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Bergqvist L, Virtanen A, Kalliala I, Bützow R, Jakobsson M, Heinonen A, Louvanto K, Dillner J, Nieminen P, Aro K. Predictors for regression and progression of actively surveilled cervical intraepithelial neoplasia grade 2: A prospective cohort study. Acta Obstet Gynecol Scand 2025; 104:763-773. [PMID: 39930620 PMCID: PMC11919748 DOI: 10.1111/aogs.15032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 11/06/2024] [Accepted: 11/22/2024] [Indexed: 03/20/2025]
Abstract
INTRODUCTION To evaluate predicting clinical factors for regression and progression of cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) in young women during two years of active surveillance. MATERIAL AND METHODS This was a single-center prospective observational cohort study. Women under 31 years of age giving written informed consent with histologically confirmed CIN2 were followed with colposcopy, cytology, and biopsies every 6 months up to 24 months. At baseline, HPV genotyping was performed on cervical samples. The rates of regression and progression were recorded for every timepoint and at the end of study overall and stratified according to clinical factors and HPV genotypes at baseline. Risk ratio (RR) was used to estimate the relative risks for regression and progression. The study was registered in the ISRCTN registry (ISRCTN91953024). RESULTS In total, 205/243 (84.4%) women completed the study. Complete regression (normal histology and/or normal or atypical squamous cells of undetermined significance (ASC-US) cytology) was detected in 64.4.% (n = 132) while 16.1% (n = 33) of the lesions progressed to CIN grade 3 (CIN3) or worse including 31 CIN3 cases, one adenocarcinoma in situ and one cervical cancer case. Factors associated with progression were initial large (>50% of the transformation zone) lesion size, risk ratio (RR) 3.06 (95% confidence interval (CI) 1.40-6.69), and high-grade referral cytology RR 4.73 (95% CI 1.18-19.03). Compared with baseline HPV negativity or having only low-risk HPV genotypes present, high-risk HPV (hrHPV) positivity was associated with lower likelihood of regression RR 0.74 (95% CI 0.60-0.91). Age, cigarette smoking, use of combined oral contraceptives or baseline high-risk HPV genotype, including HPV16, were not associated with the outcomes. CONCLUSIONS The majority of CIN2 lesions regress in young women. Women with large lesions and/or high-grade referral cytology should perhaps more often be treated instead of active surveillance. Initial hrHPV genotype does not appear to predict outcomes while not harboring hrHPV favors regression.
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Affiliation(s)
- Laura Bergqvist
- Department of Obstetrics and GynecologyUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
| | - Anni Virtanen
- Department of PathologyUniversity of Helsinki and HUS Diagnostic Center, Helsinki University HospitalHelsinkiFinland
| | - Ilkka Kalliala
- Department of Obstetrics and GynecologyUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
- Department of Metabolism, Digestion and Reproduction, Faculty of MedicineInstitute of Reproductive and Developmental Biology, Imperial CollegeLondonUK
| | - Ralf Bützow
- Department of PathologyUniversity of Helsinki and HUS Diagnostic Center, Helsinki University HospitalHelsinkiFinland
| | - Maija Jakobsson
- Department of Obstetrics and GynecologyHyvinkää Hospital, Helsinki University Hospital and University of HelsinkiHyvinkääFinland
| | - Annu Heinonen
- Department of Obstetrics and GynecologyUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
| | - Karolina Louvanto
- Department of Obstetrics and GynecologyTampere University HospitalTampereFinland
- Department of Obstetrics and Gynecology, Faculty of Medicine and Health TechnologyTampere UniversityTampereFinland
| | - Joakim Dillner
- Department of Laboratory MedicineKarolinska InstituteStockholmSweden
| | - Pekka Nieminen
- Department of Obstetrics and GynecologyUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
| | - Karoliina Aro
- Department of Obstetrics and GynecologyUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
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Liana P, Syahbiran HG, Sari NP, Rahadiyanto KY, Nurwany R, Nurhidayat W, Umar TP. Haematology results, inflammatory haematological ratios, and inflammatory indices in cervical cancer: How is the difference between cancer stage? World J Exp Med 2025; 15:96988. [PMID: 40115758 PMCID: PMC11718581 DOI: 10.5493/wjem.v15.i1.96988] [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: 05/20/2024] [Revised: 10/22/2024] [Accepted: 11/01/2024] [Indexed: 12/26/2024] Open
Abstract
BACKGROUND Cervical cancer is a prevalent form of cancer affecting women worldwide and it is the second most common cancer among women in Indonesia, accounting for 8.5% of all cancer-related deaths. Cervical cancer progression can be evaluated through laboratory tests to detect anaemia, an increased platelet count, and elevated inflammatory markers, therefore, effective laboratory examination is crucial for early detection and treatment of cervical cancer. AIM To evaluate the association between laboratory findings (haematology, haematology index, and inflammatory index) and the clinical stage of cervical cancer. METHODS This cross-sectional study analyzed adult cervical cancer patients' data from medical records and laboratory results including sociodemographic status, histopathological finding, clinical stage, and complete haematology examination. Numerical data was analyzed by the one-way ANOVA (normal data distribution), while the Kruskal-Wallis test was used for non-parametric data (abnormal distribution), followed by appropriate post-hoc analysis. The categorical data was analyzed by the Chi-square or Fisher Exact tests. The significance level was established at a P value < 0.05. RESULTS This study involved the data of 208 adult cervical cancer patients and found no association between age, marital history, parity history, hormonal contraceptive use and cervical cancer stages. There were significant differences in the clinical laboratory test results based on the clinical stage of cervical cancer, including haemoglobin levels (P < 0.001), leucocytes (P < 0.001), neutrophils (P < 0.001), monocytes (P = 0.002), lymphocytes (P = 0.006), platelets (P < 0.001), neutrophil-lymphocyte ratio/NLR (P < 0.001), lymphocyte-monocyte ratio/LMR (P < 0.001), and platelet-lymphocyte ratio/PLR (P < 0.001). There were also significant differences in the systemic inflammatory index (SII) and systematic inflammatory response index (SIRI) between stage III + IV cervical cancer and stage II (SII P < 0.001; SIRI P = 0.001) and stage I (SII P < 0.001; SIRI P = 0.016), associated with the shifts in previously mentioned complete haematological values with cancer advancement. CONCLUSION The haematological parameters, inflammatory haematological ratios, and inflammatory indices exhibited significant differences between cervical cancer stages, therefore these tests can be utilized to evaluate cervical cancer progression.
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Affiliation(s)
- Phey Liana
- Department of Clinical Pathology, Faculty of Medicine, Universitas Sriwijaya-Dr. Mohammad Hoesin General Hospital, Palembang 30114, Sumatera Selatan, Indonesia
| | - Hanif Gusneri Syahbiran
- Department of Medicine Programme, Faculty of Medicine, Universitas Sriwijaya, Palembang 30114, Sumatera Selatan, Indonesia
| | - Nurmalia Purnama Sari
- Department of Clinical Pathology, Faculty of Medicine, Universitas Sriwijaya-Dr. Mohammad Hoesin General Hospital, Palembang 30114, Sumatera Selatan, Indonesia
| | - Kemas Yakub Rahadiyanto
- Department of Clinical Pathology, Faculty of Medicine, Universitas Sriwijaya, Palembang 30114, Sumatera Selatan, Indonesia
| | - Raissa Nurwany
- Department of Physiology and Medical Physics, Faculty of Medicine, Universitas Sriwijaya, Palembang 30114, Sumatera Selatan, Indonesia
| | - Wahyudi Nurhidayat
- Department of Radiotherapy, Dr. Mohammad Hoesin General Hospital, Palembang 30114, Sumatera Selatan, Indonesia
| | - Tungki Pratama Umar
- Division of Surgery and Interventional Science, Faculty of Medical Sciences, University College London, London WC1E 6BT, United Kingdom
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Stolnicu S, Allison D, Patrichi A, Flynn J, Iasonos A, Soslow RA. Invasive Squamous Cell Carcinoma of the Cervix: A Review of Morphological Appearances Encountered in Human Papillomavirus-associated and Papillomavirus-independent Tumors and Precursor Lesions. Adv Anat Pathol 2024; 31:1-14. [PMID: 37638549 PMCID: PMC10841279 DOI: 10.1097/pap.0000000000000411] [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] [Indexed: 08/29/2023]
Abstract
Cervical cancer is the fourth most common cancer among women globally. Historically, human papillomavirus (HPV) infection was considered necessary for the development of both precursor and invasive epithelial tumors of the cervix; however, studies in the last decade have shown that a significant proportion of cervical carcinomas are HPV-independent (HPVI). The 2020 World Health Organization (WHO) Classification of Female Genital Tumors separates both squamous cell carcinomas (SCCs) and endocervical adenocarcinomas (ECAs) by HPV status into HPV-associated (HPVA) and HPVI tumors. The classification further indicates that, in contrast to endocervical adenocarcinomas, HPVI and HPVA SCCs cannot be distinguished by morphological criteria alone and suggests that HPV testing or correlates thereof are required for correct classification. Moreover, while HPVA SCC precursor lesions (ie, high-grade squamous intraepithelial lesion) are well known and characterized, precursors to HPVI SCCs have only been described recently in a small number of cases. We studied 670 cases of SCCs from the International Squamous Cell Carcinoma Project (ISCCP) to analyze the reproducibility of recognition of invasive SCC growth patterns, presence of lymphovascular space invasion, tumor grade, and associations with patient outcomes. Consistent with previous studies, we found histologic growth patterns and tumor types had limited prognostic implications. In addition, we describe the wide morphologic spectrum of HPVA and HPVI SCCs and their precursor lesions, including tumor growth patterns, particular and peculiar morphologic features that can lead to differential diagnoses, and the role of ancillary studies in the diagnosis of these tumors.
