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Kumari S, Mishra S, Ali W, Singh US, Shabbir N, Kumar V, Akhtar N, Hadi R. Implication of circulating miRNAs as potential diagnostic biomarker in oropharyngeal squamous cell Carcinoma: Association with Human Papilloma Virus. Oral Oncol 2025; 165:107305. [PMID: 40286701 DOI: 10.1016/j.oraloncology.2025.107305] [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: 10/08/2024] [Revised: 02/10/2025] [Accepted: 04/13/2025] [Indexed: 04/29/2025]
Abstract
BACKGROUND Over the past decades, significant progress has been made in the early diagnosis and treatment of oropharyngeal squamous cell carcinoma (OPSCC). However, the survival rate has not improved. Human papillomavirus (HPV) is a major risk factor for the development of oropharyngeal cancer. Therefore, understanding the molecular mechanisms underlying OPSCC may help define improved diagnostic and prognostic strategies. Previous studies on tissue samples have linked microRNAs (miRNAs) to the progression of OPSCC. This study aimed to develop a panel of diagnostic biomarkers based on the serum miRNA signature in OPSCC that correlates with HPV status. MATERIALS AND METHODS Paired serum and tissue samples were collected from 30 OPSCC patients and 20 healthy controls. Based on previous studies on OPSCC tissue samples, a set of six miRNAs (miR-93, miR-222, miR-199, miR-320, miR-145, and miR-126) was selected due to their association with OPSCC development and progression. RT-qPCR was used to compare miRNA expression in paired samples, with miR-16 serving as the reference gene for normalization. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic potential of these serum miRNAs. RESULTS The mean relative fold change for serum miR-93 and miR-222 was upregulated, whereas miR-199, miR-320, miR-145, and miR-126 were downregulated in OPSCC compared to normal controls. A similar trend of upregulation and downregulation was observed in tissue samples. The mean relative expression of miR-93 was significantly associated with HPV status (p < 0.0001). Additionally, the mean relative expression levels of all six miRNAs (miR-93, miR-222, miR-199, miR-320, miR-145, and miR-126) were significantly different between the serum of normal controls and early-stage OPSCC patients. The serum miRNA panel, including miR-93, miR-222, miR-199, miR-320, miR-145, and miR-126, demonstrated significant diagnostic potential in distinguishing OPSCC from normal controls. CONCLUSION Our findings suggest that a panel of OPSCC-related miRNAs demonstrates concordant expression levels in serum and tissue of OPSCC, and may serve as a minimally invasive diagnostic biomarker for OPSCC. Further studies with a larger sample size are needed to confirm these findings, particularly in HPV-associated OPSCC.
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Affiliation(s)
- Swati Kumari
- Department of Pathology, King George Medical University, Lucknow 226003, India
| | - Sridhar Mishra
- Department of Plastic & Reconstructive Surgery, King George Medical University, Lucknow 226003, India
| | - Wahid Ali
- Department of Pathology, King George Medical University, Lucknow 226003, India.
| | - Uma Shankar Singh
- Department of Pathology, King George Medical University, Lucknow 226003, India
| | - Nida Shabbir
- Department of Pathology, King George Medical University, Lucknow 226003, India
| | - Vijay Kumar
- Department of Surgical Oncology, King George Medical University, Lucknow 226003, India
| | - Naseem Akhtar
- Department of Surgical Oncology, King George Medical University, Lucknow 226003, India
| | - Rahat Hadi
- Department of Radiation Oncology, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow 226010 Uttar Pradesh, India
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Nam HJ, Ryu H, Lee DW, Byeon JY, Kim JH, Lee JH, Lim S, Choi HJ. Expression rates of p16, p53 in head and neck cutaneous squamous cell carcinoma based on human-papillomavirus positivity. World J Clin Cases 2025; 13:99463. [PMID: 40144480 PMCID: PMC11670024 DOI: 10.12998/wjcc.v13.i9.99463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 11/02/2024] [Accepted: 12/02/2024] [Indexed: 12/12/2024] Open
Abstract
BACKGROUND The high prevalence of human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (SCC) is well established, and p16 expression is a strong predictor. HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins. However, research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC (HNCSCC), particularly in Asian populations, remains limited. This retrospective study surveyed 62 patients with HNSCC (2011-2020), excluding those with facial warts or other skin cancer. AIM To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations. METHODS All patients underwent wide excision and biopsy. Immunohistochemical staining for HPV, p16, and p53 yielded positive and negative results. The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency. RESULTS Of the 62 patients, 20 (32.26%) were male, with an average age of 82.27 years (range 26-103 years). High-risk included 19 cases (30.65%), with the eyelid and lip being the most common sites (five cases, 8.06%). Middle-risk included 43 cases (69.35%), with the cheek being the most common (29 cases, 46.77%). The p16 expression was detected in 24 patients (38.71%), p53 expression in 42 patients (72.58%), and HPV in five patients (8.06%). No significant association was found between p16 expression and the presence of HPV (P > 0.99), with a positive predictive value of 8.33%. CONCLUSION This study revealed that p16, a surrogate HPV marker in oropharyngeal SCC, is not reliable in HNCSCC, providing valuable insights for further research in Asian populations.
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Affiliation(s)
- Ha-Jong Nam
- Department of Plastic and Reconstructive Surgery, Soonchunhyang University Gumi Hospital, Gumi-si 39371, South Korea
| | - Heongrae Ryu
- Department of Plastic and Reconstructive Surgery, College of Medicine, Soonchunhyang University, Cheonan-si 31151, South Korea
| | - Da-Woon Lee
- Department of Plastic and Reconstructive Surgery, College of Medicine, Soonchunhyang University, Cheonan-si 31151, South Korea
| | - Je Yeon Byeon
- Department of Plastic and Reconstructive Surgery, College of Medicine, Soonchunhyang University, Cheonan-si 31151, South Korea
| | - Jun Hyuk Kim
- Department of Plastic and Reconstructive Surgery, College of Medicine, Soonchunhyang University, Cheonan-si 31151, South Korea
| | - Ji Hye Lee
- Department of Pathology, Soonchunhyang University Hospital, Cheonan-si 31151, South Korea
| | - Soomin Lim
- Bachelor of Medicine and Bachelor of Surgery, University College London, Medical School, London WC1E 6DE, United Kingdom
| | - Hwan Jun Choi
- Department of Plastic and Reconstructive Surgery, College of Medicine, Soonchunhyang University, Cheonan-si 31151, South Korea
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Zhao BY, Hirayama S, Goss D, Zhao Y, Faden DL. Human papillomavirus-associated nasopharyngeal carcinoma: A systematic review and meta-analysis. Oral Oncol 2024; 159:107057. [PMID: 39383626 DOI: 10.1016/j.oraloncology.2024.107057] [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: 09/06/2024] [Accepted: 09/25/2024] [Indexed: 10/11/2024]
Abstract
OBJECTIVE Human papillomavirus (HPV) is known to affect head and neck sites beyond the oropharynx, including the nasopharynx. Unlike HPV-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC), HPV-associated nasopharyngeal carcinoma (HPV+NPC) is not well characterized and the true prevalence in non-endemic regions is poorly described. Here, we sought to obtain a global point prevalence of HPV in NPC, stratified by geographic region. DATA SOURCES EMBASE, OVID Medline, and Web of Science were systematically searched for available evidence on September 21, 2022 for articles published between January 1, 1990 and September 21, 2022. REVIEW METHODS We reviewed the literature for all studies examining NPC and HPV status in adult patients that provided a quantitative HPV prevalence. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Main outcome and measures included HPV+NPC prevalence estimates stratified by geographic region, along with other clinical and demographic features. RESULTS Of the 1567 citations retrieved, 46 studies encompassing 6314 NPC patients were eligible for statistical analysis. The global prevalence of HPV+NPC was 0.18 (95% CI 0.14-0.23). When stratified by geographic region, prevalence was highest in North America (0.25, 95% CI 0.17-0.36), which is a non-endemic region for NPC and also has highest prevalence for HPV+OPSCC. Asia, an endemic area, had the lowest HPV prevalence estimate (0.13, 95% CI 0.08-0.22). HPV 16 (44%) and 18 (33%) were the predominant genotypes in HPV+NPC, dissimilar to HPV+OPSCC. CONCLUSION This systematic review and meta-analysis provides a global point prevalence of HPV+NPC stratified by geographic region and suggests that HPV is a significant etiological factor of NPC in North America.
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Affiliation(s)
- Brian Y Zhao
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, USA
| | - Shun Hirayama
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, USA
| | - Deborah Goss
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, USA
| | - Yan Zhao
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, USA
| | - Daniel L Faden
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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Zhao BY, Hirayama S, Goss D, Zhao Y, Faden DL. Human Papillomavirus-Associated Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.09.10.24313140. [PMID: 39314950 PMCID: PMC11419204 DOI: 10.1101/2024.09.10.24313140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 09/25/2024]
Abstract
Objective Human papillomavirus (HPV) is known to affect head and neck sites beyond the oropharynx, including the nasopharynx. Unlike HPV-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC), HPV-associated nasopharyngeal carcinoma (HPV+NPC) is not well characterized and the true prevalence in non-endemic regions is poorly described. Here, we sought to obtain a global point prevalence of HPV in NPC, stratified by geographic region. Data Sources EMBASE, OVID Medline, and Web of Science were systematically searched for available evidence on September 21, 2022 for articles published between January 1, 1990 and September 21, 2022. Review Methods We reviewed the literature for all studies examining NPC and HPV status in adult patients that provided a quantitative HPV prevalence. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Main outcome and measures included HPV+NPC prevalence estimates stratified by geographic region, along with other clinical and demographic features. Results Of the 1567 citations retrieved, 46 studies encompassing 6314 NPC patients were eligible for statistical analysis. The global prevalence of HPV+NPC was 0.18 (95% CI 0.14-0.23). When stratified by geographic region, prevalence was highest in North America (0.25, 95% CI 0.17-0.36), which is a non-endemic region for NPC and also has highest prevalence for HPV+OPSCC. Asia, an endemic area, had the lowest HPV prevalence estimate (0.13, 95% CI 0.08-0.22). HPV 16 (44%) and 18 (33%) were the predominant genotypes in HPV+NPC, dissimilar to HPV+OPSCC. Conclusion This systematic review and meta-analysis provides a global point prevalence of HPV+NPC stratified by geographic region and suggests that HPV is a significant etiological factor of NPC in North America.
