled in the past 20 years. Almost all anal cancers are induced by persistent infection with human papillomaviruses. Hitherto the care of patients with anal cancer has been heterogeneous and little experience exists with the primary management of anal cancer. METHODS The guideline was developed in accordance with the requirements of the German Guideline Program in Oncology. In line with the GRADE approach, the certainty of the evidence was assessed on the outcome level following a systematic literature search. Interdisciplinary working groups were set up to compile suggestions for recommendations, which were discussed and agreed upon in a formal consensus conference. RESULTS Ninety-three recommendations and statements were developed. No high-quality evidence was available to support recommendations for or against the treatment of stage I anal cancer with local excision alone as an alternative to chemoradiotherapy. Chemoradiotherapy is the gold standard in the treatment of stages II–III. Among other aspects regarding the timing and extent of response evaluation after chemoradiotherapy, the guideline panel recommended against obtaining a biopsy in the event of complete clinical response. Owing to lack of confidence in the available evidence, only open recommendations were given for treatment of stage IV. CONCLUSION This evidence-based clinical practice guideline provides a sound basis for optimizing the interdisciplinary, cross-sector care of anal cancer patients. Among other areas, gaps in research were identified with respect to the care of patients with early-stage or metastatic anal cancer. Approaches such as chemoradiotherapy combined with regional deep hyperthermia require further investigation. The role for immunotherapy in the management of metastasized anal cancer has also been insufficiently explored to date.
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P. Matylevich O, B. Shushkevich A, A. Suslova V, A. Perevoschikov P, A. Mavrichev S. Modified combined radiotherapy for cervical cancer in kidney transplant recipient. Clin Case Rep 2021; 9:2088-2093. [PMID: 33936645 PMCID: PMC8077414 DOI: 10.1002/ccr3.3950] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 01/21/2021] [Accepted: 02/07/2021] [Indexed: 12/22/2022] Open
Abstract
The management of locally advanced cervical cancer in patients with a pelvic kidney transplant is challenging because standard chemoradiotherapy may increase the risk of ureteral stenosis and obstruction or vascular damage of the graft. In the absence of clear guidelines, these patients should be treated using high-precision modern radiotherapy technique.
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Affiliation(s)
- Olga P. Matylevich
- Gynecologic Oncology DepartmentNN Alexandrov National Cancer Centre of BelarusMinskBelarus
| | | | - Valentina A. Suslova
- Radiation Oncology DepartmentNN Alexandrov National Cancer Centre of BelarusMinskBelarus
| | | | - Siarhei A. Mavrichev
- Gynecologic Oncology DepartmentNN Alexandrov National Cancer Centre of BelarusMinskBelarus
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Albuquerque A, Nathan M, Cappello C, Dinis-Ribeiro M. Anal cancer and precancerous lesions: a call for improvement. Lancet Gastroenterol Hepatol 2021; 6:327-334. [PMID: 33714370 DOI: 10.1016/s2468-1253(20)30304-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 08/29/2020] [Accepted: 09/04/2020] [Indexed: 02/07/2023]
Abstract
Anal squamous cell carcinoma is the most common type of anal cancer and is largely associated with anal human papillomavirus infection. The incidence of anal squamous cell carcinoma is increasing, and although still uncommon in the general population, a high incidence has been noted in specific population groups (eg, patients with HIV, men who have sex with men [MSM], recipients of solid organ transplants, women with genital neoplasia, and patients with systemic lupus erythematosus or inflammatory bowel disease). The higher incidence among individuals who are HIV-positive makes anal squamous cell carcinoma one of the most common non-AIDS-defining cancers among HIV-positive individuals. Anal cancer screening in high-risk groups aims to detect high-grade squamous intraepithelial lesions, which are considered anal precancerous lesions, and for which identification can provide an opportunity for prevention. A blind anal cytology is normally the first screening method, and for patients with abnormal results, this approach can be followed by an examination of the anal canal and perianal area under magnification, along with staining-a technique known as high-resolution anoscopy. Digital anorectal examination can enable early anal cancer detection. Several societies are in favour of screening for HIV-positive MSM and recipients of transplants. There are no current recommendations for screening of anal precancerous lesions via endoscopy, but in high-risk groups, a careful observation of the squamocolumnar junction should be attempted. Several treatments can be used to treat high-grade squamous intraepithelial lesions, including argon plasma coagulation or radiofrequency ablation, which are largely limited by high recurrence rates. Gastroenterologists need to be aware of anal squamous cell carcinoma and anal precancerous lesions, given that patients at high risk are frequently encountered in the gastroenterology department. We summarise simple procedures that can help in early anal squamous cell carcinoma detection.