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Affiliation(s)
- Simona Stolnicu
- Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology “Gh E Palade” of Targu Mures, Targu Mures, Romania
| | - Douglas Allison
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andrei Patrichi
- Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology “Gh E Palade” of Targu Mures, Targu Mures, Romania
| | - Jessica Flynn
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alexia Iasonos
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Robert A Soslow
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Gilham C, Sargent A, Crosbie EJ, Peto J. Long-term risks of invasive cervical cancer following HPV infection: follow-up of two screening cohorts in Manchester. Br J Cancer 2023; 128:1933-1940. [PMID: 36959379 PMCID: PMC10147679 DOI: 10.1038/s41416-023-02227-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 02/15/2023] [Accepted: 03/02/2023] [Indexed: 03/25/2023] Open
Abstract
BACKGROUND Long-term follow-up of large cohorts is needed to determine the effects of HPV and screening on CIN3 (grade 3 cervical intraepithelial neoplasia) and ICC (invasive cervical cancer). METHODS Women were recruited when attending for routine cervical screening in Greater Manchester, UK: 1987-93 for the Manchester Cohort (MC: 47,625 women) and 2001-03 for the ARTISTIC Cohort (AC: 24,496 women). Both were followed through national registration for cancer incidence and mortality to 2020. RESULTS Risk patterns following HPV infection differed for CIN3 and ICC. Risk of ICC in the MC rises for 30 years following a single positive HPV test, reaching 2.5% (95% CI: 1.3-4.5%). A similar pattern was seen in the AC, but the risks of cancer were approximately halved. CIN3 was diagnosed much sooner in the AC due to more efficient cytology. More sensitive HPV testing was able to better predict future risk. CONCLUSION The sensitivity of HPV testing and cytology influences the CIN3 detection rate. Sensitive HPV testing enables effective risk stratification. Increased risk of ICC is observed 15-30 years after HPV infection. Women testing HPV + should be followed until their infection clears. Discharging women from screening programmes whilst they remain HPV + may not be safe, even if cytology and colposcopy tests are normal.
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Affiliation(s)
- Clare Gilham
- London School of Hygiene & Tropical Medicine, London, UK.
| | - Alexandra Sargent
- Cytology Department, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester, UK
| | - Emma J Crosbie
- Division of Gynaecology, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
- Division of Cancer Sciences, University of Manchester, Faculty of Biology, Medicine and Health, Manchester, UK
| | - Julian Peto
- London School of Hygiene & Tropical Medicine, London, UK
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Rousset-Jablonski C, Mekki Y, Denis A, Reynaud Q, Nove-Josserand R, Durupt S, Touzet S, Perceval M, Ray-Coquard I, Golfier F, Durieu I. Human papillomavirus prevalence, persistence and cervical dysplasia in females with cystic fibrosis. J Cyst Fibros 2022:S1569-1993(22)01415-1. [DOI: 10.1016/j.jcf.2022.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 11/14/2022] [Accepted: 11/27/2022] [Indexed: 12/15/2022]
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Buono-Michel C, Mancini J, Planta M, Agostini A, Carcopino X. [Outcome of women younger than 30 years of age followed for untreated high-grade cervical intraepithelial lesion]. GYNECOLOGIE, OBSTETRIQUE, FERTILITE & SENOLOGIE 2022; 50:610-614. [PMID: 35513265 DOI: 10.1016/j.gofs.2022.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 04/05/2022] [Accepted: 04/19/2022] [Indexed: 06/14/2023]
Abstract
OBJECTIVES To assess the probability of spontaneous regression of high grade cervical intraepithelial neoplasia (HGCIN) in women under 30 and the predictive factors for such evolution. METHODS We conducted a bicentric retrospective study. A total of 98 patients under 30 and with untreated HGCIN were included from 01/01/2010 to 31/12/2019. For each patient, the initial clinical and colposcopic characteristics were systematically documented. In compliance with French guidelines, these patients were offered repeated 6-months colposcopic follow-up for 2years. The endpoint was the occurrence of spontaneous regression of the HGCIN defined by normalization of colposcopy, and/or a negative biopsy and/or a negative HPV test or histological regression to low grade CIN, or a colposcopy showing simple minor abnormalities requiring no biopsy. RESULTS Spontaneous HGCIN regression was observed in 37/98 patients. The median follow-up was of 16 (10.5-24.3) months. Predictive factors for spontaneous regression were: minor initial cytological abnormalities (HR=3.4; 95% CI: 1.02-11.05) and grade 1 atypical transformation at initial colposcopy (TAG1) (HR=2.3; 95% CI: 1.1-4.7). CONCLUSION Before 30, the probability of spontaneous regression of HGCIN exists but remains low. Predictive factors for such evolution are minor initial cytological abnormalities and TAG1 colposcopic impression.
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Affiliation(s)
- C Buono-Michel
- Service de gynécologie-obstétrique, hôpital Nord, chemin des Bourrely, 13915 Marseille cedex 20, France
| | - J Mancini
- Aix-Marseille université, INSERM, IRD, AP-HM, UMR1252, SESSTIM, department of public health (BIOSTIC), hôpital de la Timone, Marseille, France; Département de santé publique, hôpital de la Timone, 264, rue Saint-Pierre, 13395 Marseille cedex 5, France
| | - M Planta
- Aix-Marseille université, INSERM, IRD, AP-HM, UMR1252, SESSTIM, department of public health (BIOSTIC), hôpital de la Timone, Marseille, France; Département de santé publique, hôpital de la Timone, 264, rue Saint-Pierre, 13395 Marseille cedex 5, France
| | - A Agostini
- Service de gynécologie-obstétrique, hôpital de la Conception, 147, boulevard Baille, 13005 Marseille, France
| | - X Carcopino
- Department of obstetrics and gynaecology, hôpital Nord, AP-HM, Aix-Marseille university (AMU), université Avignon, CNRS, IRD, IMBE UMR 7263, 13397 Marseille, France; Service de gynécologie-obstétrique, hôpital Nord, chemin des Bourrely, 13915 Marseille cedex 20, France.
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Boyles GP, Baek J, Pandit R, Cosgrove CM, Bixel KL. An investigation into human papillomavirus (HPV) vaccination for patients undergoing surgery for high-grade cervical or vulvar dysplasia. Gynecol Oncol Rep 2022; 41:101001. [PMID: 35603128 PMCID: PMC9120215 DOI: 10.1016/j.gore.2022.101001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 05/05/2022] [Accepted: 05/09/2022] [Indexed: 11/29/2022] Open
Abstract
HPV vaccination is not consistently offered (31.3%) to patients being treated for high-grade cervical or vulvar dysplasia. Patients undergoing surgery for HPV-related dysplasia are likely to accept HPV vaccination (65.6%). The rate at which adjuvant HPV vaccination is offered may improve over time. Introduction Eligibility for the human papillomavirus (HPV) vaccine now includes adults 27 through 45 years. It has not been reported how providers are addressing HPV vaccination in patients with existing preinvasive disease. Our objectives were to determine the rates at which vaccination is offered to and received by patients undergoing surgery for high-grade cervical or vulvar dysplasia. Materials and Methods This was a single-institution retrospective cohort study including patients ages 18 through 45 years undergoing surgery for high-grade cervical or vulvar dysplasia from 10/2018 to 2/2020. Our primary outcome was the rate at which HPV vaccination was discussed at the pre- and/or post-operative visits. The secondary outcome was the rate of vaccine uptake in these individuals. Characteristics of those offered HPV vaccination were compared to those not offered vaccination. Results Of the 115 patients included, 36 (31.3%) had HPV vaccination addressed in the perioperative setting. Thirty-two of these patients had never been vaccinated, and 21 of these (65.6%) went on to receive partial or complete HPV vaccination. Those in whom HPV vaccination was addressed were more likely to be under 27 years (RR 3.2; 95% CI 2.1–4.8) and less likely to be smokers (RR 0.5; 95% CI 0.2–0.9) or have prior excisional procedures (RR 0.3; 95% CI 0.1–0.9). The absolute rate of discussing HPV vaccination with patients improved from 26.0% within six months of vaccine age eligibility expansion, to 35.4% after six months (P = 0.32). Conclusions Providers did not consistently address HPV vaccination among patients being treated for high-grade cervical or vulvar dysplasia despite the potential benefits. However, a high proportion of these patients are amenable to vaccination. Quality improvement initiatives are warranted to increase the rate of HPV vaccine counseling in this context.