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Affiliation(s)
- Brian Y. Zhao
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts
| | - Shun Hirayama
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts
| | - Deborah Goss
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts
| | - Yan Zhao
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts
| | - Daniel L. Faden
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts
- Harvard Medical School, Boston, Massachusetts
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts
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Lulić L, Šimić I, Božinović K, Pešut E, Manojlović L, Grce M, Dediol E, Sabol I, Tomaić V. Moderate SCRIB Expression Levels Correlate with Worse Prognosis in OPSCC Patients Regardless of HPV Status. Cells 2024; 13:1002. [PMID: 38920638 PMCID: PMC11201649 DOI: 10.3390/cells13121002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 05/29/2024] [Accepted: 06/04/2024] [Indexed: 06/27/2024] Open
Abstract
Head and neck cancers rank as the sixth most prevalent cancers globally. In addition to traditional risk factors such as smoking and alcohol use, human papillomavirus (HPV) infections are becoming a significant causative agent of head and neck cancers, particularly among Western populations. Although HPV offers a significant survival benefit, the search for better biomarkers is still ongoing. In the current study, our objective was to investigate whether the expression levels of three PDZ-domain-containing proteins (SCRIB, NHERF2, and DLG1), known HPV E6 cellular substrates, influence the survival of HNSCC patients treated by primary surgery (n = 48). Samples were derived from oropharyngeal and oral cancers, and HPV presence was confirmed by PCR and p16 staining. Clinical and follow-up information was obtained from the hospital database and the Croatian Cancer registry up to November 2023. Survival was evaluated using the Kaplan-Meier method and Cox proportional hazard regression. The results were corroborated through the reanalysis of a comparable subset of TCGA cancer patients (n = 391). In conclusion, of the three targets studied, only SCRIB levels were found to be an independent predictor of survival in the Cox regression analysis, along with tumor stage. Further studies in a more typical Western population setting are needed since smoking and alcohol consumption are still prominent in the Croatian population, while the strongest association between survival and SCRIB levels was seen in HPV-negative cases.
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Affiliation(s)
- Lucija Lulić
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
- Division of Molecular Biology, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
| | - Ivana Šimić
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
| | - Ksenija Božinović
- Division of Molecular Biology, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
| | - Ena Pešut
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
| | - Luka Manojlović
- Department of Pathology and Cytology, University Hospital Dubrava, 10000 Zagreb, Croatia
| | - Magdalena Grce
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
| | - Emil Dediol
- Department of Maxillofacial Surgery, University Hospital Dubrava, 10000 Zagreb, Croatia
| | - Ivan Sabol
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
| | - Vjekoslav Tomaić
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
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Harbor SN, Schneider JW, Solomons N, Sanderson M, Afrogheh AH. An Evaluation of High-Risk HPV in Squamous Cell Carcinomas of the Lip in a South African Cohort. Head Neck Pathol 2024; 18:36. [PMID: 38709462 PMCID: PMC11074087 DOI: 10.1007/s12105-024-01639-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 03/18/2024] [Indexed: 05/07/2024]
Abstract
BACKGROUND To determine the prevalence of HR-HPV in a series of lip SCC from South African patients, using currently accepted HPV-testing methodologies and to define the clinical and histomorphologic features of HPV-associated lip SCC. METHODS Fifty SCC of lip and 50 control cases were tested for HR-HPV using p16 and HR-HPV DNA PCR. p16-equivocal/positive and HPV DNA PCR-positive SCC were further evaluated for the expression of HPV-16 and HPV-18 mRNA transcripts using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to confirm transcriptionally active HPV. RESULTS p16 was positive in 22% (n = 11) and equivocal in 4% (n = 2) of the SCC. One p16-positive case showed positivity for both HPV-16 DNA and HPV-16 E6/E7 mRNA transcripts (HPV prevalence rate of 2%). The HPV-positive case was non-keratinizing and occurred in an 80-year-old female. The two p16-equivocal cases were HR-HPV DNA positive and mRNA PCR negative. p16 was found to have a positive predictive value of 9%. CONCLUSION Findings from our cohort of lip SCC suggest that HR-HPV may have an insignificant role in the pathogenesis of SCC at this site. Due to its low ppv, p16 is insufficient to establish HR-HPV infection in SCC of the lip. The combination of p16 and DNA PCR appears to correlate with the presence of transcriptionally active virus. HPV E6/E7 mRNA detection is the gold standard for identifying HR-HPV. mRNA testing is not widely available in sub-Saharan Africa due to technical and financial constraints; however, the test appears to be of great value in p16-equivocal lip SCC.
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Affiliation(s)
- Sharon N Harbor
- Division of Anatomical Pathology, Stellenbosch University, Cape Town, South Africa
- National Health Laboratory Service, Tygerberg Hospital, Cape Town, South Africa
| | - Johann W Schneider
- Division of Anatomical Pathology, Stellenbosch University, Cape Town, South Africa
- National Health Laboratory Service, Tygerberg Hospital, Cape Town, South Africa
| | - Nadine Solomons
- Division of Anatomical Pathology, Stellenbosch University, Cape Town, South Africa
| | - Micheline Sanderson
- Division of Anatomical Pathology, Stellenbosch University, Cape Town, South Africa
| | - Amir H Afrogheh
- Division of Anatomical Pathology, Stellenbosch University, Cape Town, South Africa.
- Department of Oral and Maxillofacial Pathology, National Health Laboratory Service, University of the Western Cape, Cape Town, South Africa.
- National Health Laboratory Service, Tygerberg Hospital, Cape Town, South Africa.
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Saulters EL, Kennedy PT, Carter RJ, Alsufyani A, Jones TM, Woolley JF, Dahal LN. Differential Regulation of the STING Pathway in Human Papillomavirus-Positive and -Negative Head and Neck Cancers. CANCER RESEARCH COMMUNICATIONS 2024; 4:118-133. [PMID: 38147007 PMCID: PMC10793589 DOI: 10.1158/2767-9764.crc-23-0299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 10/19/2023] [Accepted: 12/19/2023] [Indexed: 12/27/2023]
Abstract
Squamous cell carcinomas, which arise from the cells that line the mucosal surfaces of the head and neck, represent the most common type of head and neck cancers (HNSCC). Human papillomavirus (HPV) infection has been strongly associated with the development of oropharyngeal cancers, which are cancers that occur in the back of the throat, including the tonsils and base of the tongue. HNSCCs with and without HPV infection have distinct pathology, with HPV-positive patients having higher levels of immune infiltration, activation in the tumor microenvironment and better response to radiation and chemotherapy. It is, however, unclear whether HPV infection in HNSCCs has the potential to activate innate-immune sensing pathways and if these cancers possess intrinsic immunogenicity associated with HPV infection. Here we investigate the innate immune stimulator of interferon genes (STING) pathway and immune responses to STING activation in HNSCCs and uncover fundamental differences in the regulation of this pathway in cell lines versus primary human clinical specimens. We show that while STING is differentially expressed in HPV-positive and -negative HNSCC cell lines, they exhibit a gross functional defect in signaling through this pathway. However, STING activation in immune cell populations generated immune signatures predicted to elicit useful tumoricidal mechanisms. In contrast, IHC analysis of human tissue microarrays revealed enhanced STING expression in HPV-related tumors and high intratumoral expression of STING correlated with increased survival. SIGNIFICANCE STING is an important innate immune sensor of cytosolic DNA, inducing essential antiviral and antitumoral responses. This research shows that STING expression is enhanced in HPV-positive HNSCC patient tissue, with high intratumoral STING expression correlating with increased survival. In addition, STING activation in immune cell populations augmented antitumoral effects against HNSCCs, suggesting patients may benefit from the use of STING agonists in combination with traditional therapies.
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Affiliation(s)
- Emma L. Saulters
- Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom
| | - Paul T. Kennedy
- Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom
| | - Rachel J. Carter
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom
| | - Abdullah Alsufyani
- Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom
| | - Terence M. Jones
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom
| | - John F. Woolley
- Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom
| | - Lekh N. Dahal
- Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom
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Awawda M, Salman S, Billan S. The Clinical Characteristics and Outcomes of Human Papillomavirus-Positive Nasopharyngeal Carcinoma in a Single-Institution Cohort. J Clin Med 2023; 12:4264. [PMID: 37445299 DOI: 10.3390/jcm12134264] [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: 05/22/2023] [Revised: 06/12/2023] [Accepted: 06/23/2023] [Indexed: 07/15/2023] Open
Abstract
BACKGROUND Nasopharyngeal carcinoma (NPC) is a head and neck cancer more frequent among East Asian populations compared with Western populations. While much is known about human papillomavirus's (HPV's) role in oropharyngeal cancer (OPC), little is known about its prevalence and prognostic value in NPC. The aim of this study is to investigate the role of HPV in NPC treated with definitive radiotherapy at a single institution. METHODS A retrospective cohort analysis of patient's medical records and HPV status treated for NPC in Rambam Health Care Campus (Rambam HCC). Immunohistochemical staining for p16 was used as a surrogate marker of HPV infection in the tumor cells. All specimens were stained and evaluated by pathologists at the referring center independently. RESULTS In total, 87 patients diagnosed with NPC were treated at Rambam HCC between 2005 and 2018. Seventy-four patients had accessible data on the disease's clinical parameters and p16 status. In total, 10/74 (13.5%) had p16-positive staining in tumor cells; 75% were men and over 50% were smokers. The average age of diagnosis for the whole cohort was 48 years, being lower for p16-positive patients compared with p16-negative patients at 43 and 49 years old, respectively. A total of 84% of the patients had advanced disease of stage III and IV at presentation. Only 16% were diagnosed with stage I and II. Unlike the p16-negative group, the p16-positive group did not include any stage I or II disease. In univariate and multivariate analysis of overall survival rates, the age at diagnosis and the nodal spread status were the only statistically significant measures. P16 status was not found to be associated with survival. CONCLUSIONS The HPV prevalence in NPC is nontrivial. p16-positive patients had significantly less nodal spread and tended to be younger. Both age and nodal status were significantly correlated with the survival, but P16 status was not prognostic. Further large-scale trials are needed to elucidate the role of HPV in NPC.