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Affiliation(s)
- Andreia Albuquerque
- Gastroenterology Department, St James's University Hospital, Leeds, UK; CINTESIS - Center for Health Technology and Services Research, Medical Research Center, University of Porto, Porto, Portugal.
| | - Mayura Nathan
- Homerton Anogenital Neoplasia Service, Homerton University Hospital, London, UK
| | - Carmelina Cappello
- Homerton Anogenital Neoplasia Service, Homerton University Hospital, London, UK
| | - Mário Dinis-Ribeiro
- CINTESIS - Center for Health Technology and Services Research, Medical Research Center, University of Porto, Porto, Portugal; Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto, Portugal
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Imburgia TM, Shew ML, Gravitt PE, Katzenellenbogen RA. Considerations for Child Cancer Survivors and Immunocompromised Children to Prevent Secondary HPV-associated Cancers. Transplantation 2021; 105:736-742. [PMID: 32890137 DOI: 10.1097/tp.0000000000003444] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Survivors of childhood cancer and other immunocompromised children are at high risk for the development of secondary human papillomavirus (HPV)-associated cancers. In this overview, the authors examine the epidemiology of vaccine efficacy, the natural history of HPV infections, and accelerated HPV-associated cancer development in these populations. The authors highlight the opportunities for preventive care and future research directives.
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Affiliation(s)
- Teresa M Imburgia
- Division of Adolescent Medicine, Indiana University School of Medicine, Indianapolis, IN
- Epidemiology Department, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN
| | - Marcia L Shew
- Division of Adolescent Medicine, Indiana University School of Medicine, Indianapolis, IN
| | - Patti E Gravitt
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD
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Bilgi A, Gökulu ŞG, İlgen O, Kulhan M, Akgün Kavurmacı S, Toz H, Terek MC. Cervical dysplasia after renal transplantation: A retrospective cohort study. Turk J Obstet Gynecol 2021; 18:7-14. [PMID: 33715321 PMCID: PMC7962164 DOI: 10.4274/tjod.galenos.2021.28938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Objective: Since the first days of organ transplantation, it has been accepted that solid transplant recipients have a high risk of developing cancer. Chronic immunosuppression and environmental factors play a role in cancer development in recipients. In the present study, we tried to evaluate the cumulative incidence of cervical dysplasia after renal transplantation, risk factors for disease development, and the time until high-grade dysplasia occurred. Materials and Methods: A total of 50 patients with renal transplantation who presented for gynecologic follow-up was included in the study. The medical records of the patients were reviewed until the last clinical visit, their demographic characteristics, transplant history, gynecologic history, and gynecologic examination results (cervical cytology and histology reports) were reviewed. Results: Of the 50 women in the study population, 29 (58%; 95% confidence interval: 8.8-15.9) developed cervical dysplasia after the first transplant at a median follow-up of 7.8 (range: 4.6-12.9) years. Twenty-one women with benign cervical cytology before transplantation had evidence of low-grade intraepithelial lesions + after transplant (47% of these were within 2 years after transplant). During the follow-up, 8 women (18.2%) were diagnosed as having high-grade intraepithelial lesions + (within 5 years after transplantation). Conclusion: Renal transplant patients were found to have higher abnormal cervical cytology and histology rates than the normal population.