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Affiliation(s)
- Glenn P. Boyles
- The Ohio State University Wexner Medical Center, Department of Obstetrics and Gynecology, Columbus, OH, USA
- Corresponding author at: The Ohio State University Wexner Medical Center, Department of Obstetrics and Gynecology, 410 West 10 Avenue, Columbus, OH 43210, USA.
| | - Jae Baek
- The Ohio State University College of Medicine, Columbus, OH, USA
| | - Radhika Pandit
- The Ohio State University College of Medicine, Columbus, OH, USA
| | - Casey M. Cosgrove
- The Ohio State University and Arthur G. James Cancer Hospital and Solove Research Institute, Division of Gynecologic Oncology, Columbus, OH, USA
| | - Kristin L. Bixel
- The Ohio State University and Arthur G. James Cancer Hospital and Solove Research Institute, Division of Gynecologic Oncology, Columbus, OH, USA
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Anastasiou E, McCarthy KJ, Gollub EL, Ralph L, van de Wijgert JH, Jones HE. The relationship between hormonal contraception and cervical dysplasia/cancer controlling for human papillomavirus infection: A systematic review. Contraception 2022; 107:1-9. [PMID: 34752778 PMCID: PMC8837691 DOI: 10.1016/j.contraception.2021.10.018] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 10/27/2021] [Accepted: 10/28/2021] [Indexed: 11/03/2022]
Abstract
OBJECTIVE Studies on the effect of long-term use of combined oral contraceptives (COCs) on cervical dysplasia and/or cancer risk have been inconsistent. Less is known about the effects of other forms of hormonal contraception (HC). We examine whether HC use increases the risk of incident cervical intraepithelial neoplasia (CIN) 2, 3 and/or cancer after accounting for preexisting human papillomavirus (HPV) infection. STUDY DESIGN Systematic review of prospective studies on HC use as risk factor for cervical dysplasia with HPV infection documented prior to outcome assessment including PubMed and EMBASE records between January 2000 and February 2020 (Prospero #CRD42019130725). RESULTS Among nine eligible studies, seven described recency and type of HC use and therefore comprise the primary analysis; two studies limit comparisons to ever versus never use and are summarized separately. All seven studies explored the relationship between oral contraceptive (OC) use and cervical dysplasia/cancer incidence: two found increased risk (adjusted odds ratio, aOR = 1.5-2.7), one found no association but decreased risk when restricted to women with persistent HPV (adjusted hazard ratio = 0.5), and four found no association. None of the seven studies differentiated between COC and progestin-only pills (POPs) by use recency or duration. The only study that included injectable progestin-only contraception (DMPA) found increased CIN3 incidence among current versus never users (aOR = 1.6). The one study that included Norplant found no association. Two studies included intrauterine device (IUD) use, but did not differentiate between hormonal and copper IUDs, and found no association. CONCLUSION We found no consistent evidence that OC use is associated with increased risk for cervical dysplasia/cancer after controlling for HPV infection. There were too few studies of progestin-only injectables, implants or IUDs to assess their effect on cervical dysplasia/cancer risk. IMPLICATIONS Use of single self-reported HC measures and insufficient distinction by hormonal constituent cloud our understanding of whether some HCs increase risk for cervical cancer. Methodologically rigorous studies with distinct HCs measured as time-varying exposures are needed to inform cervical cancer prevention efforts and improve our understanding of cervical cancer etiology.
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Affiliation(s)
- Elle Anastasiou
- City University of New York (CUNY) Graduate School of Public Health and Health Policy, 55 W. 125th St., New York, NY 10027, USA
| | - Katharine J. McCarthy
- City University of New York (CUNY) Graduate School of Public Health and Health Policy, 55 W. 125th St., New York, NY 10027, USA
| | - Erica L. Gollub
- College of Health Professions, Health Science Program, Pace University, 861 Bedford Rd, Pleasantville, NY 10570, USA
| | - Lauren Ralph
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, 1330 Broadway Suite 1100 Oakland CA 94612 USA
| | - Janneke H.H.M. van de Wijgert
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, Stratenum room 7.127, 3584 Utrecht, Netherlands
| | - Heidi E. Jones
- City University of New York (CUNY) Graduate School of Public Health and Health Policy, 55 W. 125th St., New York, NY 10027, USA,CUNY Institute for Implementation Science in Public Health, 55 W. 125th St., New York, NY 10027, USA
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Sethi S, Ju X, Antonsson A, Canfell K, Smith MA, Garvey G, Hedges J, Jamieson L. Oral HPV infection among Indigenous Australians; incidence, persistence and clearance at 12-months follow-up. Cancer Epidemiol Biomarkers Prev 2021; 31:604-613. [PMID: 34937792 DOI: 10.1158/1055-9965.epi-21-1056] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Revised: 10/19/2021] [Accepted: 12/13/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Persistent oral human papillomavirus (HPV) infection is a risk factor for oropharyngeal squamous cell carcinoma (OPSCC). Indigenous Australians have a higher rate of OPSCC than non-Indigenous Australians. Risk factors for oral HPV persistence among Indigenous Australians are poorly understood. METHODS Participants provided information on socio-demographic characteristics, health-related behaviours including tobacco and alcohol use and sexual history. Participants additionally provided saliva samples for microbial genotyping. Negative log binomial regression models were used to evaluate indicators on incident, persistent and cleared oral HPV infection at 12 months follow-up. RESULTS Of the 1,011 participants recruited at baseline, 321 (35.3%) testing positive for any oral HPV infection. At 12-month follow up, saliva samples were obtained from 743 participants (73.5%). Among the 584 participants, 24 (42.6%) had no oral HPV infection at both time points, 130 (22.2%) had new (incident) oral HPV infection at 12 months, 130 (22.2%) had persistent oral HPV infection (i.e. present at both baseline and 12-months), and 75 (12.8%) had oral HPV infection clearance from baseline to 12-months. Rural location of residence and ever received oral sex were significantly associated with persistence of oral HPV infection. CONCLUSIONS The incidence of oral HPV infection at both baseline and 12-month follow-up was high. IMPACT There are currently no studies available which have assessed oral HPV infection incidence, persistence and clearance amongst Indigenous populations in Australia or even at a global level. The study has been able to identify risk factors associated with potential malignant changes in the oropharynx among Indigenous Australians.
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Affiliation(s)
- Sneha Sethi
- Adelaide Dental School, University of Adelaide
| | - Xiangqun Ju
- Adelaide Dental School, University of Adelaide
| | | | - Karen Canfell
- The Daffodil Centre, The University of Sydney, A Joint Venture with Cancer Council NSW, University of Sydney
| | | | - Gail Garvey
- School of Public Health, University of Queensland
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Katerji M, Duerksen-Hughes PJ. DNA damage in cancer development: special implications in viral oncogenesis. Am J Cancer Res 2021; 11:3956-3979. [PMID: 34522461 PMCID: PMC8414375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 02/04/2021] [Indexed: 06/13/2023] Open
Abstract
DNA lesions arise from a combination of physiological/metabolic sources and exogenous environmental influences. When left unrepaired, these alterations accumulate in the cells and can give rise to mutations that change the function of important proteins (i.e. tumor suppressors, oncoproteins), or cause chromosomal rearrangements (i.e. gene fusions) that also result in the deregulation of key cellular molecules. Progressive acquisition of such genetic changes promotes uncontrolled cell proliferation and evasion of cell death, and hence plays a key role in carcinogenesis. Another less-studied consequence of DNA damage accumulating in the host genome is the integration of oncogenic DNA viruses such as Human papillomavirus, Merkel cell polyomavirus, and Hepatitis B virus. This critical step of viral-induced carcinogenesis is thought to be particularly facilitated by DNA breaks in both viral and host genomes. Therefore, the impact of DNA damage on carcinogenesis is magnified in the case of such oncoviruses via the additional effect of increasing integration frequency. In this review, we briefly present the various endogenous and exogenous factors that cause different types of DNA damage. Next, we discuss the contribution of these lesions in cancer development. Finally, we examine the amplified effect of DNA damage in viral-induced oncogenesis and summarize the limited data existing in the literature related to DNA damage-induced viral integration. To conclude, additional research is needed to assess the DNA damage pathways involved in the transition from viral infection to cancer. Discovering that a certain DNA damaging agent increases the likelihood of viral integration will enable the development of prophylactic and therapeutic strategies designed specifically to prevent such integration, with an ultimate goal of reducing or eliminating these viral-induced malignancies.
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Affiliation(s)
- Meghri Katerji
- Department of Basic Science, Loma Linda University School of Medicine Loma Linda, CA 92354, USA
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Distribution of HPV Genotypes Differs Depending on Behavioural Factors among Young Women. Microorganisms 2021; 9:microorganisms9040750. [PMID: 33918429 PMCID: PMC8066411 DOI: 10.3390/microorganisms9040750] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 03/28/2021] [Accepted: 03/30/2021] [Indexed: 11/23/2022] Open
Abstract
Risk factors for the different human papillomavirus (HPV) genotypes are not well understood, although the risk of cancer is known to vary among them. Our aim was to evaluate the association of diverse behavioral and reproductive factors with genotype-specific HPV prevalence among 879 unvaccinated women aged 18–75 years referred to the colposcopy clinic at Helsinki University Hospital in Finland. Cervical swabs for HPV genotyping were collected in the first visit and assessed for 34 high-risk (hr) and low-risk (lr) HPV genotypes. Participants completed a questionnaire on behavioral, reproductive, and lifestyle factors. Differences in genotype-specific HPV prevalence were analyzed overall and in age groups using binary logistic regression. Smoking was associated with higher prevalence in HPV16 compared with other hrHPV genotypes together with decreasing age, being highest among younger women <30 years old, odds ratio (OR) 3.74 (95% CI 1.42–9.88). The later the sexual debut, the more it seemed to protect from HPV16 infection. The best protection was achieved when the sexual debut took place at >20 years of age, with an OR of 0.43 (95% CI 0.23–0.83). This association was not seen with other hrHPV genotypes. Methods of contraception seemed not to have an effect on hrHPV positivity, regardless of the HPV genotype. The genotype specific hrHPV prevalence differs, depending on behavioral factors, especially among younger women referred to colposcopy.