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Affiliation(s)
- Muhammad Awawda
- Joseph Fishman Oncology Center, Rambam Health Care Campus, Haifa 3109601, Israel
| | - Saeed Salman
- Joseph Fishman Oncology Center, Rambam Health Care Campus, Haifa 3109601, Israel
| | - Salem Billan
- Joseph Fishman Oncology Center, Rambam Health Care Campus, Haifa 3109601, Israel
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Restaino AC, Walz A, Vermeer SJ, Barr J, Kovács A, Fettig RR, Vermeer DW, Reavis H, Williamson CS, Lucido CT, Eichwald T, Omran DK, Jung E, Schwartz LE, Bell M, Muirhead DM, Hooper JE, Spanos WC, Drapkin R, Talbot S, Vermeer PD. Functional neuronal circuits promote disease progression in cancer. SCIENCE ADVANCES 2023; 9:eade4443. [PMID: 37163587 PMCID: PMC10171812 DOI: 10.1126/sciadv.ade4443] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 04/04/2023] [Indexed: 05/12/2023]
Abstract
The molecular and functional contributions of intratumoral nerves to disease remain largely unknown. We localized synaptic markers within tumors suggesting that these nerves form functional connections. Consistent with this, electrophysiological analysis shows that malignancies harbor significantly higher electrical activity than benign disease or normal tissues. We also demonstrate pharmacologic silencing of tumoral electrical activity. Tumors implanted in transgenic animals lacking nociceptor neurons show reduced electrical activity. These data suggest that intratumoral nerves remain functional at the tumor bed. Immunohistochemical staining demonstrates the presence of the neuropeptide, Substance P (SP), within the tumor space. We show that tumor cells express the SP receptor, NK1R, and that ligand/receptor engagement promotes cellular proliferation and migration. Our findings identify a mechanism whereby intratumoral nerves promote cancer progression.
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Affiliation(s)
- Anthony C. Restaino
- Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA
- University of South Dakota Sanford School of Medicine, Vermillion, SD, USA
| | - Austin Walz
- Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA
| | | | - Jeffrey Barr
- Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA
| | - Attila Kovács
- Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA
| | - Robin R. Fettig
- Basic Biomedical Sciences Program, University of South Dakota, Vermillion, SD, USA
| | - Daniel W. Vermeer
- Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA
| | - Hunter Reavis
- Penn Ovarian Cancer Research Center, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | | | | | - Tuany Eichwald
- Karolinska Institutet, Department of Pharmacology and Physiology, Solna, Sweden
- Queen’s University, Department of Biomedical and Molecular Sciences, Kingston, Ontario, Canada
| | - Dalia K. Omran
- Penn Ovarian Cancer Research Center, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Euihye Jung
- Penn Ovarian Cancer Research Center, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Lauren E. Schwartz
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Maria Bell
- Sanford Gynecologic Oncology, Sanford Health, Sioux Falls, SD, USA
| | | | - Jody E. Hooper
- Legacy Gift Rapid Autopsy Program, Johns Hopkins University, Baltimore, MD, USA
| | - William C. Spanos
- Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA
- Sanford Ear, Nose and Throat Clinic, Sioux Falls, SD, USA
| | - Ronny Drapkin
- Penn Ovarian Cancer Research Center, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Sebastien Talbot
- Karolinska Institutet, Department of Pharmacology and Physiology, Solna, Sweden
- Queen’s University, Department of Biomedical and Molecular Sciences, Kingston, Ontario, Canada
| | - Paola D. Vermeer
- Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA
- University of South Dakota Sanford School of Medicine, Vermillion, SD, USA
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Šimić I, Božinović K, Milutin Gašperov N, Kordić M, Pešut E, Manojlović L, Grce M, Dediol E, Sabol I. Head and Neck Cancer Patients' Survival According to HPV Status, miRNA Profiling, and Tumour Features-A Cohort Study. Int J Mol Sci 2023; 24:ijms24043344. [PMID: 36834756 PMCID: PMC9959828 DOI: 10.3390/ijms24043344] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 02/01/2023] [Accepted: 02/02/2023] [Indexed: 02/10/2023] Open
Abstract
Head and neck cancers (HNC) are a heterogeneous group of tumours mainly associated with tobacco and alcohol use and human papillomavirus (HPV). Over 90% of all HNC are squamous cell carcinomas (HNSCC). Sample material from patients diagnosed with primary HNSCC (n = 76) treated with surgery as primary treatment at a single centre were assessed for HPV genotype, miR-9-5p, miR-21-3p, miR-29a-3p and miR-100-5p expression levels. Clinical and pathological data were collected from medical records. Patients were enrolled between 2015 and 2019 and followed-up until November 2022. Overall survival, disease-specific survival and disease-free survival were assessed and correlated with clinical, pathological, and molecular data. Kaplan-Meier and Cox proportional hazard regression was used to assess different risk factors. In the study, male gender, HPV-negative HNSCC (76.3%) mostly located in the oral region (78.9%) predominated. Most patients had stage IV cancer (47.4%), and the overall survival rate was 50%. HPV was found not to affect survival, indicating that in this population, classic risk factors predominate. The presence of both perineural and angioinvasion was strongly associated with survival in all analyses. Of all miRNAs assessed, only upregulation of miR-21 was consistently shown to be an independent predictor of poor prognosis and may thus serve as a prognostic biomarker in HNSCC.
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Affiliation(s)
- Ivana Šimić
- Laboratory for Molecular Virology and Bacteriology, Ruđer Bošković Institute, 10000 Zagreb, Croatia
| | - Ksenija Božinović
- Laboratory for Cell Biology and Signalling, Ruđer Bošković Institute, 10000 Zagreb, Croatia
| | - Nina Milutin Gašperov
- Laboratory for Molecular Virology and Bacteriology, Ruđer Bošković Institute, 10000 Zagreb, Croatia
| | - Mario Kordić
- Department of Maxillofacial Surgery, Clinical Hospital Dubrava, 10000 Zagreb, Croatia
- Department of Maxillofacial Surgery, Clinical Hospital Mostar, 88000 Mostar, Bosnia and Herzegovina
| | - Ena Pešut
- Laboratory for Molecular Virology and Bacteriology, Ruđer Bošković Institute, 10000 Zagreb, Croatia
| | - Luka Manojlović
- Clinical Department of Pathology and Cytology, Clinical Hospital Dubrava, 10000 Zagreb, Croatia
| | - Magdalena Grce
- Laboratory for Molecular Virology and Bacteriology, Ruđer Bošković Institute, 10000 Zagreb, Croatia
| | - Emil Dediol
- Department of Maxillofacial Surgery, Clinical Hospital Dubrava, 10000 Zagreb, Croatia
- Correspondence: (E.D.); (I.S.)
| | - Ivan Sabol
- Laboratory for Molecular Virology and Bacteriology, Ruđer Bošković Institute, 10000 Zagreb, Croatia
- Correspondence: (E.D.); (I.S.)
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11
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Chen X, Liu Y, Liu H, Wang ZW, Zhu X. Unraveling diverse roles of noncoding RNAs in various human papillomavirus negative cancers. Pharmacol Ther 2022; 238:108188. [PMID: 35421419 DOI: 10.1016/j.pharmthera.2022.108188] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/02/2022] [Accepted: 04/07/2022] [Indexed: 12/17/2022]
Abstract
Human papillomavirus (HPV)-negative tumors distinguish from cancers associated with HPV infection. Due to its high rate of lymph node metastasis and difficulty in inchoate discover and diagnosis, the treatment efficacy of HPV-negative cancers is unsatisfactory. Epidemiological evidence suggests that HPV-negative tumor patients have a poor prognosis, and the mortality is higher than that of cancer patients caused by HPV infection. Evidence has demonstrated that noncoding RNAs (ncRNAs) play a crucial role in regulation of physiological and developmental processes. Therefore, dysregulated ncRNAs are involved in the occurrence of diversified diseases, including cancer. In cumulative studies, ncRNAs are concerned with pathogenetic mechanisms of HPV-negative tumors via regulating gene expression and signal transduction. It is important to decipher the functions of ncRNAs in HPV-negative cancers and identify the potential biomarkers, which will bring new treatment strategies for improving outcome of cancer therapy. In this review, we demonstrated the effects of ncRNAs via regulating the development and progression of HPV- negative tumors by directly or indirectly acting on target molecules, which provide a basis for future tumor targeted therapy by targeting ncRNAs for HPV-negative cancers.
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Affiliation(s)
- Xin Chen
- Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Yi Liu
- Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Hejing Liu
- Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Zhi-Wei Wang
- Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China; Department of Research and Development, Beijing Zhongwei Research Center of Biological and Translational Medicine, Beijing 100161, China.
| | - Xueqiong Zhu
- Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China.
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12
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High Risk-Human Papillomavirus in HNSCC: Present and Future Challenges for Epigenetic Therapies. Int J Mol Sci 2022; 23:ijms23073483. [PMID: 35408843 PMCID: PMC8998945 DOI: 10.3390/ijms23073483] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 03/16/2022] [Accepted: 03/18/2022] [Indexed: 02/01/2023] Open
Abstract
Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly heterogeneous group of tumors characterized by an incidence of 650,000 new cases and 350,000 deaths per year worldwide and a male to female ratio of 3:1. The main risk factors are alcohol and tobacco consumption and Human Papillomavirus (HPV) infections. HNSCC cases are divided into two subgroups, the HPV-negative (HPV−) and the HPV-positive (HPV+) which have different clinicopathological and molecular profiles. However, patients are still treated with the same therapeutic regimens. It is thus of utmost importance to characterize the molecular mechanisms underlying these differences to find new biomarkers and novel therapeutic targets towards personalized therapies. Epigenetic alterations are a hallmark of cancer and can be exploited as both promising biomarkers and potential new targets. E6 and E7 HPV oncoviral proteins besides targeting p53 and pRb, impair the expression and the activity of several epigenetic regulators. While alterations in DNA methylation patterns have been well described in HPV+ and HPV− HNSCC, accurate histone post-translational modifications (hPTMs) characterization is still missing. Herein, we aim to provide an updated overview on the impact of HPV on the hPTMs landscape in HNSCC. Moreover, we will also discuss the sex and gender bias in HNSCC and how the epigenetic machinery could be involved in this process, and the importance of taking into account sex and/or gender also in this field.