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Affiliation(s)
- Ahmet Bilgi
- Selçuk University Faculty of Medicine, Department of Gynaecology and Obstetrics, Konya, Turkey
| | - Şevki Göksun Gökulu
- Mersin University Faculty of Medicine, Department of Gynaecology and Obstetrics, Mersin, Turkey
| | - Orkun İlgen
- Dokuz Eylül University Faculty of Medicine, Department of Gynaecology and Obstetrics, İzmir, Turkey
| | - Mehmet Kulhan
- Selçuk University Faculty of Medicine, Department of Gynaecology and Obstetrics, Konya, Turkey
| | - Seda Akgün Kavurmacı
- Ege University Faculty of Medicine, Department of Gynaecology and Obstetrics, İzmir, Turkey
| | - Hüseyin Toz
- Ege University Faculty of Medicine, Department of Internal Medicine, İzmir, Turkey
| | - Mustafa Coşan Terek
- Ege University Faculty of Medicine, Department of Gynaecology and Obstetrics, İzmir, Turkey
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Khan A, Obaid T, Cetrulo L, Force L, Bhattacharya R, Greenberg RH. Anal dysplasia among solid organ transplant recipients; a cross sectional study. JOURNAL OF COLOPROCTOLOGY 2021. [DOI: 10.1016/j.jcol.2018.10.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Abstract
Introduction The incidence of anal cancer in United States has increased over of the last few decades impacting immunosuppressed populations like solid organ transplant recipients, in particular. The aim of this study was to evaluate the prevalence of anal dysplasia among solid organ transplant patients. We also attempted to identify factors that predispose solid organ transplant recipients to developing anal dysplasia.
Methods and materials Patients presenting to transplant office for routine care were recruited to participate in the study. All anal cytology specimens were collected using standard anal pap technique. The results were assessed using Bethesda classification. Information on perceived risk factors for development of anal dysplasia among our subjects was obtained.
Results Among 80 patients approached, 47 agreed to participate in the study. Of all the samples 19.1% had an inadequate amount of specimen to perform any analysis. Dysplastic cells were found in 10.5% of the specimens available for analysis. We were not able to identify any risk factors including age, gender distribution, smoking, and duration of immunosuppression that were statistically significant different between patients with anal dysplasia versus those without anal dysplasia.
Conclusions The rate of anal dysplasia detectable on cytology is high enough to warrant anal dysplasia screening in transplant recipients, which can then be followed up with high-resolution anoscopy with biopsy. Defining a cohort of patients among solid organ transplant recipients who are at an increased risk for the development of anal dysplasia mandating screening continues to be a challenge.
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Affiliation(s)
- Aimal Khan
- Einstein Healthcare Network, Department of Surgery, Philadelphia, PA, United States
| | - Thaer Obaid
- Einstein Healthcare Network, Department of Surgery, Philadelphia, PA, United States
| | - Lawrence Cetrulo
- University of Washington, Department of Surgery, Seattle, WA, United States
| | - Luanne Force
- University of Miami, Miami, Department of Surgery, FL, United States
| | - Roshmi Bhattacharya
- Einstein Healthcare Network, Department of Surgery, Philadelphia, PA, United States
| | - Richard H. Greenberg
- Einstein Healthcare Network, Department of Surgery, Philadelphia, PA, United States
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Kelgeri C, Kelly DF, Brant A, Patel M, Gupte GL. Principles of immunisation in children with solid organ transplant. Arch Dis Child 2021; 106:219-223. [PMID: 32938624 DOI: 10.1136/archdischild-2020-319822] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 08/10/2020] [Accepted: 08/10/2020] [Indexed: 12/21/2022]
Abstract
Vaccine-preventable diseases (VPD) are a significant risk to paediatric solid organ transplant (SOT) recipients on lifelong immunosuppressive therapy. Children progressing to end-stage organ dysfunction are unable to mount a robust immune response. Hence, it is important to plan vaccination early in the course of disease, especially if a child is anticipated to be a SOT candidate. Vaccine recommendations need to be individualised in this population based on vaccine history and serology. Catch-up or accelerated schedules may be used to complete vaccinations before transplant. Post-transplant, immunisation is recommenced in consultation with the transplant team taking into context the time since transplant and the intensity of the immunosuppressive regime. Inactivated vaccines are safe post-transplant but postexposure prophylaxis may still be required in children with inadequate immunity to VPD. Specific vaccines may be advised for SOT recipients travelling abroad (in consultation with a travel clinic) or those entering high-risk professions. Additionally, the vaccination status of all household members and close contacts should be reviewed and optimised, offering additional protection to the transplant recipient.