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Medina-Jiménez AK, Monroy-Torres R. Repurposing Individualized Nutritional Intervention as a Therapeutic Component to Prevent the Adverse Effects of Radiotherapy in Patients With Cervical Cancer. Front Oncol 2020; 10:595351. [PMID: 33364195 PMCID: PMC7754884 DOI: 10.3389/fonc.2020.595351] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Accepted: 10/19/2020] [Indexed: 11/26/2022] Open
Abstract
Worldwide, cervical cancer was the fourth leading cause of cancer death among women, while in Mexico was the second cause (5.28%). Cancer patients receiving chemotherapy and radiotherapy have a high risk of malnutrition secondary to the disease and treatment, affects the patient's overall, with adverse effects on gastrointestinal symptoms. These use affects the medical therapy. The aim of the present study was to evaluate the benefits on individualized nutritional therapy on decrease weight loss and gastrointestinal adverse effects and to consider these outcomes in pharmacology research, especially in repurposing drugs. We conducted a longitudinal design with two comparation groups with medical diagnosis of cervical cancer and received radiotherapy weekly, 1) the intervention group (nutritional intervention and counseling -INC-) with 20 participants and 2) control group (retrospective cohort -CG-) with 9 participants. Weekly body composition, dietary intake, adverse effects (gastrointestinal symptoms), glucose, hemoglobin, and blood pressure were analyzed during 4 to 5 weeks. Both groups had weight loss weekly (p = 0.013 and p = 0.043 respectively) but the CG vs INC presented loss fat-free mass ≥500g in 67 and of 37% respectively. By the end of the intervention a 25% of the INC group had <10 g/dL of hemoglobin vs 60% for the CG. To compare the dietary intake of vitamins (A and folic acid), fiber (p = 0.006), iron (p = 0.03) and energy (mainly carbohydrates) (p = 0.04) were according to the recommendations in INC group (p>0.05). The number needed to treat was 4 (95% CI, 2 to 13). The nutritional intervention and counseling weekly during radiotherapy in cervical cancer to maintain/improve muscle mass, hemoglobin, and dietary intake above 70% of the recommendations for INC group compared to the evidence. Adequate nutritional status was maintained and decrease the rate of complications, mainly gastrointestinal symptoms, in INC group. The efficacy of drug repurposing can improve through individualized nutritional therapy for preventing adverse effects of radiotherapy in patients with cervical cancer.
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Affiliation(s)
- Ana Karen Medina-Jiménez
- Laboratory of Environmental Nutrition and Food Safety, Medicine and Nutrition Department, University of Guanajuato, Guanajuato, Mexico
- Observatorio Universitario de Seguridad Alimentaria y Nutricional del Estado de Guanajuato, Guanajuato, Mexico
| | - Rebeca Monroy-Torres
- Laboratory of Environmental Nutrition and Food Safety, Medicine and Nutrition Department, University of Guanajuato, Guanajuato, Mexico
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Prevalence of genital HPV infection in STI and healthy populations and risk factors for viral persistence. Eur J Clin Microbiol Infect Dis 2020; 40:885-888. [PMID: 33067736 DOI: 10.1007/s10096-020-04073-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 10/14/2020] [Indexed: 10/23/2022]
Abstract
Human papillomavirus (HPV) is a well-established carcinogenic agent. This study aimed to assess prevalence and persistence rate of genital HPV infection in sexually transmitted infections (STIs) patients and healthy subjects. The risk factors influencing the persistence of genital HPV infection were also investigated. The samples were collected with the ThinPrep liquid-based cytology system. Among the HPV-positive patients, those consenting were retested after 12 months. Overall, 145/292 subjects proved HPV positive with a higher prevalence (51%) in STI than in healthy population (43%). The persistence of genital HPV infection was statistically associated with female gender, HR-HPV infection, smoking, and Ureaplasma parvum infection.
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Role of Epstein-Barr Virus and Human Papillomavirus Coinfection in Cervical Cancer: Epidemiology, Mechanisms and Perspectives. Pathogens 2020; 9:pathogens9090685. [PMID: 32839399 PMCID: PMC7557835 DOI: 10.3390/pathogens9090685] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 08/16/2020] [Accepted: 08/18/2020] [Indexed: 12/24/2022] Open
Abstract
High-risk human papillomavirus (HR-HPV) is etiologically associated with the development and progression of cervical cancer, although other factors are involved. Epstein-Barr virus (EBV) detection in premalignant and malignant tissues from uterine cervix has been widely reported; however, its contribution to cervical cancer development is still unclear. Here, a comprehensive analysis regarding EBV presence and its potential role in cervical cancer, the frequency of EBV/HR-HPV coinfection in uterine cervix and EBV infection in tissue-infiltrating lymphocytes were revised. Overall, reports suggest a potential link of EBV to the development of cervical carcinomas in two possible pathways: (1) Infecting epithelial cells, thus synergizing with HR-HPV (direct pathway), and/or (2) infecting tissue-infiltrating lymphocytes that could generate local immunosuppression (indirect pathway). In situ hybridization (ISH) and/or immunohistochemical methods are mandatory for discriminating the cell type infected by EBV. However, further studies are needed for a better understanding of the EBV/HR-HPV coinfection role in cervical carcinogenesis.
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High prevalence of human papillomavirus type 66 in low-grade cervical lesions of Mexican women. Arch Virol 2020; 165:2633-2640. [PMID: 32812092 DOI: 10.1007/s00705-020-04771-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 07/07/2020] [Indexed: 12/19/2022]
Abstract
Our aim was to analyze the prevalence of high-risk human papillomavirus (HR-HPV) and its association with risk factors related to cervical lesions. We used 362 cervical samples from a transversal study to detect nineteen types from the high-risk HPV clade by highly sensitive PCR. Unexpectedly, we found a very high prevalence of HPV type 66 (32.8%), particularly in low-grade squamous intraepithelial lesions. A significant association of HPV66 with previously sexually transmitted disease was observed (p < 0.05). Our results strongly suggest that HPV66 might be indicative of cervical lesions that will not progress to cancer. HPV genotyping by methods that grouped type 66 with other HR-HPV clade types should be interpreted with caution.
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Asthana S, Busa V, Labani S. Oral contraceptives use and risk of cervical cancer-A systematic review & meta-analysis. Eur J Obstet Gynecol Reprod Biol 2020; 247:163-175. [PMID: 32114321 DOI: 10.1016/j.ejogrb.2020.02.014] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 02/03/2020] [Accepted: 02/13/2020] [Indexed: 10/25/2022]
Abstract
BACKGROUND Role of Oral Contraceptive (OC) as a risk factor for cervical cancer remained controversial and unclear. OBJECTIVE To evaluate risk of cervical cancer in OC users and non-users through a comprehensive systematic review. SEARCH STRATEGY Literature search conducted in databases from January 1990 till August 2019 using various search terms. SELECTION CRITERIA Primary research studies that evaluated and assessed the association of OC use with cervical cancer with study design of case control or cohort types published in English language. DATA COLLECTION AND ANALYSIS PRISMA guided review was done by two independent researchers. Effect size estimated by pooled Odds ratio with 95 % Confidence Interval (CI) in random effect models on OC pill use for the risk of cervical cancer. RESULTS Review included 19 studies. Overall risk of invasive cancer on OC use was found to be significant with unknown status of HPV OR (95 % CI) as 1.51 (1.35, 1.68) and for unknown HPV as 1.66 (1.24, 2.21). Adenocarcinoma, squamous cell carcinoma and carcinoma in situ had significant association with OR (95 % CI) of 1.77 (1.4, 2.24), 1.29 (1.18, 1.42) and 1.7 (1.18, 2.44) respectively. CONCLUSION OC pills use had a definite associated risk for developing cervical cancer specially for Adenocarcinoma and longer duration of OC pills use.
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Affiliation(s)
- Smita Asthana
- Scientist E, Division of Epidemiology and Biostatistics, National Institute of Cancer Prevention and Research, Indian Council of Medical Research, India
| | - Vishal Busa
- Scientist E, Division of Epidemiology and Biostatistics, National Institute of Cancer Prevention and Research, Indian Council of Medical Research, India
| | - Satyanarayana Labani
- Scientist E, Division of Epidemiology and Biostatistics, National Institute of Cancer Prevention and Research, Indian Council of Medical Research, India.
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Combined Effect of Secondhand Smoking and Alcohol Drinking on Risk of Persistent Human Papillomavirus Infection. BIOMED RESEARCH INTERNATIONAL 2019; 2019:5829676. [PMID: 31016192 PMCID: PMC6448343 DOI: 10.1155/2019/5829676] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Revised: 01/28/2019] [Accepted: 02/13/2019] [Indexed: 11/17/2022]
Abstract
Tobacco smoking is established as a cofactor of human papillomavirus (HPV) for cervical cancer risk. However, the role of secondhand smoking in cervical carcinogenesis is controversial. We aimed to assess the association between secondhand smoking and high risk- (HR-) HPV persistence, a pivotal event in development of cervical cancer. In total, 9,846 women who underwent health-screening examinations from 2002 to 2011 at the National Cancer Center, Korea, were included. Secondhand smoking was defined as being exposed to secondhand smoke at home or in the workplace. Multivariate logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (CIs) for risks of HR-HPV infection at baseline (N, 9,846, negative vs. positive), 1-year persistence (n, 1,237, 1-year negative vs. 1-year persistence), and 2-year persistence (n, 481, 2-year negative vs. 2-year persistence). Active smoking, secondhand smoking, and secondhand smoking in nonactive smokers had no association with these risks. Among alcohol drinkers, secondhand smoking in nonactive smokers had higher risks of HR-HPV infection at baseline (OR = 1.25, 95% CI = 1.05-1.48, p for multiplicative interaction = 0.003), 1-year persistence (1.75, 1.14-2.68, 0.004), and 2-year persistence (2.96, 1.42-6.15, 0.006), when compared to HR-HPV negative, 1-year negative, and 2-year negative categories, respectively. However, among nonalcohol drinkers, there was no association between smoking or secondhand smoking status and these risks. These findings suggest that women exposed to secondhand smoking at home or in the workplace might be at high risk of HR-HPV persistence when it is combined with alcohol drinking, even though neither active smoking nor secondhand smoking independently affects the risk.