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13
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Impact of HPV status on metastatic patterns and survival in non-oropharyngeal head and neck cancer with distant metastasis. Eur Arch Otorhinolaryngol 2022; 279:3029-3039. [DOI: 10.1007/s00405-022-07259-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Accepted: 01/04/2022] [Indexed: 12/24/2022]
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14
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Patel EJ, Oliver JR, Jacobson AS, Li Z, Hu KS, Tam M, Vaezi A, Morris LGT, Givi B. Human Papillomavirus in Patients With Hypopharyngeal Squamous Cell Carcinoma. Otolaryngol Head Neck Surg 2022; 166:109-117. [PMID: 33845656 DOI: 10.1177/01945998211004586] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 03/03/2021] [Indexed: 11/17/2022]
Abstract
OBJECTIVE Assess the testing rates and prognostic significance of human papilloma virus (HPV) status in hypopharynx malignancies. STUDY DESIGN Historical cohort study. SETTING National Cancer Database. METHODS Review of the National Cancer Database was conducted between 2010 and 2017 for squamous cell carcinomas (SCCs) of the hypopharynx. We investigated how often the tumors were tested for HPV and whether it was associated with survival outcomes. RESULTS A total of 13,269 patients with hypopharynx malignancies were identified. Most cases were not tested for HPV status (n = 8702, 65.6%). Of those tested, 872 (19.1%) were positive for HPV and 3695 (80.9%) were negative. The proportion of nonoropharyngeal SCCs tested for HPV increased nearly every year during the study, with roughly one-third of cases (31.9%) being tested in 2017. In the facilities classified as high-testing centers of nonoropharyngeal SCCs of the head and neck, 18.7% of hypopharyngeal tumors were HPV positive. HPV-negative status was associated with worse survival on multivariable analysis. In propensity score-matched analysis controlling for all factors significant in multivariable regression, 2-year survival remained higher in the HPV-positive cohort (77.7% vs 63.1%, P < .001). CONCLUSIONS HPV-positive tumors constitute a sizable minority of hypopharynx tumors and are associated with improved survival. Expansion of HPV testing to hypopharynx malignancies may be warranted.
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Affiliation(s)
- Evan J Patel
- Department of Otolaryngology-Head and Neck Surgery, NYU School of Medicine, New York, New York, USA
| | - Jamie R Oliver
- Department of Otolaryngology-Head and Neck Surgery, NYU School of Medicine, New York, New York, USA
| | - Adam S Jacobson
- Department of Otolaryngology-Head and Neck Surgery, NYU School of Medicine, New York, New York, USA
| | - Zujun Li
- Department of Medical Oncology, NYU School of Medicine, New York, New York, USA
| | - Kenneth S Hu
- Department of Radiation Oncology, NYU School of Medicine, New York, New York, USA
| | - Moses Tam
- Department of Radiation Oncology, NYU School of Medicine, New York, New York, USA
| | - Alec Vaezi
- Department of Otolaryngology-Head and Neck Surgery, NYU School of Medicine, New York, New York, USA
| | - Luc G T Morris
- Department of Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Babak Givi
- Department of Otolaryngology-Head and Neck Surgery, NYU School of Medicine, New York, New York, USA
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15
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Guo L, Fu Y, Miao C, Wu S, Zhu Y, Liu Y. Second Primary Malignancy in Patients with Hypopharyngeal Carcinoma: A SEER-Based Study. Int J Gen Med 2021; 14:8847-8861. [PMID: 34858052 PMCID: PMC8630468 DOI: 10.2147/ijgm.s339595] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 11/04/2021] [Indexed: 12/19/2022] Open
Abstract
Background A population-based analysis of the risk of secondary primary malignancy (SPM) in patients with hypopharyngeal carcinoma (HPC) has been lacking in the literature. Therefore, we conducted this study to determine the risk factors and assess the effects of SPM on the overall survival (OS) and cancer-specific survival (CSS) of patients with HPC. Methods Data on selected patients diagnosed with HPC from the Surveillance, Epidemiology and End Results (SEER) database between 1973 and 2015 were examined through logistic regression, Cox regression and nomogram methods. Results The overall risk of SPM in patients with HPC was higher than that in the general population (SIR: 2.77; P < 0.05). The specific-site, including the oral cavity, pharynx, digestive system, respiratory system and endocrine system, had a relatively higher risk of SPM. The overall risks of the subgroup of people 55–75 years of age and all subgroups of sex, race and latency were significantly elevated. In addition, patients with HPC were more likely to have been diagnosed in 2010–2015 (vs 2004–2009; P = 0.002), to be unmarried (vs married; P = 0.008), to have distant metastasis (vs no metastasis; P = 0.016) and to have had no surgery for the first tumor (vs surgery for the first tumor; P = 0.021), and these aspects were associated with a significantly elevated risk of developing SPM. SPM was independently associated with better OS and CSS. The OS and CSS in patients with HPC with SPM were better than those in patients without SPM (log rank P < 0.0001). The C indexes of the nomogram constructed with ten influencing factors including SPM were 0.681:0.699 for OS and 0.705:0.724 for CSS (training cohort:validation cohort). Conclusion Although the overall risk of SPM in patients with HPC was elevated, SPM did not decrease the OS and CSS in patients with HPC. This finding is inconsistent with clinical observations and thus requires further research and exploration. It possibly because HPC might have a shorter survival time, or the follow-up time was not long enough.
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Affiliation(s)
- Liqing Guo
- Department of Otolaryngology, The Second Affiliated Hospital of Nanchang University, NanChang, 330006, JiangXi, People's Republic of China
| | - Yanpeng Fu
- Department of Otolaryngology, The Second Affiliated Hospital of Nanchang University, NanChang, 330006, JiangXi, People's Republic of China
| | - Chunyu Miao
- Department of Otolaryngology, Nanchang Affiliated Hospital of Sun Yat-Sen University, NanChang, 330009, JiangXi, People's Republic of China
| | - Shuhong Wu
- Department of Otolaryngology, The Second Affiliated Hospital of Nanchang University, NanChang, 330006, JiangXi, People's Republic of China
| | - Yaqiong Zhu
- Department of Otolaryngology, The Second Affiliated Hospital of Nanchang University, NanChang, 330006, JiangXi, People's Republic of China
| | - Yuehui Liu
- Department of Otolaryngology, The Second Affiliated Hospital of Nanchang University, NanChang, 330006, JiangXi, People's Republic of China
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16
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Wu Q, Wang M, Liu Y, Wang X, Li Y, Hu X, Qiu Y, Liang W, Wei Y, Zhong Y. HPV Positive Status Is a Favorable Prognostic Factor in Non-Nasopharyngeal Head and Neck Squamous Cell Carcinoma Patients: A Retrospective Study From the Surveillance, Epidemiology, and End Results Database. Front Oncol 2021; 11:688615. [PMID: 34631523 PMCID: PMC8497986 DOI: 10.3389/fonc.2021.688615] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 09/03/2021] [Indexed: 01/08/2023] Open
Abstract
Objective To investigate the impact of the human papillomavirus (HPV) status on head and neck squamous cell carcinoma (HNSCC) arising from different anatomic subsites. Methods HNSCC patients with known HPV status from the Surveillance, Epidemiology, and End Results (SEER) database between 2010–2015 were included in our analysis. Patients were classified into three categories of HNSCC according to Site recode ICD-O-3/WHO 2008 and Primary Site-labeled, namely, oropharynx, hypopharynx, and nasopharynx. Logistic regression model was conducted to evaluate the relationship between patient characteristics and HPV status. Kaplan-Meier methods and COX regression analysis were used to analyze survival data. Results A total of 9,943 HNSCC patients with known HPV status from the SEER database were enrolled, with 6,829 (68.7%) HPV-positive patients. HPV-positive and HPV-negative HNSCC were distinct and had different clinical and socioeconomic features (all P < 0.001). Primary sites, socioeconomical factors (age, sex, marital status, and race), and pathological features (TNM stage and grade) were closely related with HPV status (all P < 0.001). HPV-positive status was a favorable prognostic marker in HNSCC patients with cancers of the oropharynx and hypopharynx (all P < 0.001), but was not in nasopharyngeal carcinoma patients (P = 0.843). A total of 8,933 oropharyngeal carcinoma (OPC) and 558 hypopharyngeal carcinoma (HPC) patients were divided into the training and validation cohorts with a ratio of 1:1. Significant prognostic factors of the OS yielded by multivariate COX analysis in the training cohort were integrated to construct nomograms for OPC and HPC patients. The prognostic models showed a good discrimination with a C-index of 0.79 ± 0.007 and 0.73 ± 0.023 in OPC and HPC, respectively. Favorable calibration was reflected by the calibration curves. Additionally, corresponding risk classification systems for OPC and HPC patients based on the nomograms were built and could perfectly classify patients into low-risk, intermediated-risk, high-risk groups. OS in the three risk groups was accurately differentiated and showed a good discrimination. Conclusion HPV positivity was associated with an improved survival in HNSCC patients with cancers of the oropharynx and hypopharynx. Nomograms and corresponding risk classification systems were constructed to assist clinicians in evaluating the survival of OPC and HPC patients.