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Affiliation(s)
- Chayarani Kelgeri
- Department of Paediatric Hepatology, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
| | - Dominic F Kelly
- Department of Paediatrics, University of Oxford, Oxford, Oxfordshire, UK
| | - Alexandra Brant
- Department of Paediatric Hepatology, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
| | - Mitul Patel
- Department of Microbiology, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
| | - Girish L Gupte
- Department of Paediatric Hepatology, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
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Screening Women for Anal Cancers: Guidance for Health Care Professionals. Am J Gastroenterol 2021; 116:509-516. [PMID: 33606380 DOI: 10.14309/ajg.0000000000001186] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 01/11/2021] [Indexed: 12/11/2022]
Abstract
Anal cancer is rare in the general population but is steadily increasing in incidence over the past decade especially in women. Identification and screening of women with high risk facilitates detection of anal precancer and early-stage cancer, improves survival, and potentially uses less invasive therapies compared with the conventional chemoradiation treatments used for advanced cancers. No recently published guidelines currently describe details about screening women for anal squamous cell cancer (ASCC). The available evidence supports the existence of groups of women with higher prevalence of ASCC (e.g., women with human immunodeficiency virus, immune suppression, or previous lower-genital high-grade lesion or cancer) who would likely benefit from screening with some combination of anal cytology and human papillomavirus testing. Additional research is needed to establish the cost-effectiveness and the influence of screening on ASCC mortality rates.
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44
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Kuter BJ, Garland SM, Giuliano AR, Stanley MA. Current and future vaccine clinical research with the licensed 2-, 4-, and 9-valent VLP HPV vaccines: What's ongoing, what's needed? Prev Med 2021; 144:106321. [PMID: 33678229 DOI: 10.1016/j.ypmed.2020.106321] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 10/26/2020] [Accepted: 11/03/2020] [Indexed: 01/28/2023]
Abstract
Prophylactic HPV vaccination has been a great public health success. For >20 years, clinical trials were conducted with the 2-, 4-, and/or 9-valent vaccines in young-adult females, mid-adult women, males, and adolescents. In all studies, the vaccines were highly efficacious, immunogenic, and well tolerated. Following vaccine licensure and utilization in national vaccine programs globally (real-world settings primarily in high income countries), numerous studies demonstrated that the vaccines continue to have an excellent safety profile and have dramatically reduced the incidence of genital warts, HPV vaccine-type prevalence, and precancerous lesions. Thirty-eight clinical trials with the currently licensed HPV vaccines are ongoing. Key questions being addressed in new trials include: efficacy against persistent infection and immunogenicity of a 1-dose regimen; efficacy of 3 doses in 20-45-year-old females; use in postpartum women and immunocompromised individuals (HIV, liver and kidney transplants); dose sparing via intradermal administration; use in combination with a PD1 monoclonal antibody in patients with cervical cancer; impact on recurrent disease in women undergoing cervical conization; persistence of protection; and use to prevent oropharyngeal cancer. Additional clinical research that should be conducted includes: long-term follow-up, particularly of 1- and 2-dose regimens; further evaluation of flexible 2-dose regimens; immunogenicity of 1- or 2-dose regimens in persons ≥15 years old and immunocompromised populations; safety and immunogenicity of 1 or 2 doses in children <9 years old; assessment of the vaccine in the prevention of transmission; interchangeability with newer HPV vaccines; additional concomitant use studies; and prevention of penile cancer and recurrent respiratory papillomatosis.
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Affiliation(s)
- Barbara J Kuter
- Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
| | - Suzanne M Garland
- The University of Melbourne, The Royal Women's Hospital, and Murdoch Children's Research Institute, Parkville, Victoria, Australia
| | - Anna R Giuliano
- Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa, FL, United States of America
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Ghebre R, Berry-Lawhorn JM, D'Souza G. State of the Science: Screening, Surveillance, and Epidemiology of HPV-Related Malignancies. Am Soc Clin Oncol Educ Book 2021; 41:1-12. [PMID: 33830827 DOI: 10.1200/edbk_325319] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Oropharyngeal, cervical, vulvar, and anal cancers share a common risk factor of HPV infection. HPV vaccination is currently recommended at age 11 or 12 to prevent new HPV infections for all genders with catch-up vaccination recommened up to age 26. Despite the known effectiveness of HPV vaccination to prevent HPV-related cancer, there is continued low uptake in the United States; only 40% of eligible persons were vaccinated in 2018, though rates are 70% among teenagers. Current American Cancer Society cancer screening guidelines recommend cervical cancer screening, but do not have specific recommendations for screening for other HPV-related cancers. Oropharyngeal cancer precursors have yet to be identified, and there are currently no routine screening tests for oropharyngeal cancer recommended by the U.S. Preventive Services Task Force. The U.S. Preventive Services Task Force and American Cancer Society recommend cervical cancer screening for women at average risk up to age 65, and screening guidelines do not currently differ by HPV vaccination status. Primary HPV DNA testing was first approved for cervical cancer screening in 2016 and was shown to be superior for cervical cancer prevention. Vulvar and anal cancer precursors have been identified, but optimal screening remains unclear. Examination of the anal canal and perianus is best performed by trained clinicians using high-resolution anoscopy, and effectiveness of using high-resolution anoscopy to detect and treat anal high-grade squamous intraepithelial lesions to prevent cancer is actively being researched. Current multistep approaches to control HPV-related malignancies include HPV vaccination coupled with cervical cancer screening or surveillance for oropharyngeal, vulvar, and anal cancers.