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Risk factors associated with precancerous cervical lesion among women screened at Marie Stops Ethiopia, Adama town, Ethiopia 2017: a case control study. BMC Res Notes 2018; 11:145. [PMID: 29463299 PMCID: PMC5819704 DOI: 10.1186/s13104-018-3244-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2017] [Accepted: 02/10/2018] [Indexed: 01/26/2023] Open
Abstract
OBJECTIVE Although cervical cancer is a preventable disease, it remains a leading cause of death among women in developing countries. In this unmatched case control design, 55 cases and 109 controls were included. The main objective of this study was to assess the risk factors of precancerous cervical lesion in Adama town. RESULTS A total of 164 participants were recruited in this study. Of the 109 controls, 64 (61%) and 41 (39%) of cases were using oral contraception. Women who were using oral contraception were two times at risk for developing precancerous cervical lesion than who were not using (COR = 2.059 95% CI 1.006, 4.216; AOR = 2.342). Out of 55 cases, 21 (38.2%) cases had a history STI and out of 109 controls, 24 (22.2%) controls had a history of STI. It was revealed that STI has a significant association for developing of precancerous lesion. Women who had a history of STI were two times at risk of developing precancerous cervical lesion than who had no (COR = 2.187; AOR = 2.485). It was found that initiation of sexual intercourse before the age of 15 years has 5.6 risks to develop precancerous cervical lesion (COR = 5.625 AOR = 6.703).
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Fernandes K, Chicco D, Cardoso JS, Fernandes J. Supervised deep learning embeddings for the prediction of cervical cancer diagnosis. PeerJ Comput Sci 2018; 4:e154. [PMID: 33816808 PMCID: PMC7924508 DOI: 10.7717/peerj-cs.154] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2018] [Accepted: 04/26/2018] [Indexed: 05/12/2023]
Abstract
Cervical cancer remains a significant cause of mortality all around the world, even if it can be prevented and cured by removing affected tissues in early stages. Providing universal and efficient access to cervical screening programs is a challenge that requires identifying vulnerable individuals in the population, among other steps. In this work, we present a computationally automated strategy for predicting the outcome of the patient biopsy, given risk patterns from individual medical records. We propose a machine learning technique that allows a joint and fully supervised optimization of dimensionality reduction and classification models. We also build a model able to highlight relevant properties in the low dimensional space, to ease the classification of patients. We instantiated the proposed approach with deep learning architectures, and achieved accurate prediction results (top area under the curve AUC = 0.6875) which outperform previously developed methods, such as denoising autoencoders. Additionally, we explored some clinical findings from the embedding spaces, and we validated them through the medical literature, making them reliable for physicians and biomedical researchers.
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Affiliation(s)
- Kelwin Fernandes
- Instituto de Engenharia de Sistemas e Computadores Tecnologia e Ciencia (INESC TEC), Porto, Portugal
- Universidade do Porto, Porto, Portugal
| | - Davide Chicco
- Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Jaime S. Cardoso
- Instituto de Engenharia de Sistemas e Computadores Tecnologia e Ciencia (INESC TEC), Porto, Portugal
- Universidade do Porto, Porto, Portugal
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Okunade KS, Nwogu CM, Oluwole AA, Anorlu RI. Prevalence and risk factors for genital high-risk human papillomavirus infection among women attending the out-patient clinics of a university teaching hospital in Lagos, Nigeria. Pan Afr Med J 2017; 28:227. [PMID: 29629013 PMCID: PMC5882206 DOI: 10.11604/pamj.2017.28.227.13979] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Accepted: 12/12/2017] [Indexed: 11/18/2022] Open
Abstract
Introduction Cervical cancer is the second most common cancer among women in the developing countries and the seventh commonest cancer in the developed countries. Human papillomavirus (HPV) is now known to be the main factor in the aetiology of cervical cancer with over 99.7% of cases being associated with previous high risk HPV (hrHPV) infection. This study was aimed to determine the prevalence and risk factors for genital hrHPV infection among women attending the out-patient clinics of the Lagos University Teaching Hospital. Methods This was a cross-sectional study involving a total of 200 women. Questionnaires were administered to collect data such as sociodemographic, reproductive and sexual histories. Endocervical swab samples were then taken from each participant. Samples were analyzed by polymerase chain reaction (PCR) using consensus primers targeted against the hrHPV viruses. Results The prevalence of hrHPV in the study was 36.5%. The most predominant HPV subtypes were 31 (25.0%), 35 (8.0%) and 16 (3.5%) with the largest proportion (76.1%) of the tested samples being positive for only a single hrHPV subtype. The study showed statistically significant associations between early age at coitarche (P = 0.032) and increasing number of lifetime sexual partners (P = 0.001) with genital hrHPV infection. Conclusion The prevalence of hrHPV was high in Lagos with the majority of test positive samples having only a single HPV genotype. We demonstrated early age of sexual debut and increasing number of lifetime sexual partners as the most important factors associated with genital hrHPV infection.
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Affiliation(s)
- Kehinde Sharafadeen Okunade
- Department of Obstetrics & Gynaecology, Lagos University Teaching Hospital Lagos, Nigeria.,Department of Obstetrics & Gynaecology, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Chidinma Magnus Nwogu
- Department of Obstetrics & Gynaecology, Lagos University Teaching Hospital Lagos, Nigeria
| | - Ayodeji Ayotunde Oluwole
- Department of Obstetrics & Gynaecology, Lagos University Teaching Hospital Lagos, Nigeria.,Department of Obstetrics & Gynaecology, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Rose Ihuoma Anorlu
- Department of Obstetrics & Gynaecology, Lagos University Teaching Hospital Lagos, Nigeria.,Department of Obstetrics & Gynaecology, College of Medicine, University of Lagos, Lagos, Nigeria
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Bassal R, Schejter E, Bachar R, Perri T, Korach J, Jakobson-Setton A, Ben-David LH, Cohen D, Keinan-Boker L. Risk Factors for Cervical Cancer and CIN3 in Jewish Women in Israel - Two Case Control Studies. Asian Pac J Cancer Prev 2017; 17:2067-73. [PMID: 27221897 DOI: 10.7314/apjcp.2016.17.4.2067] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
PURPOSE The aim of the study was to identify risk and protective factors/markers for cervical cancer and cervical intraepithelial neoplasia 3 (CIN3) in Israeli Jewish women in order to settle the discrepancy of low incidence rate of cervical cancer and relatively high incidence rate of CIN3. MATERIALS AND METHODS We conducted two case control studies, which examined the association between potential risk and protective factors/markers for cervical cancer or CIN3 using self administered detailed questionnaires. RESULTS For studying cervical cancer, 40 cases and 40 matched controls were interviewed. In the univariable and multivariable analyses older age, depression or anxiety and ever smoking seemed to act as independent risk factors/markers, while older age at first intercourse was protective. For studying CIN3, 99 cases and 79 controls were interviewed. Multivariable analysis has demonstrated that being born in Israel, depression or anxiety and ever smoking were independent risk factors/markers for CIN3. CONCLUSIONS The risk factors/markers studied, that were associated with cervical cancer or CIN3 among Jewish women in Israel, are similar to those reported in other parts of the world, and do not explain the observed discrepancy of high in-situ cervical cancer rates and low invasive cervical cancer incidence in Israel.
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Affiliation(s)
- Ravit Bassal
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Israel E-mail :
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Muwonge R, Ngo Mbus L, Ngoma T, Gombe Mbalawa C, Dolo A, da Ganda Manuel M, Nouhou H, Nacoulma M, Mwaiselage J, Koulibaly M, Bayo S, Nsonde Malanda J, De Vuyst H, Herrero R, Sankaranarayanan R, Keita N. Socio-demographic and reproductive determinants of cervical neoplasia in seven sub-Sahara African countries. Cancer Causes Control 2016; 27:1437-1446. [PMID: 27822586 DOI: 10.1007/s10552-016-0823-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Accepted: 10/25/2016] [Indexed: 11/29/2022]
Abstract
BACKGROUND Since most human papilloma virus (HPV) infections regress without any intervention, HPV is a necessary but may not be a solely sufficient cause of cervical intraepithelial neoplasia (CIN) and cervical cancer. Hence, the influence of cofactors on progression from cervical HPV infection to high-grade CIN and invasive cervical cancer has been a subject of intensive research. OBJECTIVE We assessed the effect of socio-demographic and sexual reproductive factors on the prevalence of invasive cervical cancer and CIN diagnosed in cross-sectional cervical cancer screening projects carried out in seven sites of different sub-Saharan countries. METHODS Between January 2000 and August 2007, healthy women aged 25-59 who participated in the screening projects were interviewed for socio-demographic, reproductive, and behavioral characteristics, investigated for disease confirmation with colposcopy, and had biopsies directed from colposcopically abnormal areas by trained local physicians. Odds ratios (ORs) and their 95% confidence intervals (CIs) from logistic regression analyses were used to assess the effect of women characteristics on CIN 1, CIN 2-3, CIN 3, and invasive cancer outcome measures. RESULTS Among 47,361 women screened and investigated for disease confirmation, CIN 1 was diagnosed in 1,069 (2.3%), CIN 2 in 517 (1.1%), CIN 3 in 175 (0.5%), and invasive cancer in 485 (1.0%). The site-specific prevalence of CIN 2-3 lesions ranged from 0.3 to 5.1% and from 0.2 to 1.9% for invasive cancers. Risk factors for CIN 2-3 were being widowed or separated versus currently married (OR 1.3, 95% CI 1.0-1.7 a); and having had at least four pregnancies versus zero or one pregnancy (OR at least 1.4-fold, 95% CI 1.1-1.8). Risk factors for invasive cancer were being widowed or separated versus currently married (OR 2.0, 95% CI 1.3-3.1); and having had at least three pregnancies versus zero or one pregnancy (OR at least 3.0-fold, 95% CI 2.1-4.2). Additionally, cervical cancer risk increased with increasing age, age at menarche, and age at marriage, while the risk decreased with increasing level of education and in those with some form of employment compared to housewives. CONCLUSION The exposure of the exocervix and/or the increased levels of estrogen and progesterone for more prolonged periods during pregnancy in multiparous women and the vulnerability of widowed/separated women in society might result in increased risk of cervical neoplasia more so among women exposed to HPV infection. High parity probably explains the persistently high rates of cervical cancer in sub-Saharan Africa.