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Affiliation(s)
- Qiuji Wu
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Miao Wang
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Yixin Liu
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Xulong Wang
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Yi Li
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Xiaoyan Hu
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Ye Qiu
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Wenjing Liang
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Yongchang Wei
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Yahua Zhong
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.,Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
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17
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Qiu J, Hu F, Shao T, Guo Y, Dai Z, Nie H, Olasunkanmi OI, Qi Y, Chen Y, Lin L, Zhao W, Zhong Z, Wang Y. Blocking of EGFR Signaling Is a Latent Strategy for the Improvement of Prognosis of HPV-Induced Cancer. Front Oncol 2021; 11:633794. [PMID: 34646755 PMCID: PMC8503613 DOI: 10.3389/fonc.2021.633794] [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: 11/26/2020] [Accepted: 08/19/2021] [Indexed: 01/10/2023] Open
Abstract
Human papillomavirus (HPV) is a double-stranded DNA (dsDNA) virus, and its high-risk subtypes increase cancer risks. However, the mechanism of HPV infection and pathogenesis still remain unclear. Therefore, understanding the molecular mechanisms and the pathogenesis of HPV are crucial in the prevention of HPV-related cancers. In this study, we analyzed cervix squamous cell carcinoma (CESC) and head and neck carcinoma (HNSC) combined data to investigate various HPV-induced cancer common features. We showed that epidermal growth factor receptor (EGFR) was downregulated in HPV-positive (HPV+) cancer, and that HPV+ cancer patients exhibited better prognosis than HPV-negative (HPV-) cancer patients. Our study also showed that TP53 mutation rate is lower in HPV+ cancer than in HPV- cancer and that TP53 can be modulated by HPV E7 protein. However, there was no significant difference in the expression of wildtype TP53 in both groups. Subsequently, we constructed HPV-human interaction network and found that EGFR is a critical factor. From the network, we also noticed that EGFR is regulated by HPV E7 protein and hsa-miR-944. Moreover, while phosphorylated EGFR is associated with a worse prognosis, EGFR total express level is not significantly correlated with prognosis. This indicates that EGFR activation will induce a worse outcome in HPV+ cancer patients. Further enrichment analysis showed that EGFR downstream pathway and cancer relative pathway are diversely activated in HPV+ cancer and HPV- cancer. In summary, HPV E7 protein downregulates EGFR that downregulates phosphorylated EGFR and inhibit EGFR-related pathways which in turn and consequently induce better prognosis.
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Affiliation(s)
- Jianfa Qiu
- Department of Microbiology, Harbin Medical University, Harbin, China
| | - Feifei Hu
- Department of Obstetrics, the First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Tingting Shao
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
| | - Yuqiang Guo
- Department of Microbiology, Harbin Medical University, Harbin, China
| | - Zongmao Dai
- Department of Microbiology, Harbin Medical University, Harbin, China
| | - Huanhuan Nie
- Department of Microbiology, Harbin Medical University, Harbin, China
| | | | - Yue Qi
- Department of Microbiology, Harbin Medical University, Harbin, China
| | - Yang Chen
- Department of Microbiology, Harbin Medical University, Harbin, China
| | - Lexun Lin
- Department of Microbiology, Harbin Medical University, Harbin, China
| | - Wenran Zhao
- Department of Cell Biology, Harbin Medical University, Harbin, China
| | - Zhaohua Zhong
- Department of Microbiology, Harbin Medical University, Harbin, China
| | - Yan Wang
- Department of Microbiology, Harbin Medical University, Harbin, China
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18
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Sharma A, Tang AL, Takiar V, Wise-Draper TM, Langevin SM. Human Papillomavirus and Survival of Sinonasal Squamous Cell Carcinoma Patients: A Systematic Review and Meta-Analysis. Cancers (Basel) 2021; 13:cancers13153677. [PMID: 34359578 PMCID: PMC8345036 DOI: 10.3390/cancers13153677] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/05/2021] [Accepted: 07/17/2021] [Indexed: 12/23/2022] Open
Abstract
Simple Summary Human papillomavirus (HPV) has been associated with multiple cancers in the anogenital and upper aerodigestive tracts. In the head and neck region, HPV-positive cancers are common in oropharynx, with rising incidence and a well-established association with more favorable patient outcomes. However, the relationship with prognosis of sinonasal squamous cell carcinoma (SNSCC) has been much less often studied and is presently unclear. To better elucidate this relationship, we performed a systematic review and meta-analysis of the biomedical literature to determine the aggregate effect across studies. In doing so, we observed significantly better overall survival associated with HPV-positive SNSCC. Therefore, we conclude that HPV testing may be useful for determining patient prognosis and potentially guiding treatment decisions. Abstract Human papillomavirus (HPV) is detectable in a subset of sinonasal squamous cell carcinoma (SNSCC), but the impact on patient outcomes is presently unclear due to a modest number of studies with limited statistical power. Therefore, we conducted a systematic review and meta-analysis to better clarify this relationship. A PubMed search was conducted to identify all studies reporting on overall (OS) or disease-free survival (DFS) for SNSCC by HPV status. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were extracted or, when not provided, indirectly estimated from each manuscript. Summary survival curves for 5-year OS and estimating survival probability by HPV status at pre-specified time intervals from study-specific Kaplan-Meier curves generated 2-year DFS. Log HRs and log CIs were combined across studies to generate summary estimates and a corresponding 95% CIs for OS and DFS. We identified ten unique studies reporting on OS and four for DFS. We observed a significant association between HPV and OS (summary HR = 0.51, 95% CI: 0.38–0.70) with relatively low heterogeneity between studies. These results indicate that HPV is a significant predictor of more favorable survival for SNSCC, and thus may be a useful biomarker for prognostication and, potentially, treatment modulation.
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Affiliation(s)
- Anish Sharma
- Medical Sciences Program, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA;
| | - Alice L. Tang
- Department of Otolaryngology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA;
- University of Cincinnati Cancer Center, Cincinnati, OH 45267, USA; (V.T.); (T.M.W.-D.)
| | - Vinita Takiar
- University of Cincinnati Cancer Center, Cincinnati, OH 45267, USA; (V.T.); (T.M.W.-D.)
- Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
- Cincinnati VA Medical Center, Cincinnati, OH 45220, USA
| | - Trisha M. Wise-Draper
- University of Cincinnati Cancer Center, Cincinnati, OH 45267, USA; (V.T.); (T.M.W.-D.)
- Department of Internal Medicine, Division of Hematology & Oncology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
| | - Scott M. Langevin
- University of Cincinnati Cancer Center, Cincinnati, OH 45267, USA; (V.T.); (T.M.W.-D.)
- Department of Environmental & Public Health Sciences, Division of Epidemiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
- Correspondence:
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19
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Aggarwal N, Yadav J, Chhakara S, Janjua D, Tripathi T, Chaudhary A, Chhokar A, Thakur K, Singh T, Bharti AC. Phytochemicals as Potential Chemopreventive and Chemotherapeutic Agents for Emerging Human Papillomavirus-Driven Head and Neck Cancer: Current Evidence and Future Prospects. Front Pharmacol 2021; 12:699044. [PMID: 34354591 PMCID: PMC8329252 DOI: 10.3389/fphar.2021.699044] [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: 04/22/2021] [Accepted: 06/17/2021] [Indexed: 12/20/2022] Open
Abstract
Head and neck cancer (HNC) usually arises from squamous cells of the upper aerodigestive tract that line the mucosal surface in the head and neck region. In India, HNC is common in males, and it is the sixth most common cancer globally. Conventionally, HNC attributes to the use of alcohol or chewing tobacco. Over the past four decades, portions of human papillomavirus (HPV)-positive HNC are increasing at an alarming rate. Identification based on the etiological factors and molecular signatures demonstrates that these neoplastic lesions belong to a distinct category that differs in pathological characteristics and therapeutic response. Slow development in HNC therapeutics has resulted in a low 5-year survival rate in the last two decades. Interestingly, HPV-positive HNC has shown better outcomes following conservative treatments and immunotherapies. This raises demand to have a pre-therapy assessment of HPV status to decide the treatment strategy. Moreover, there is no HPV-specific treatment for HPV-positive HNC patients. Accumulating evidence suggests that phytochemicals are promising leads against HNC and show potential as adjuvants to chemoradiotherapy in HNC. However, only a few of these phytochemicals target HPV. The aim of the present article was to collate data on various leading phytochemicals that have shown promising results in the prevention and treatment of HNC in general and HPV-driven HNC. The review explores the possibility of using these leads against HPV-positive tumors as some of the signaling pathways are common. The review also addresses various challenges in the field that prevent their use in clinical settings.
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Affiliation(s)
- Nikita Aggarwal
- Molecular Oncology Laboratory, Department of Zoology, Faculty of Science, University of Delhi, Delhi, India
| | - Joni Yadav
- Molecular Oncology Laboratory, Department of Zoology, Faculty of Science, University of Delhi, Delhi, India
| | - Suhail Chhakara
- Molecular Oncology Laboratory, Department of Zoology, Faculty of Science, University of Delhi, Delhi, India
| | - Divya Janjua
- Molecular Oncology Laboratory, Department of Zoology, Faculty of Science, University of Delhi, Delhi, India
| | - Tanya Tripathi
- Molecular Oncology Laboratory, Department of Zoology, Faculty of Science, University of Delhi, Delhi, India
| | - Apoorva Chaudhary
- Molecular Oncology Laboratory, Department of Zoology, Faculty of Science, University of Delhi, Delhi, India
| | - Arun Chhokar
- Molecular Oncology Laboratory, Department of Zoology, Faculty of Science, University of Delhi, Delhi, India
| | - Kulbhushan Thakur
- Molecular Oncology Laboratory, Department of Zoology, Faculty of Science, University of Delhi, Delhi, India
| | - Tejveer Singh
- Molecular Oncology Laboratory, Department of Zoology, Faculty of Science, University of Delhi, Delhi, India
| | - Alok Chandra Bharti
- Molecular Oncology Laboratory, Department of Zoology, Faculty of Science, University of Delhi, Delhi, India
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20
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Burbure N, Handorf E, Ridge JA, Bauman J, Liu JC, Giri A, Galloway TJ. Prognostic significance of human papillomavirus status and treatment modality in hypopharyngeal cancer. Head Neck 2021; 43:3042-3052. [PMID: 34165223 DOI: 10.1002/hed.26793] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 03/02/2021] [Accepted: 06/11/2021] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Management of hypopharynx cancer is often extrapolated from larynx cancer. This report analyses treatment patterns and survival limited to hypopharynx cancer using the National Cancer Database (NCDB). METHODS There are 9314 patients diagnosed with hypopharynx cancer between 2004 and 2016. The association between treatment modality and survival was analyzed using Kaplan-Meier survival curves and multivariable Cox regression. RESULTS Five-year overall survival ranged from 45% for stage I to 21% for stage IVB. Treatment modality did not influence survival in stage I/II. For stage III/IV, chemoradiation and surgery + adjuvant therapy were equivalent. Surgery yielded improved survival for T4 disease. Human papillomavirus (HPV)-positive tumors were present in 21% and were associated with improved hazard ratio of death (0.60, p = <0.0001). CONCLUSIONS Survival is superior for T4 hypopharynx cancer managed with surgery, while treatment modality does not impact outcomes for other T-stages. HPV-positive tumors are associated with improved survival regardless of treatment.