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Affiliation(s)
- Rahel Ghebre
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN.,Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic Oncology, University of Minnesota, Minneapolis, MN
| | - J Michael Berry-Lawhorn
- Department of Medicine, Division of Hematology Oncology, Anal Neoplasia Clinic, Research, and Education Center, University of California San Francisco, San Francisco, CA
| | - Gypsyamber D'Souza
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
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Ardura MI, Coscia LA, Meyers MR. Promoting safe sexual practices and sexual health maintenance in pediatric and young adult solid organ transplant recipients. Pediatr Transplant 2021; 25:e13949. [PMID: 33491268 DOI: 10.1111/petr.13949] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 12/01/2020] [Accepted: 12/02/2020] [Indexed: 12/17/2022]
Abstract
The majority of Americans make their sexual debut during their adolescent years. Preventing pregnancy and STI during this period is vital to ensuring health and safety. As survival has improved after pediatric SOT, chronically immunosuppressed adolescents seek guidance in their medical home on matters of sexual health. Transplant practitioners often do not feel equipped to fully address these needs. This review serves as an introductory sexual preventive care resource for adolescent and young adult (AYA) SOT recipients. First, we review data on safety, efficacy, and use of contraceptive options currently available for transplant recipients with child-bearing potential. Then, we suggest a personalized sexual health discussion focusing on the diagnosis and prevention of STIs in adolescent and young adult transplant recipients. Finally, we present recommendations for STI screening of asymptomatic patients, use of index of suspicion and diagnostic testing in symptomatic patients, and opportunities to optimize STI prevention strategies. Data compiled from studies of adult SOT recipients, general population studies, and published guidelines are often extrapolated for use, as limited data exist in AYA SOT recipients. This informational dearth underscores the need for future research to better characterize the unique needs of AYA SOT recipients.
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Affiliation(s)
- Monica I Ardura
- Pediatric Infectious Diseases & Host Defense, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA
| | - Lisa A Coscia
- Transplant Pregnancy Registry International, Philadelphia, PA, USA
| | - Melissa R Meyers
- Pediatric Nephrology, Children's National Health System, Washington, DC, USA
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Robinson CH, Coughlin CC, Chanchlani R, Dharnidharka VR. Post-transplant malignancies in pediatric organ transplant recipients. Pediatr Transplant 2021; 25:e13884. [PMID: 33111463 DOI: 10.1111/petr.13884] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 09/13/2020] [Accepted: 09/24/2020] [Indexed: 12/11/2022]
Abstract
The majority of cancer diagnoses in pediatric solid organ transplant recipients (SOTRs) are post-transplantation lymphoproliferative disorders (PTLD) or skin cancers. However, pediatric SOTRs are also at significantly elevated risk for multiple other solid and hematological cancers. The risks of specific cancers vary by transplanted organ, underlying disease, and immunosuppression factors. More than one-quarter of pediatric SOTRs develop cancer within 30 years of transplantation and their risk of solid cancer is 14 times greater than the general population. Pediatric SOTRs are at significantly higher risk of cancer-associated death. Improving patient survival among pediatric SOTRs puts them at risk of adult epithelial cancers associated with environmental carcinogenic exposures. Vaccination against oncogenic viruses and avoidance of excessive immunosuppression may reduce the risk of solid cancers following transplantation. Patient and family education regarding photoprotection is an essential component of skin cancer prevention. There is significant variability in cancer screening recommendations for SOTRs and general population approaches are typically not validated for transplant populations. An individualized approach to cancer screening should be developed based on estimated cancer risk, patient life expectancy, and screening test performance.