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Affiliation(s)
- Richard Muwonge
- Screening Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372, Lyon Cedex 08, France.
| | - Louise Ngo Mbus
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, France
| | - Twalib Ngoma
- Ocean Road Cancer Institute, Dar es Salaam, United Republic of Tanzania
| | | | - Amadou Dolo
- Département de Gynécologie-Obstétrique, Hôpital Gabriel Touré, Bamako, Mali
| | | | - Hassan Nouhou
- Faculté des Sciences de la Santé, Université de Niamey, Niamey, Niger
| | - Marius Nacoulma
- Département de Gynécologie-Obstétrique, Centre Hospitalier National Yalgado Ouédraogo, Ouagadougou, Burkina Faso
| | - Julius Mwaiselage
- Ocean Road Cancer Institute, Dar es Salaam, United Republic of Tanzania
| | - Moussa Koulibaly
- Centre National d'Anatomie Pathologique, CHU Donka, Conakry, Guinea
| | | | | | - Hugo De Vuyst
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, France
| | - Rolando Herrero
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, France
| | - Rengaswamy Sankaranarayanan
- Screening Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372, Lyon Cedex 08, France
| | - Namory Keita
- Service de Gynécologie/Obstétrique, CHU Donka, Conakry, Guinea
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Guthrie S, Bienkowska-Gibbs T, Manville C, Pollitt A, Kirtley A, Wooding S. The impact of the National Institute for Health Research Health Technology Assessment programme, 2003-13: a multimethod evaluation. Health Technol Assess 2016; 19:1-291. [PMID: 26307643 DOI: 10.3310/hta19670] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme supports research tailored to the needs of NHS decision-makers, patients and clinicians. This study reviewed the impact of the programme, from 2003 to 2013, on health, clinical practice, health policy, the economy and academia. It also considered how HTA could maintain and increase its impact. METHODS Interviews (n = 20): senior stakeholders from academia, policy-making organisations and the HTA programme. Bibliometric analysis: citation analysis of publications arising from HTA programme-funded research. Researchfish survey: electronic survey of all HTA grant holders. Payback case studies (n = 12): in-depth case studies of HTA programme-funded research. RESULTS We make the following observations about the impact, and routes to impact, of the HTA programme: it has had an impact on patients, primarily through changes in guidelines, but also directly (e.g. changing clinical practice); it has had an impact on UK health policy, through providing high-quality scientific evidence - its close relationships with the National Institute for Health and Care Excellence (NICE) and the National Screening Committee (NSC) contributed to the observed impact on health policy, although in some instances other organisations may better facilitate impact; HTA research is used outside the UK by other HTA organisations and systematic reviewers - the programme has an impact on HTA practice internationally as a leader in HTA research methods and the funding of HTA research; the work of the programme is of high academic quality - the Health Technology Assessment journal ensures that the vast majority of HTA programme-funded research is published in full, while the HTA programme still encourages publication in other peer-reviewed journals; academics agree that the programme has played an important role in building and retaining HTA research capacity in the UK; the HTA programme has played a role in increasing the focus on effectiveness and cost-effectiveness in medicine - it has also contributed to increasingly positive attitudes towards HTA research both within the research community and the NHS; and the HTA focuses resources on research that is of value to patients and the UK NHS, which would not otherwise be funded (e.g. where there is no commercial incentive to undertake research). The programme should consider the following to maintain and increase its impact: providing targeted support for dissemination, focusing resources when important results are unlikely to be implemented by other stakeholders, particularly when findings challenge vested interests; maintaining close relationships with NICE and the NSC, but also considering other potential users of HTA research; maintaining flexibility and good relationships with researchers, giving particular consideration to the Technology Assessment Report (TAR) programme and the potential for learning between TAR centres; maintaining the academic quality of the work and the focus on NHS need; considering funding research on the short-term costs of the implementation of new health technologies; improving the monitoring and evaluation of whether or not patient and public involvement influences research; improve the transparency of the priority-setting process; and continuing to monitor the impact and value of the programme to inform its future scientific and administrative development.
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Prognostic factors in neuroendocrine cervical carcinoma. Obstet Gynecol Sci 2016; 59:116-22. [PMID: 27004202 PMCID: PMC4796081 DOI: 10.5468/ogs.2016.59.2.116] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2015] [Revised: 09/30/2015] [Accepted: 10/21/2015] [Indexed: 11/08/2022] Open
Abstract
Objective To evaluate the clinical and pathologic factors associated with survival in patients with neuroendocrine cervical carcinoma (NECC). Methods The records of 61 patients with NECC diagnosed between 2000 and 2014 at Seoul National University Hospital and the National Cancer Center were retrospectively reviewed. Kaplan-Meier and Cox regression methods were used for analyses. Results Of the 61 patients, 67.2% were diagnosed at early stage (I to IIA) with a median age of 49 years. Of those, 78% underwent surgery and 75.6% received postoperative adjuvant treatment. For patients diagnosed at advanced stage, 60.0% received chemotherapy only and 25.0% received concurrent chemoradiation therapy. In the univariate analysis, advanced stage (77 vs. 40 months, P=0.013), tumor size ≥2 cm (133 vs. 47 months, P=0.002) and mixed tumor (101 vs. 34 months, P=0.004) were shown to be poor prognostic factors. In the multivariate analysis, tumor stage, tumor size and tumor homology were shown to be independent prognostic factors for overall survival. Of the total, 39.3% of the patients experienced recurrence, and 54.1% of the patients had metastasis. Of the patients diagnosed at early stage, 51.2% experienced recurrence. Conclusion Tumor stage, tumor size and tumor homology were found to be independent prognostic factors in patients with NECC. Even in patients diagnosed at early stage, recurrence and distant metastasis were frequently observed.
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Chen Wongworawat Y, Filippova M, Williams VM, Filippov V, Duerksen-Hughes PJ. Chronic oxidative stress increases the integration frequency of foreign DNA and human papillomavirus 16 in human keratinocytes. Am J Cancer Res 2016; 6:764-80. [PMID: 27186429 PMCID: PMC4859882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 02/03/2016] [Indexed: 06/05/2023] Open
Abstract
Cervical cancer is the second most common cancer, and the fourth most common cause of cancer death in women worldwide. Nearly all of these cases are caused by high-risk HPVs (HR HPVs), of which HPV16 is the most prevalent type. In most cervical cancer specimens, HR HPVs are found integrated into the human genome, indicating that integration is a key event in cervical tumor development. An understanding of the mechanisms that promote integration may therefore represent a unique opportunity to intercept carcinogenesis. To begin identifying these mechanisms, we tested the hypothesis that chronic oxidative stress (OS) induced by virus- and environmentallymediated factors can induce DNA damage, and thereby increase the frequency with which HPV integrates into the host genome. We found that virus-mediated factors are likely involved, as expression of E6*, a splice isoform of HPV16 E6, increased the levels of reactive oxygen species (ROS), caused oxidative DNA damage, and increased the frequency of plasmid DNA integration as assessed by colony formation assays. To assess the influence of environmentally induced chronic OS, we used L-Buthionine-sulfoximine (BSO) to lower the level of the intracellular antioxidant glutathione. Similar to our observations with E6*, glutathione depletion by BSO also increased ROS levels, caused oxidative DNA damage and increased the integration frequency of plasmid DNA. Finally, under conditions of chronic OS, we were able to induce and characterize a few independent events in which episomal HPV16 integrated into the host genome of cervical keratinocytes. Our results support a chain of events leading from induction of oxidative stress, to DNA damage, to viral integration, and ultimately to carcinogenesis.
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Affiliation(s)
- Yan Chen Wongworawat
- Department of Basic Science, Loma Linda University School of Medicine Loma Linda, CA, USA
| | - Maria Filippova
- Department of Basic Science, Loma Linda University School of Medicine Loma Linda, CA, USA
| | - Vonetta M Williams
- Department of Basic Science, Loma Linda University School of Medicine Loma Linda, CA, USA
| | - Valery Filippov
- Department of Basic Science, Loma Linda University School of Medicine Loma Linda, CA, USA
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Roura E, Travier N, Waterboer T, de Sanjosé S, Bosch FX, Pawlita M, Pala V, Weiderpass E, Margall N, Dillner J, Gram IT, Tjønneland A, Munk C, Palli D, Khaw KT, Overvad K, Clavel-Chapelon F, Mesrine S, Fournier A, Fortner RT, Ose J, Steffen A, Trichopoulou A, Lagiou P, Orfanos P, Masala G, Tumino R, Sacerdote C, Polidoro S, Mattiello A, Lund E, Peeters PH, Bueno-de-Mesquita HB, Quirós JR, Sánchez MJ, Navarro C, Barricarte A, Larrañaga N, Ekström J, Lindquist D, Idahl A, Travis RC, Merritt MA, Gunter MJ, Rinaldi S, Tommasino M, Franceschi S, Riboli E, Castellsagué X. The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort. PLoS One 2016; 11:e0147029. [PMID: 26808155 PMCID: PMC4726518 DOI: 10.1371/journal.pone.0147029] [Citation(s) in RCA: 83] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Accepted: 12/27/2015] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). METHODS AND FINDINGS We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥ 15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). CONCLUSIONS Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.