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Affiliation(s)
- Nina Burbure
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Elizabeth Handorf
- Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - John A Ridge
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Jessica Bauman
- Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Jeffrey C Liu
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.,Department of Otolaryngology-Head and Neck Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA
| | - Anshu Giri
- Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Thomas J Galloway
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
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21
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Magnes T, Wagner S, Kiem D, Weiss L, Rinnerthaler G, Greil R, Melchardt T. Prognostic and Predictive Factors in Advanced Head and Neck Squamous Cell Carcinoma. Int J Mol Sci 2021; 22:4981. [PMID: 34067112 PMCID: PMC8125786 DOI: 10.3390/ijms22094981] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 05/03/2021] [Accepted: 05/04/2021] [Indexed: 12/11/2022] Open
Abstract
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease arising from the mucosa of the upper aerodigestive tract. Despite multimodality treatments approximately half of all patients with locally advanced disease relapse and the prognosis of patients with recurrent or metastatic HNSCC is dismal. The introduction of checkpoint inhibitors improved the treatment options for these patients and pembrolizumab alone or in combination with a platinum and fluorouracil is now the standard of care for first-line therapy. However, approximately only one third of unselected patients respond to this combination and the response rate to checkpoint inhibitors alone is even lower. This shows that there is an urgent need to improve prognostication and prediction of treatment benefits in patients with HNSCC. In this review, we summarize the most relevant risk factors in the field and discuss their roles and limitations. The human papilloma virus (HPV) status for patients with oropharyngeal cancer and the combined positive score are the only biomarkers consistently used in clinical routine. Other factors, such as the tumor mutational burden and the immune microenvironment have been highly studied and are promising but need validation in prospective trials.
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Affiliation(s)
- Teresa Magnes
- Oncologic Center, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Paracelsus Medical University, 5020 Salzburg, Austria; (T.M.); (S.W.); (D.K.); (L.W.); (G.R.); (R.G.)
| | - Sandro Wagner
- Oncologic Center, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Paracelsus Medical University, 5020 Salzburg, Austria; (T.M.); (S.W.); (D.K.); (L.W.); (G.R.); (R.G.)
| | - Dominik Kiem
- Oncologic Center, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Paracelsus Medical University, 5020 Salzburg, Austria; (T.M.); (S.W.); (D.K.); (L.W.); (G.R.); (R.G.)
| | - Lukas Weiss
- Oncologic Center, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Paracelsus Medical University, 5020 Salzburg, Austria; (T.M.); (S.W.); (D.K.); (L.W.); (G.R.); (R.G.)
- Cancer Cluster Salzburg, 5020 Salzburg, Austria
- Salzburg Cancer Research Institute-Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), 5020 Salzburg, Austria
| | - Gabriel Rinnerthaler
- Oncologic Center, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Paracelsus Medical University, 5020 Salzburg, Austria; (T.M.); (S.W.); (D.K.); (L.W.); (G.R.); (R.G.)
- Cancer Cluster Salzburg, 5020 Salzburg, Austria
- Salzburg Cancer Research Institute-Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), 5020 Salzburg, Austria
| | - Richard Greil
- Oncologic Center, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Paracelsus Medical University, 5020 Salzburg, Austria; (T.M.); (S.W.); (D.K.); (L.W.); (G.R.); (R.G.)
- Cancer Cluster Salzburg, 5020 Salzburg, Austria
- Salzburg Cancer Research Institute-Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), 5020 Salzburg, Austria
| | - Thomas Melchardt
- Oncologic Center, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Paracelsus Medical University, 5020 Salzburg, Austria; (T.M.); (S.W.); (D.K.); (L.W.); (G.R.); (R.G.)
- Salzburg Cancer Research Institute-Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), 5020 Salzburg, Austria
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22
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Luo XJ, Zheng M, Cao MX, Zhang WL, Huang MC, Dai L, Tang YL, Liang XH. Distinguishable Prognostic miRNA Signatures of Head and Neck Squamous Cell Cancer With or Without HPV Infection. Front Oncol 2021; 10:614487. [PMID: 33643915 PMCID: PMC7902765 DOI: 10.3389/fonc.2020.614487] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 12/08/2020] [Indexed: 02/05/2023] Open
Abstract
Since their discovery in the 1990’s, microRNAs (miRNA) have opened up new vistas in the field of cancer biology and are found to have fundamental roles in tumorigenesis and progression. As head and neck squamous cell carcinoma (HNSCC) with positive human papillomavirus (HPV+) is significantly distinct from its HPV negative (HPV−) counterpart in terms of both molecular mechanisms and clinical prognosis, the current study aimed to separately develop miRNA signatures for HPV+ and HPV− HNSCC as well as to explore the potential functions. Both signatures were reliable for the prediction of prognosis in their respective groups. Then Enrichment analysis was performed to predict the potential biological functions of the signatures. Importantly, combining previous studies and our results, we speculated that HPV+ HNSCC patients with low signature score had better immunity against the tumors and enhanced the sensitivity of therapies leading to improved prognosis, while HPV− HNSCC patients with high signature score acquired resistance to therapeutic approaches as well as dysregulation of cell metabolism leading to poor prognosis. Hence, we believe that the identified signatures respectively for HPV+ and HPV− HNSCC, are of great significance in accessing patient outcomes as well as uncovering new biomarkers and therapeutic targets, which are worth further investigation through molecular biology experiments.
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Affiliation(s)
- Xiao-Jie Luo
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Min Zheng
- Department of Stomatology, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, China
| | - Ming-Xin Cao
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Wei-Long Zhang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Mei-Chang Huang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Li Dai
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Ya-Ling Tang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xin-Hua Liang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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23
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Nissi L, Suilamo S, Kytö E, Vaittinen S, Irjala H, Minn H. Recurrence of head and neck squamous cell carcinoma in relation to high-risk treatment volume. Clin Transl Radiat Oncol 2021; 27:139-146. [PMID: 33665383 PMCID: PMC7902285 DOI: 10.1016/j.ctro.2021.01.013] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 01/30/2021] [Accepted: 01/31/2021] [Indexed: 12/01/2022] Open
Abstract
Distribution of recurrent HNSCC in relation to radiotherapy volume was evaluated. Both p16 positive and negative HNSCC recur in high-risk treatment volume. This indicates potential failure of multimodality imaging to disclose significant disease. A need for biomarkers other than p16 to predict radiosensitivity continues to exist. Background Locoregional recurrence remains a major cause of failure in head and neck squamous cell carcinoma (HNSCC). Human papilloma virus (HPV)-associated HNSCCs generally have a good prognosis but may recur even after standard photon radiotherapy (RT). Another incentive in observing patterns of recurrence is increased use of highly conformal techniques such as proton therapy. We therefore studied geographic distribution of recurrent tumors in relation to the high-risk treatment volume in a cohort of patients with HNSCC receiving combined modality therapy. Methods Medical records of 508 patients diagnosed with HNSCC in 2010–2015 were reviewed. We identified a subgroup that had local and/or regional recurrence at hybrid positron emission tomography (PET)/computed tomography (CT) and/or magnetic resonance imaging (MRI). We adapted p16 as a surrogate marker for HPV-positivity and only patients with known p16 status were eligible for a detailed analysis where recurrent tumor was copied on the planning CT and the dose received by the recurrent tumor volume was determined using dose-volume histograms. Results Twenty-five patients who had received either cisplatin (n = 23) or cetuximab-enhanced (n = 2) RT were identified. 31 locoregional recurrent tumors were detected among 18 p16 negative and 7 p16 positive patients. Of recurrent tumors 14 (45%) were classified as in-field, 5 (16%) as marginal miss, and 12 (39%) as true miss. p16 positive patients had 4 in-field, 2 marginal, and 1 true miss. By contrast, p16 negative patients had 10 in-field, 3 marginal, and 11 true miss recurrences. Conclusions Both p16 positive and negative HNSCC recur in high-risk treatment volume despite the common view of high radiosensitivity of the former. Biomarkers predicting radioresistance should be characterized in p16 positive tumors before widely embarking on de-escalated CRT protocols. Another concern is how to decrease the number of true or marginal misses in p16 negative cases despite multimodality imaging-based target delineation.
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Key Words
- 18F-fluorodeoxyglucose, FDG
- CRT, chemoradiotherapy
- CT, computed tomography
- DFS, disease-free survival
- HNSCC, head and neck squamous cell carcinoma
- HPV, human papilloma virus
- Head and neck cancer
- Human papillomavirus
- IMRT, intensity modulated radiotherapy
- In-field recurrence
- MRI, magnetic resonance imaging
- OS, overall survival
- PET, positron emission tomography
- RT, radiation therapy
- Radioresistance
- Tumor recurrence
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Affiliation(s)
- Linda Nissi
- Department of Oncology, University of Turku and Turku University Hospital, Turku, Finland
| | - Sami Suilamo
- Department of Oncology, University of Turku and Turku University Hospital, Turku, Finland.,Department of Medical Physics, Turku University Hospital, Turku, Finland
| | - Eero Kytö
- Department of Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University Hospital, Turku, Finland
| | - Samuli Vaittinen
- Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland
| | - Heikki Irjala
- Department of Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University Hospital, Turku, Finland
| | - Heikki Minn
- Department of Oncology, University of Turku and Turku University Hospital, Turku, Finland
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24
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Chakravarthy R, Stallings SC, Velez Edwards DR, Zhao SK, Conway D, Rao JS, Aldrich MC, Kobetz E, Wilkins CH. Determinants of stage at diagnosis of HPV-related cancer including area deprivation and clinical factors. J Public Health (Oxf) 2021; 44:18-27. [PMID: 33512511 PMCID: PMC8904191 DOI: 10.1093/pubmed/fdaa246] [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: 01/25/2020] [Revised: 07/24/2020] [Accepted: 12/05/2020] [Indexed: 11/23/2022] Open
Abstract
Background Collecting social determinants of health in electronic health records is time-consuming. Meanwhile, an Area Deprivation Index (ADI) aggregates sociodemographic information from census data. The objective of this study was to ascertain whether ADI is associated with stage of human papillomavirus (HPV)-related cancer at diagnosis. Methods We tested for the association between the stage of HPV-related cancer presentation and ADI as well as the association between stage and the value of each census-based measure using ordered logistic regression, adjusting for age, race and sex. Results Among 3247 cases of HPV-related cancers presenting to an urban academic medical center, the average age at diagnosis was 57. The average stage at diagnosis was Surveillance, Epidemiology and End Results Stage 3. In the study population, 43% of patients were female and 87% were white. In this study population, there was no association between stage of HPV-related cancer presentation and either aggregate or individual census variables. Conclusions These results may reflect insufficient sample size, a lack of socio-demographic diversity in our population, or suggest that simplifying social determinants of health into a single geocoded index is not a reliable surrogate for assessing a patient’s risk for HPV-related cancer.