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Affiliation(s)
- Cal H Robinson
- Department of Pediatrics, McMaster University, Hamilton, ON, Canada
| | - Carrie C Coughlin
- Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Rahul Chanchlani
- Division of Pediatric Nephrology, Department of Pediatrics, McMaster University, Hamilton, ON, Canada.,Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.,ICES McMaster, Hamilton, ON, Canada
| | - Vikas R Dharnidharka
- Division of Pediatric Nephrology, Hypertension and Pheresis, Washington University School of Medicine, Saint Louis, MO, USA
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48
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D’Arcy ME, Castenson D, Lynch CF, Kahn AR, Morton LM, Shiels MS, Pfeiffer RM, Engels EA. Risk of Rare Cancers Among Solid Organ Transplant Recipients. J Natl Cancer Inst 2021; 113:199-207. [PMID: 32462187 PMCID: PMC7850530 DOI: 10.1093/jnci/djaa078] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 05/04/2020] [Accepted: 05/21/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Immunosuppressed solid organ transplant recipients (SOTRs) have elevated rates of certain rare cancers caused by viruses. Evaluating risk of rare cancers among SOTRs may provide etiological clues for additional cancers linked to poor immunity and viral infections. METHODS We performed a cohort study of 262 455 SOTRs (1987-2014) from the US SOTR registry linked to 17 population-based cancer registries. First cancers in SOTRs were categorized using an established classification scheme based on site and histology. Standardized incidence ratios (SIRs) compared risk in SOTRs with the general population. We used Poisson regression to calculate incidence rate ratios according to immune-related SOTR characteristics, including time since transplant (ie, duration of immunosuppression). All statistical tests were 2-sided. RESULTS We examined 694 distinct cancer subtypes, with 33 manifesting statistically significantly elevated SIRs (Bonferroni P < 7.2 × 10-5). All 33 are rare (incidence <6 per 100 000 person-years) and several have known viral etiology (eg, Merkel cell carcinoma: SIR = 24.7, 95% confidence interval [CI] = 20.8 to 29.1). Additional cancers that were increased include squamous cell carcinomas of the lip (SIR range = 18.3-19.8), eye and adnexa (SIR = 13.8, 95% CI = 7.9 to 22.3), salivary gland (SIR = 9.3, 95% CI = 6.1 to 13.5), and nasal cavity and sinuses (SIR = 4.5, 95% CI = 2.8 to 6.8); sebaceous adenocarcinoma (SIR = 34.3, 95% CI = 26.3 to 44.0); malignant fibrous histiocytoma (15.4); and subtypes of bladder, kidney, lung, and colon cancer (SIR range = 3.2-13.3). Incidence of several cancers increased over time since transplant (Ptrend < .05), including squamous cell carcinomas of the lip, salivary gland, and anogenital sites. CONCLUSIONS SOTRs experience elevated rates of several rare cancers. Because some of these cancers exhibit aggressive behavior with poor outcomes, it is important to further characterize the role of immunity and the potential involvement of oncogenic viruses to improve prevention and treatment.