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Affiliation(s)
- Esther Roura
- Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Noémie Travier
- Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain
| | - Tim Waterboer
- Division of Molecular Diagnostics of Oncogenic Infections (F020), Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Silvia de Sanjosé
- Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - F. Xavier Bosch
- Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain
| | - Michael Pawlita
- Division of Molecular Diagnostics of Oncogenic Infections (F020), Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Valeria Pala
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Elisabete Weiderpass
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
- Department of Research, Cancer Registry of Norway, Oslo, Norway
- Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland
| | - Núria Margall
- Microbiology Department, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain
| | - Joakim Dillner
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Inger T. Gram
- Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
| | - Anne Tjønneland
- Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Christian Munk
- Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Domenico Palli
- Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute–ISPO, Florence, Italy
| | - Kay-Tee Khaw
- School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Kim Overvad
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Françoise Clavel-Chapelon
- Inserm, Centre for research in Epidemiology and Population Health (CESP), U318, Nutrition, Hormones and Women’s Health team, F-94705, Villejuif, France
- Université Paris Sud, UMRS 318, F-94705, Villejuif, France
- Institut Gustave Roussy, F-94705, Villejuif, France
| | - Sylvie Mesrine
- Inserm, Centre for research in Epidemiology and Population Health (CESP), U318, Nutrition, Hormones and Women’s Health team, F-94705, Villejuif, France
- Université Paris Sud, UMRS 318, F-94705, Villejuif, France
- Institut Gustave Roussy, F-94705, Villejuif, France
| | - Agnès Fournier
- Inserm, Centre for research in Epidemiology and Population Health (CESP), U318, Nutrition, Hormones and Women’s Health team, F-94705, Villejuif, France
- Université Paris Sud, UMRS 318, F-94705, Villejuif, France
- Institut Gustave Roussy, F-94705, Villejuif, France
| | - Renée T. Fortner
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jennifer Ose
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Annika Steffen
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | | | - Pagona Lagiou
- Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece
- Department of Epidemiology, Harvard School of Public Health, Boston, United States of America
| | - Philippos Orfanos
- Hellenic Health Foundation, Athens, Greece
- Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece
| | - Giovanna Masala
- Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute–ISPO, Florence, Italy
| | - Rosario Tumino
- Cancer Registry and Histopathology Unit, "Civic—M.P. Arezzo" Hospital, Ragusa, Italy
| | - Carlotta Sacerdote
- Unit of Cancer Epidemiology, University of Turin, Turin, Italy
- Centre for Cancer Epidemiology and Prevention (CPO Piemonte), Turin, Italy
| | | | - Amalia Mattiello
- Dipartimento Di Medicina Clinica E Chirurgia, Federico II University, Naples, Italy
| | - Eiliv Lund
- Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
| | - Petra H. Peeters
- MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - H. B(as). Bueno-de-Mesquita
- Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
- Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom
- Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | | | - María-José Sánchez
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
| | - Carmen Navarro
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain
- Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain
| | - Aurelio Barricarte
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Navarra Public Health Institute, Pamplona, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
| | - Nerea Larrañaga
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Public Health Division of Gipuzkoa, BIODonostia Research Institute, Basque Health Department, Bilbao, Spain
| | - Johanna Ekström
- BBMRI.se Service Center for Southern Sweden, Lund University, Medicon Village, Lund, Sweden
| | - David Lindquist
- Department of Radiation Sciences, Umeå University, Umeå, Sweden
| | - Annika Idahl
- Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden
| | - Ruth C. Travis
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Melissa A. Merritt
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom
| | - Marc J. Gunter
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom
| | - Sabina Rinaldi
- International Agency for Research on Cancer, Lyon, France
| | | | | | - Elio Riboli
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom
| | - Xavier Castellsagué
- Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
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Labeit A, Peinemann F. Breast and cervical cancer screening in Great Britain: Dynamic interrelated processes. HEALTH ECONOMICS REVIEW 2015; 5:32. [PMID: 26487452 PMCID: PMC4615931 DOI: 10.1186/s13561-015-0065-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Accepted: 10/07/2015] [Indexed: 06/05/2023]
Abstract
No previous analysis has investigated the determinants of screening uptake for breast and cervical cancer screening for possible spillover effects from one type of screening examination to the other type of screening examination with a dynamic bivariate panel probit model. For our analysis, we used a dynamic random effects bivariate panel probit model with initial conditions (Wooldridge-type estimator) and dependent variables were the participation of breast and cervical cancer screening in the recent year. The balanced panel sample consisted of 844 women from the British Household Panel Survey (BHPS) from the time period 1992 to 2008. Our analysis showed the high relevance of past screening behaviour and the importance of state dependency for the same and the other type of cancer screening examinations even after controlling for covariates and unobserved heterogeneity. The uptake for breast and cervical cancer screening was higher when the same screening examination was done one or three years earlier. This result is in accordance with the medical screening programmes in Great Britain. With regard to breast and cervical cancer screening positive spillover effects existed between screening examinations in the third order lags. Women with a previous visit to a general practitioner and individuals in the recommended age groups had a higher uptake for breast and cervical cancer screening. Other socioeconomic and health related variables had non-uniform results in both screening examinations. Promoting the uptake of one female prevention activity could also enhance the uptake of the other prevention activity.
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Affiliation(s)
- Alexander Labeit
- School of Health and Related Sciences, Regent Court, University of Sheffield, 30 Regent Street, Sheffield, S1 4DA, UK.
| | - Frank Peinemann
- FOM University of Applied Science for Economics & Management, Leimkugelstr. 6, 45141, Essen, Germany.
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Prevalence of human papillomavirus infection in Guangdong Province, China: a population-based survey of 78,355 women. Sex Transm Dis 2015; 41:732-8. [PMID: 25581810 DOI: 10.1097/olq.0000000000000201] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The prevalence of human papillomavirus (HPV) infection and the distribution of different HPV genotypes vary greatly within different geographical and ethnic populations, especially in Asia. The HPV infection data based on regional population are extremely important for researchers to develop new efficient HPV screening assays and estimate the effect of vaccines on preventing from cervical cancer. METHODS A total of 78,355 women from Guangdong Province, China, whose ages were from 18 to 75 years were enrolled in this study. All epidemiological data were obtained by face-to-face interview. Cervical exfoliated cells were collected, and HPV-DNA test was conducted with the matrix-assisted laser desorption/ionization time-of flight mass spectrometry. RESULTS The overall HPV infection prevalence in the study population was 7.3%. The top 6 HPV genotypes were HPV16 (1.5%), HPV52 (1.2%), HPV58 (1.0%), HPV18 (0.7%), HPV45 (0.5%), and HPV6 (0.5%), accounting for 69.7% of all detected HPV infection types. Two peaks of HPV infection were detected in the population of old age group (>50; 9.6%) and young group (<25; 8.2%). Infection with single genotype HPV (6.2% in all; 85.7% in HPV-positive women) was more frequent than infection with multiple HPV (1.0% and 14.3% respectively). Results of multivariate logistic regression revealed that sexual active years, numbers of sexual partner, and numbers of pregnancy were risk factors of HPV infection. CONCLUSIONS This study provides useful epidemiological information on cervical HPV infection prevalence in general female population from Guangdong Province, China. In this population, HPV infection prevalence was 7.3%, and genotypes HPV16, HPV52, and HPV58 showed a relatively high prevalence.
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Makuza JD, Nsanzimana S, Muhimpundu MA, Pace LE, Ntaganira J, Riedel DJ. Prevalence and risk factors for cervical cancer and pre-cancerous lesions in Rwanda. Pan Afr Med J 2015; 22:26. [PMID: 26664527 PMCID: PMC4662515 DOI: 10.11604/pamj.2015.22.26.7116] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 09/02/2015] [Indexed: 01/28/2023] Open
Abstract
INTRODUCTION Cervical cancer prevalence in Rwanda has not been well-described. Visual inspection with acetic acid or Lugol solution has been shown to be effective for cervical cancer screening in low resource settings. The aim of the study is to understand the prevalence and risk factors for cervical cancer and pre- cancerous lesions among Rwandan women between 30 and 50 old undergoing screening. METHODS This cross-sectional analytical study was done in 3 districts of Rwanda from October 2010 to June 2013. Women aged 30 to 50 years screened for cervical cancer by trained doctors, nurses and midwives. Prevalence of pre-cancerous and cancerous cervical lesions was determined. Bivariate and multivariate logistic regressions were used to assess risk factors associated with cervical cancer. RESULTS The prevalence of pre-cancer and invasive cervical cancer was 5.9% (95% CI 4.5, 7.5) and 1.7% (95% CI 0.9, 2.5), respectively. Risk factors associated with cervical cancer in multivariate analysis included initiation of sexual activity at less than 20 years (OR=1.75; 95% CI=(1.01, 3.03); being unmarried (single, divorced and widowed) (OR=3.29; 95% CI=( 1.26, 8.60)); Older age of participants (OR= 0.52; 95% CI= (0.28, 0.97)), older age at the first pregnancy (OR=2.10; 95% CI=(1.20, 3.67) and higher number of children born (OR=0.42; 95%CI =(0.23, 0.76)) were protective. CONCLUSION Cervical cancer continues to be a public health problem in Rwanda, but screening using VIA is practical and feasible even in rural settings.
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Affiliation(s)
| | | | | | | | - Joseph Ntaganira
- University of Rwanda, College of Medicine and Other Health Sciences, School of Public Health, Rwanda
| | - David James Riedel
- Institute of Human Virology and Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, Maryland, USA
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Mongelos P, Mendoza LP, Rodriguez-Riveros I, Castro A, Gimenez G, Araujo P, Paez M, Castro W, Basiletti J, González J, Echagüe G, Diaz V, Laspina F, Ever S, Marecos R, Deluca G, Picconi MA. Distribution of human papillomavirus (HPV) genotypes and bacterial vaginosis presence in cervical samples from Paraguayan indigenous. Int J Infect Dis 2015; 39:44-9. [PMID: 26283550 DOI: 10.1016/j.ijid.2015.08.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 07/29/2015] [Accepted: 08/07/2015] [Indexed: 10/23/2022] Open
Abstract
OBJECTIVE To determine the frequency of human papillomavirus (HPV) types and to assess bacterial vaginosis (BV) possible associations with cervical infections in indigenous Paraguayan women of the Department of Presidente Hayes. METHODS This study included 181 sexually active women without cervical lesions. HPV typing was performed by polymerase chain reaction with primers PGMY 09/11 followed by reverse line hybridization. BV was diagnosed by the Nugent criteria using the results from a Gram stain smear. RESULTS Sixteen percent of women were positive for at least one high risk HPV type (HR-HPV). The most frequent genotypes were HPV 16 (4.4%), followed by HPV 58 (3.3%), HPV 45 (3.3%), HPV 53 (2.8%) and HPV 11 (2.8%). A significant association between HR-HPV and BV was observed (p=0.01). In addition, women with BV had a higher frequency of Chlamydia trachomatis (p=0.0007), Trichomonas vaginalis (p=0.00009), Mycoplasma hominis (p=0.001). CONCLUSIONS A large variety of HPV genotypes was detected and showed a slightly different pattern from previous studies on urban women in Paraguay, with the predominance of HR-HPV. Furthermore, the information of co-infections involved in BV could be useful for the improvement of national prevention programs, as well as for laboratory surveillance of these genital infections.