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Affiliation(s)
| | - Sarah C Stallings
- Department of Medicine, Division of Geriatrics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Digna R Velez Edwards
- Division of Quantitative Sciences, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN, USA.,Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA.,Institute for Medicine and Public Health, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Sifang Kathy Zhao
- Institute for Medicine and Public Health, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Douglas Conway
- Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN, USA
| | - J Sunil Rao
- Department of Public Health Sciences, University of Miami School of Medicine, Miami, FL, USA.,Division of Biostatistics, University of Miami School of Medicine, Miami, FL, USA
| | - Melinda C Aldrich
- Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.,Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Erin Kobetz
- Department of Public Health Sciences, University of Miami School of Medicine, Miami, FL, USA.,Department of Medicine, University of Miami, Coral Gables, FL, USA
| | - Consuelo H Wilkins
- Department of Medicine, Division of Geriatrics, Vanderbilt University Medical Center, Nashville, TN, USA.,Meharry-Vanderbilt Alliance, Nashville, TN, USA.,Office of Health Equity, Vanderbilt University Medical Center, Nashville, TN, USA
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25
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Aggarwal N, Yadav J, Thakur K, Bibban R, Chhokar A, Tripathi T, Bhat A, Singh T, Jadli M, Singh U, Kashyap MK, Bharti AC. Human Papillomavirus Infection in Head and Neck Squamous Cell Carcinomas: Transcriptional Triggers and Changed Disease Patterns. Front Cell Infect Microbiol 2020. [PMID: 33344262 DOI: 10.3389/fcimb.2020.537650,] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of cancers. Collectively, HNSCC ranks sixth in incidence rate worldwide. Apart from classical risk factors like tobacco and alcohol, infection of human papillomavirus (HPV) is emerging as a discrete risk factor for HNSCC. HPV-positive HNSCC represent a distinct group of diseases that differ in their clinical presentation. These lesions are well-differentiated, occur at an early age, and have better prognosis. Epidemiological studies have demonstrated a specific increase in the proportions of the HPV-positive HNSCC. HPV-positive and HPV-negative HNSCC lesions display different disease progression and clinical response. For tumorigenic-transformation, HPV essentially requires a permissive cellular environment and host cell factors for induction of viral transcription. As the spectrum of host factors is independent of HPV infection at the time of viral entry, presumably entry of HPV only selects host cells that are permissive to establishment of HPV infection. Growing evidence suggest that HPV plays a more active role in a subset of HNSCC, where they are transcriptionally-active. A variety of factors provide a favorable environment for HPV to become transcriptionally-active. The most notable are the set of transcription factors that have direct binding sites on the viral genome. As HPV does not have its own transcription machinery, it is fully dependent on host transcription factors to complete the life cycle. Here, we review and evaluate the current evidence on level of a subset of host transcription factors that influence viral genome, directly or indirectly, in HNSCC. Since many of these transcription factors can independently promote carcinogenesis, the composition of HPV permissive transcription factors in a tumor can serve as a surrogate marker of a separate molecularly-distinct class of HNSCC lesions including those cases, where HPV could not get a chance to infect but may manifest better prognosis.
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Affiliation(s)
- Nikita Aggarwal
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Joni Yadav
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Kulbhushan Thakur
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Rakhi Bibban
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Arun Chhokar
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Tanya Tripathi
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Anjali Bhat
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Tejveer Singh
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Mohit Jadli
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Ujala Singh
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Manoj K Kashyap
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India.,Amity Medical School, Stem Cell Institute, Amity University Haryana, Amity Education Valley Panchgaon, Gurugram, India
| | - Alok C Bharti
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
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26
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Aggarwal N, Yadav J, Thakur K, Bibban R, Chhokar A, Tripathi T, Bhat A, Singh T, Jadli M, Singh U, Kashyap MK, Bharti AC. Human Papillomavirus Infection in Head and Neck Squamous Cell Carcinomas: Transcriptional Triggers and Changed Disease Patterns. Front Cell Infect Microbiol 2020; 10:537650. [PMID: 33344262 PMCID: PMC7738612 DOI: 10.3389/fcimb.2020.537650] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 11/02/2020] [Indexed: 02/05/2023] Open
Abstract
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of cancers. Collectively, HNSCC ranks sixth in incidence rate worldwide. Apart from classical risk factors like tobacco and alcohol, infection of human papillomavirus (HPV) is emerging as a discrete risk factor for HNSCC. HPV-positive HNSCC represent a distinct group of diseases that differ in their clinical presentation. These lesions are well-differentiated, occur at an early age, and have better prognosis. Epidemiological studies have demonstrated a specific increase in the proportions of the HPV-positive HNSCC. HPV-positive and HPV-negative HNSCC lesions display different disease progression and clinical response. For tumorigenic-transformation, HPV essentially requires a permissive cellular environment and host cell factors for induction of viral transcription. As the spectrum of host factors is independent of HPV infection at the time of viral entry, presumably entry of HPV only selects host cells that are permissive to establishment of HPV infection. Growing evidence suggest that HPV plays a more active role in a subset of HNSCC, where they are transcriptionally-active. A variety of factors provide a favorable environment for HPV to become transcriptionally-active. The most notable are the set of transcription factors that have direct binding sites on the viral genome. As HPV does not have its own transcription machinery, it is fully dependent on host transcription factors to complete the life cycle. Here, we review and evaluate the current evidence on level of a subset of host transcription factors that influence viral genome, directly or indirectly, in HNSCC. Since many of these transcription factors can independently promote carcinogenesis, the composition of HPV permissive transcription factors in a tumor can serve as a surrogate marker of a separate molecularly-distinct class of HNSCC lesions including those cases, where HPV could not get a chance to infect but may manifest better prognosis.
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Affiliation(s)
- Nikita Aggarwal
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Joni Yadav
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Kulbhushan Thakur
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Rakhi Bibban
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Arun Chhokar
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Tanya Tripathi
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Anjali Bhat
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Tejveer Singh
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Mohit Jadli
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Ujala Singh
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
| | - Manoj K. Kashyap
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
- Amity Medical School, Stem Cell Institute, Amity University Haryana, Amity Education Valley Panchgaon, Gurugram, India
| | - Alok C. Bharti
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India
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27
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Goncalves A, Soper B, Nygård M, Nygård JF, Ray P, Widemann D, Sales AP. Improving five-year survival prediction via multitask learning across HPV-related cancers. PLoS One 2020; 15:e0241225. [PMID: 33196642 PMCID: PMC7668590 DOI: 10.1371/journal.pone.0241225] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 10/11/2020] [Indexed: 12/12/2022] Open
Abstract
Oncology is a highly siloed field of research in which sub-disciplinary specialization has limited the amount of information shared between researchers of distinct cancer types. This can be attributed to legitimate differences in the physiology and carcinogenesis of cancers affecting distinct anatomical sites. However, underlying processes that are shared across seemingly disparate cancers probably affect prognosis. The objective of the current study is to investigate whether multitask learning improves 5-year survival cancer patient survival prediction by leveraging information across anatomically distinct HPV related cancers. Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program database. The study cohort consisted of 29,768 primary cancer cases diagnosed in the United States between 2004 and 2015. Ten different cancer diagnoses were selected, all with a known association with HPV risk. In the analysis, the cancer diagnoses were categorized into three distinct topography groups of varying specificity. The most specific topography grouping consisted of 10 original cancer diagnoses differentiated by the first two digits of the ICD-O-3 topography code. The second topography grouping consisted of cancer diagnoses categorized into six distinct organ groups. Finally, the third topography grouping consisted of just two groups, head-neck cancers and ano-genital cancers. The tasks were to predict 5-year survival for patients within the different topography groups using 14 predictive features which were selected among descriptive variables available in the SEER database. The information from the predictive features was shared between tasks in three different ways, resulting in three distinct predictive models: 1) Information was not shared between patients assigned to different tasks (single task learning); 2) Information was shared between all patients, regardless of task (pooled model); 3) Only relevant information was shared between patients grouped to different tasks (multitask learning). Prediction performance was evaluated with Brier scores. All three models were evaluated against one another on each of the three distinct topography-defined tasks. The results showed that multitask classifiers achieved relative improvement for the majority of the scenarios studied compared to single task learning and pooled baseline methods. In this study, we have demonstrated that sharing information among anatomically distinct cancer types can lead to improved predictive survival models.