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MESH Headings
- Adolescent
- Adult
- Aged
- Carcinoma, Merkel Cell/epidemiology
- Carcinoma, Merkel Cell/etiology
- Carcinoma, Merkel Cell/pathology
- Carcinoma, Squamous Cell/epidemiology
- Carcinoma, Squamous Cell/etiology
- Carcinoma, Squamous Cell/immunology
- Carcinoma, Squamous Cell/pathology
- Female
- Humans
- Immune Tolerance/immunology
- Immunocompromised Host/immunology
- Immunosuppression Therapy/adverse effects
- Male
- Middle Aged
- Neoplasms/epidemiology
- Neoplasms/etiology
- Neoplasms/immunology
- Neoplasms/pathology
- Organ Transplantation/adverse effects
- Rare Diseases/epidemiology
- Rare Diseases/etiology
- Rare Diseases/immunology
- Rare Diseases/pathology
- Registries
- Risk Factors
- Sarcoma, Kaposi/epidemiology
- Sarcoma, Kaposi/etiology
- Sarcoma, Kaposi/immunology
- Sarcoma, Kaposi/pathology
- Skin Neoplasms
- Transplant Recipients
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Affiliation(s)
- Monica E D’Arcy
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | | | - Charles F Lynch
- Department of Epidemiology, University of Iowa, Iowa City, IA, USA
| | - Amy R Kahn
- Bureau of Cancer Epidemiology, New York State Department of Health, Albany, NY, USA
| | - Lindsay M Morton
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Meredith S Shiels
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Ruth M Pfeiffer
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Eric A Engels
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
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49
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Evidence of BK Polyomavirus Infection in Urothelial but not Renal Tumors from a Single Center Cohort of Kidney Transplant Recipients. Viruses 2021; 13:v13010056. [PMID: 33401589 PMCID: PMC7823775 DOI: 10.3390/v13010056] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 12/22/2020] [Accepted: 12/30/2020] [Indexed: 12/21/2022] Open
Abstract
Emerging evidence indicates that reactivation of BK polyomavirus (BKPyV) in the kidney and urothelial tract of kidney transplant recipients (KTRs) may be associated with cancer in these sites. In this retrospective study of a single center cohort of KTRs (n = 1307), 10 clear cell renal cell carcinomas and 5 urinary bladder carcinomas were analyzed from 15 KTRs for the presence of BKPyV infection through immunohistochemistry and fluorescent in situ hybridization (FISH). Three of these patients had already exhibited biopsy-proven polyomavirus-associated nephropathies (PyVAN). Although the presence of BKPyV large-T antigen was evident in the urothelium from a kidney removed soon after PyVAN diagnosis, it was undetectable in all the formalin-fixed and paraffin-embedded (FFPE) blocks obtained from the 10 kidney tumors. By contrast, large-T antigen (LT) labeling of tumor cells was detected in two out of five bladder carcinomas. Lastly, the proportion of BKPyV DNA-FISH-positive bladder carcinoma nuclei was much lower than that of LT-positive cells. Taken together, our findings further strengthen the association between BKPyV reactivation and cancer development in KTRs, especially bladder carcinoma.
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50
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Corral JE, Croome KP, Keaveny AP, Brahmbhatt B, Kröner PT, Wijarnpreecha K, Goswami RM, Raimondo M, Wallace MB, Bi Y, Mousa OY. A 3-Decade Analysis of Pancreatic Adenocarcinoma After Solid Organ Transplant. Pancreas 2021; 50:54-63. [PMID: 33370023 DOI: 10.1097/mpa.0000000000001722] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Solid organ transplant (SOT) recipients have moderately increased risk of pancreatic adenocarcinoma (PAC). We evaluated the incidence and survival of PAC in 2 cohorts and aimed to identify potential risk factors. METHODS This study performed a retrospective cohort analysis. Cohort A was extracted from the United Network of Organ Sharing data set and cohort B from SOT recipients evaluated at 3 Mayo Clinic transplant centers. The primary outcome was age-adjusted annual incidence of PAC. Descriptive statistics, hazard ratios, and survival rates were compared. RESULTS Cohort A and cohort B included 617,042 and 29,472 SOT recipients, respectively. In cohort A, the annual incidence rate was 12.78 per 100,000 in kidney-pancreas, 13.34 in liver, and 21.87 in heart-lung transplant recipients. Receiving heart-lung transplant, 50 years or older, and history of cancer (in either recipient or donor) were independent factors associated with PAC. Fifty-two patients developed PAC in cohort B. Despite earlier diagnosis (21.15% with stage I-II), survival rates were similar to those reported for sporadic (non-SOT) patients. CONCLUSIONS We report demographic and clinical risk factors for PAC after SOT, many of which were present before transplant and are common to sporadic pancreatic cancer. Despite the diagnosis at earlier stages, PAC in SOT portends a very poor survival.
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Affiliation(s)
- Juan E Corral
- From the Division of Gastroenterology and Hepatology
| | | | | | | | - Paul T Kröner
- From the Division of Gastroenterology and Hepatology
| | | | - Rohan M Goswami
- Department of Transplantation, Mayo Clinic, Jacksonville, FL
| | | | | | - Yan Bi
- From the Division of Gastroenterology and Hepatology
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