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Affiliation(s)
- Andre Goncalves
- Lawrence Livermore National Laboratory, Livermore, CA, United States of America
| | - Braden Soper
- Lawrence Livermore National Laboratory, Livermore, CA, United States of America
| | | | | | - Priyadip Ray
- Lawrence Livermore National Laboratory, Livermore, CA, United States of America
| | - David Widemann
- Lawrence Livermore National Laboratory, Livermore, CA, United States of America
| | - Ana Paula Sales
- Lawrence Livermore National Laboratory, Livermore, CA, United States of America
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28
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Liu X, Chen J, Lu W, Zeng Z, Li J, Jiang X, Gao Y, Gong Y, Wu Q, Xie C. Systematic Profiling of Immune Risk Model to Predict Survival and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma. Front Genet 2020; 11:576566. [PMID: 33193693 PMCID: PMC7596453 DOI: 10.3389/fgene.2020.576566] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 09/21/2020] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND AND PURPOSE Head and neck squamous carcinoma (HNSCC), characterized by immunosuppression, is a group of highly heterogeneous cancers. Although immunotherapy exerts a promising influence on HNSCC, the response rate remains low and varies in assorted primary sites. Immunological mechanisms underlying HNSCC pathogenesis and treatment response are not fully understood. This study aimed to develop a differentially expressed genes (DEGs)-based risk model to predict immunotherapy efficacy and stratify prognosis of HNSCC patients. MATERIALS AND METHODS The expression profiles of HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The tumor microenvironment and immune response were estimated by cell type identification via estimating relative subset of known RNA transcripts (CIBERSORT) and immunophenoscore (IPS). The differential expression pattern based on human papillomavirus status was identified. A DEGs-based prognostic risk model was developed and validated. All statistical analyses were performed with R software (version 3.6.3). RESULTS By using the TCGA database, we identified DKK1, HBEGF, RNASE7, TNFRSF12A, INHBA, and IPIK3R3 as DEGs that were associated with patients' overall survival (OS). Patients were stratified into the high- and low-risk subgroups according to a DEGs-based prognostic risk model. Significant difference in OS was found between the high- and low-risk patients (1.64 vs. 2.18 years, P = 0.0017). In multivariate Cox analysis, the risk model was an independent prognostic factor for OS (hazard radio = 1.06, 95% confidence interval [1.02-1.10], P = 0.004). More CD8+ T cells and regulatory T cells were observed in the low-risk group and associated with a favorable prognosis. The IPS analysis suggested that the low-risk patients possessed a higher IPS score and a higher immunoreactivity phenotype, which were correlated with better immunotherapy response. CONCLUSION Collectively, we established a reliable DEGs-based risk model with potential prognostic value and capacity to predict the immunophenotype of HNSCC patients.
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Affiliation(s)
- Xingyu Liu
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jiarui Chen
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Wei Lu
- Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zihang Zeng
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jiali Li
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Xueping Jiang
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Yanping Gao
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Yan Gong
- Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Qiuji Wu
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Conghua Xie
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China
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Zhang S, Yang S, Xu P, Xu Y, Zhou G, Ou X, Wu R, Lan M, Fontanarosa D, Dowling J, Wang X, Lin S, Yi JL, Sun Y, Hu C, Lang J. Variations of Clinical Target Volume Delineation for Primary Site of Nasopharyngeal Cancer Among Five Centers in China. Front Oncol 2020; 10:1572. [PMID: 32974193 PMCID: PMC7468394 DOI: 10.3389/fonc.2020.01572] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 07/21/2020] [Indexed: 12/13/2022] Open
Abstract
Purpose The purpose of this study is to investigate the current status of clinical target volume (CTV) delineation for primary site of nasopharyngeal cancer (NPC) among five large tertiary cancer centers in China. Materials and Methods The simulation CT and MR images of a patient with T3N2M0 NPC were sent to the centers participating. Fourteen experienced physicians contoured the targets independently, and the outlined structures were compared. The consistency and differences among these 14 CTVs are discussed. Results Two different CTV designs were used in the centers. "One-CTV" design defines one CTV with a dose of 60 Gy, whereas "two-CTV" design has a high-risk CTV with dose of 60 Gy and a medium risk CTV with dose of 54 Gy. We found that the coverage of prophylactic area is very consistent between these two designs. The variances on the coverage of some sites were also significant among physicians, including covering cavernous sinus at un-involved side, posterior space of styloid process, and caudal border on posterior pharyngeal wall. Conclusions Standardization is the main requirement for personalization of care; our study shows that among the 14 physicians in the five centers the coverage of prophylactic areas is in excellent agreement. Two distinct strategies on CTV design are currently being used, and multiple controversies were found, suggesting further optimization of CTV for primary site of NPC is needed.
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Affiliation(s)
- Shichuan Zhang
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Radiation Oncology Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Shuang Yang
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.,Department of Oncology, People's Hospital of Cangxi County, Guangyuan, China
| | - Peng Xu
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Radiation Oncology Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yun Xu
- Department of Radiation Oncology, Fujian Cancer Center, Fuzhou, China
| | - Guanqun Zhou
- Department of Radiation Oncology, School of Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xiaomin Ou
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Runye Wu
- Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union University, Beijing, China
| | - Mei Lan
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Radiation Oncology Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Davide Fontanarosa
- School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.,Institute of Health & Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
| | - Jason Dowling
- Australian e-Health Research Centre, CSIRO, Brisbane, QLD, Australia
| | - Xiaoshen Wang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Shaojun Lin
- Department of Radiation Oncology, Fujian Cancer Center, Fuzhou, China
| | - Jun-Lin Yi
- Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union University, Beijing, China
| | - Ying Sun
- Department of Radiation Oncology, School of Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Chaosu Hu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jinyi Lang
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Radiation Oncology Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
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30
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Janecka-Widła A, Mucha-Małecka A, Majchrzyk K, Halaszka K, Przewoźnik M, Słonina D, Biesaga B. Active HPV infection and its influence on survival in head and neck squamous-cell cancer. J Cancer Res Clin Oncol 2020; 146:1677-1692. [PMID: 32372145 PMCID: PMC7256081 DOI: 10.1007/s00432-020-03218-6] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 04/11/2020] [Indexed: 01/04/2023]
Abstract
Purpose HPV is involved in the development of some head and neck squamous-cell carcinomas (HNSCC). It was suggested that only transcriptionally active virus can induce carcinogenesis, therefore, the aim of our study was to analyze the frequency of active HPV infection, virus type, and its prognostic role in HNSCC patients. Methods Status of active HPV infection was assessed for 155 HNSCC patients based on p16 expression and HPV DNA presence. Univariate and multivariate analyses with Cox proportional regression model were performed to select independent prognostic factors. Results Active HPV infection was detected in 20.65% of patients. We identified 16.0, 40.9 and 1.7% of HPV positive oral cavity, oropharyngeal, and laryngeal cancer cases, respectively. HPV16 was dominant (81.25%) followed by HPV35 (9.38%) and double infections with HPV16 and 35 (6.25%) or HPV35 and 18 (3.12%). Patients with active HPV infection demonstrated significantly higher survival than HPV negative ones (OS 80.89% vs. 37.08%, p = 0.000; DFS 93.0% vs. 53.35%, p = 0.000, respectively). Longer OS and DFS were maintained for infected patients when oropharyngeal and non-oropharyngeal cases were analyzed separately. Interestingly, all patients infected with other than HPV16 types survived 5 years without cancer progression. In the analyzed group of 155 patients the strongest independent favourable prognostic factor for both OS and DFS was HPV presence. Conclusions High prevalence of HPV-driven HNSCC (mostly within oropharynx) was detected, with HPV16 type the most frequent, followed by HPV35 and HPV18. The presence of active HPV infection improved survival of both oropharyngeal and non-oropharyngeal cancer patients and should be taken into account in treatment planning.
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Affiliation(s)
- Anna Janecka-Widła
- Department of Tumour Pathology, Maria Sklodowska-Curie Institute - Oncology Center, Cracow Branch, Cracow, Poland.
| | - Anna Mucha-Małecka
- Department of Radiotherapy, Maria Sklodowska-Curie Institute - Oncology Center, Cracow Branch, Cracow, Poland
| | - Kaja Majchrzyk
- Department of Tumour Pathology, Maria Sklodowska-Curie Institute - Oncology Center, Cracow Branch, Cracow, Poland
| | - Krzysztof Halaszka
- Department of Tumour Pathology, Maria Sklodowska-Curie Institute - Oncology Center, Cracow Branch, Cracow, Poland
| | - Marcin Przewoźnik
- Department of Tumour Pathology, Maria Sklodowska-Curie Institute - Oncology Center, Cracow Branch, Cracow, Poland
| | - Dorota Słonina
- Department of Tumour Pathology, Maria Sklodowska-Curie Institute - Oncology Center, Cracow Branch, Cracow, Poland.,Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Institute - Oncology Center, Gliwice Branch, Gliwice, Poland
| | - Beata Biesaga
- Department of Tumour Pathology, Maria Sklodowska-Curie Institute - Oncology Center, Cracow Branch, Cracow, Poland.,Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Institute - Oncology Center, Gliwice Branch, Gliwice, Poland
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31
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Haider SP, Burtness B, Yarbrough WG, Payabvash S. Applications of radiomics in precision diagnosis, prognostication and treatment planning of head and neck squamous cell carcinomas. CANCERS OF THE HEAD & NECK 2020; 5:6. [PMID: 32391171 PMCID: PMC7197186 DOI: 10.1186/s41199-020-00053-7] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 03/09/2020] [Indexed: 12/15/2022]
Abstract
Recent advancements in computational power, machine learning, and artificial intelligence technology have enabled automated evaluation of medical images to generate quantitative diagnostic and prognostic biomarkers. Such objective biomarkers are readily available and have the potential to improve personalized treatment, precision medicine, and patient selection for clinical trials. In this article, we explore the merits of the most recent addition to the “-omics” concept for the broader field of head and neck cancer – “Radiomics”. This review discusses radiomics studies focused on (molecular) characterization, classification, prognostication and treatment guidance for head and neck squamous cell carcinomas (HNSCC). We review the underlying hypothesis, general concept and typical workflow of radiomic analysis, and elaborate on current and future challenges to be addressed before routine clinical application.
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Affiliation(s)
- Stefan P Haider
- 1Department of Radiology and Biomedical Imaging, Division of Neuroradiology, Yale School of Medicine, New Haven, CT USA.,2Department of Otorhinolaryngology, University Hospital of Ludwig Maximilians University of Munich, Munich, Germany
| | - Barbara Burtness
- 3Department of Internal Medicine, Division of Medical Oncology, Yale School of Medicine, New Haven, CT USA
| | - Wendell G Yarbrough
- 4Department of Otolaryngology/Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, NC USA
| | - Seyedmehdi Payabvash
- 1Department of Radiology and Biomedical Imaging, Division of Neuroradiology, Yale School of Medicine, New Haven, CT USA
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32
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Moan JM, Amdal CD, Malinen E, Svestad JG, Bogsrud TV, Dale E. The prognostic role of 18F-fluorodeoxyglucose PET in head and neck cancer depends on HPV status. Radiother Oncol 2019; 140:54-61. [DOI: 10.1016/j.radonc.2019.05.019] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 05/13/2019] [Accepted: 05/15/2019] [Indexed: 11/25/2022]
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