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Affiliation(s)
- Pamela Mongelos
- Department of Public Health, Health Sciences Research Institute (IICS), National University of Asuncion (UNA), Paraguay.
| | - Laura Patricia Mendoza
- Department of Public Health, Health Sciences Research Institute (IICS), National University of Asuncion (UNA), Paraguay.
| | - Isabel Rodriguez-Riveros
- Department of Public Health, Health Sciences Research Institute (IICS), National University of Asuncion (UNA), Paraguay.
| | - Amalia Castro
- Department of Public Health, Health Sciences Research Institute (IICS), National University of Asuncion (UNA), Paraguay.
| | - Graciela Gimenez
- Department of Public Health, Health Sciences Research Institute (IICS), National University of Asuncion (UNA), Paraguay.
| | - Patricia Araujo
- Department of Public Health, Health Sciences Research Institute (IICS), National University of Asuncion (UNA), Paraguay.
| | - Malvina Paez
- Department of Public Health, Health Sciences Research Institute (IICS), National University of Asuncion (UNA), Paraguay.
| | - Wilberto Castro
- Cervical Pathology Department, Faculty of Medical Sciences, UNA, Paraguay.
| | - Jorge Basiletti
- Oncogenic Virus Service, National Institute of Infectious Diseases (INEI) - ANLIS "Dr. Malbrán", Buenos Aires, Argentina.
| | - Joaquín González
- Oncogenic Virus Service, National Institute of Infectious Diseases (INEI) - ANLIS "Dr. Malbrán", Buenos Aires, Argentina.
| | - Gloria Echagüe
- Department of Clinical and microbiological analysis, IICS, UNA, Paraguay.
| | - Valentina Diaz
- Department of Clinical and microbiological analysis, IICS, UNA, Paraguay.
| | - Florentina Laspina
- Department of Clinical and microbiological analysis, IICS, UNA, Paraguay.
| | - Santiago Ever
- Regional Hospital of Villa Hayes, Ministry of Public Health, Department of President Hayes, Paraguay.
| | - Ramón Marecos
- Health Center of Pozo Colorado, Ministry of Public Health, Department of Presidente Hayes, Paraguay.
| | - Gerardo Deluca
- Molecular Applications Laboratory, Faculty of Medicine, Northeast National University, Corrientes, Argentina.
| | - María Alejandra Picconi
- Oncogenic Virus Service, National Institute of Infectious Diseases (INEI) - ANLIS "Dr. Malbrán", Buenos Aires, Argentina.
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Han KT, Kim SJ, Lee SY, Park EC. Cost-effectiveness analysis of HPV vaccination: comparing the general population with socially vulnerable individuals. Asian Pac J Cancer Prev 2015; 15:8503-8. [PMID: 25339055 DOI: 10.7314/apjcp.2014.15.19.8503] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND After the WHO recommended HPV vaccination of the general population in 2009, government support of HPV vaccination programs was increased in many countries. However, this policy was not implemented in Korea due to perceived low cost-effectiveness. Thus, the aim of this study was to analyze the cost-utility of HPV vaccination programs targeted to high risk populations as compared to vaccination programs for the general population. MATERIALS AND METHODS Each study population was set to 100,000 people in a simulation study to determine the incremental cost-utility ratio (ICUR), then standard prevalence rates, cost, vaccination rates, vaccine efficacy, and the Quality-Adjusted Life-Years (QALYs) were applied to the analysis. In addition, sensitivity analysis was performed by assuming discounted vaccination cost. RESULTS In the socially vulnerable population, QALYs gained through HPV vaccination were higher than that of the general population (General population: 1,019, Socially vulnerable population: 5,582). The results of ICUR showed that the cost of HPV vaccination was higher for the general population than the socially vulnerable population. (General population: 52,279,255 KRW, Socially vulnerable population: 9,547,347 KRW). Compared with 24 million KRW/QALYs as the social threshold, vaccination of the general population was not cost-effective. In contrast, vaccination of the socially vulnerable population was strongly cost-effective. CONCLUSIONS The results suggest the importance and necessity of government support of HPV vaccination programs targeted to socially vulnerable populations because a targeted approach is much more cost-effective. The implementation of government support for such vaccination programs is a critical strategy for decreasing the burden of HPV infection in Korea.
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Affiliation(s)
- Kyu-Tae Han
- Department of Public Health, College of Medicine, Yonsei University, Seoul, Korea E-mail :
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Tavares MCM, de Lima Júnior SF, Coelho AVC, Marques TRNM, de Araújo DHT, Heráclio SDA, Amorim MMR, de Souza PRE, Crovella S. Tumor necrosis factor (TNF) alpha and interleukin (IL) 18 genes polymorphisms are correlated with susceptibility to HPV infection in patients with and without cervical intraepithelial lesion. Ann Hum Biol 2015; 43:261-8. [DOI: 10.3109/03014460.2014.1001436] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
| | | | - Antonio V. C. Coelho
- Department of Genetics, Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil,
| | | | | | | | - Melânia M. Ramos Amorim
- Maternal and Child Healthcare Departament, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, PE, Brazil, and
| | | | - Sergio Crovella
- Department of Genetics, Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil,
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Marks MA, Gupta S, Liaw KL, Tadesse A, Kim E, Phongnarisorn C, Wootipoom V, Yuenyao P, Vipupinyo C, Rugpao S, Sriplienchan S, Gravitt PE, Celentano DD. Prevalence and correlates of HPV among women attending family-planning clinics in Thailand. BMC Infect Dis 2015; 15:159. [PMID: 25887797 PMCID: PMC4387719 DOI: 10.1186/s12879-015-0886-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Accepted: 03/12/2015] [Indexed: 11/12/2022] Open
Abstract
Background Cervical cancer is the most common cancer among women of reproductive age in Thailand. However, information on the prevalence and correlates of anogenital HPV infection in Thailand is sparse. Methods HPV genotype information, reproductive factors, sexual behavior, other STI and clinical information, and cervical cytology and histology were assessed at enrollment among one thousand two hundred and fifty-six (n = 1,256) HIV negative women aged 20–37 from Thailand enrolled in a prospective study of the natural history of HPV. The type-specific prevalence of HPV was estimated using cervical swab specimens from healthy women and women with a diagnosis of CIN 2/3 at baseline. Prevalence ratios (95% CI) were estimated using Poisson regression to quantify the association of demographic, behavioral, and clinical correlates with prevalent HPV infection. Results Overall, 307 (24.6%) and 175 (14.0%) of women were positive for any HPV type and any HR-HPV type, respectively; the most common types were 72, 52, 62, and 16. Among women diagnosed with CIN 2/3 at enrollment (n = 11), the most prevalent HPV types were 52 and 16. In multivariate analysis, HPV prevalence at enrollment was higher among women with: long-term combined oral contraceptive use, a higher number of lifetime sexual partners, a prior Chlamydia infection, and a current diagnosis of Bacterial Vaginosis. Conclusion The study findings provide important information that can be used in the evaluation of primary and secondary interventions designed to reduce the burden of cervical cancer in Thailand. Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-0886-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Morgan A Marks
- Merck Research Laboratories, West Point, PA, USA. .,Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
| | - Swati Gupta
- Merck Research Laboratories, West Point, PA, USA.
| | - Kai-Li Liaw
- Merck Research Laboratories, West Point, PA, USA.
| | | | - Esther Kim
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
| | | | | | | | | | - Sungwal Rugpao
- Research Institute for Health Sciences, Chiang Mai, Thailand.
| | | | - Patti E Gravitt
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
| | - David D Celentano
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
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Borna N, Tabassum S, Jahan M, Munshi S, Unnesa A. Genotyping of High Risk Human Papillomavirus (HPV) among cervical precancer and cancer patients. ACTA MEDICA INTERNATIONAL 2015. [DOI: 10.5530/ami.2015.1.5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Affiliation(s)
- Rebecca MacLeod
- Department of Paediatrics, Hampshire Hospitals NHS Trust, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - Catherine Tuffrey
- Child Health Services, Unit A4 Alpha Court, Segensworth Business Centre, Fareham, UK
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Chen Y, Williams V, Filippova M, Filippov V, Duerksen-Hughes P. Viral carcinogenesis: factors inducing DNA damage and virus integration. Cancers (Basel) 2014; 6:2155-86. [PMID: 25340830 PMCID: PMC4276961 DOI: 10.3390/cancers6042155] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Revised: 10/03/2014] [Accepted: 10/09/2014] [Indexed: 12/13/2022] Open
Abstract
Viruses are the causative agents of 10%-15% of human cancers worldwide. The most common outcome for virus-induced reprogramming is genomic instability, including accumulation of mutations, aberrations and DNA damage. Although each virus has its own specific mechanism for promoting carcinogenesis, the majority of DNA oncogenic viruses encode oncogenes that transform infected cells, frequently by targeting p53 and pRB. In addition, integration of viral DNA into the human genome can also play an important role in promoting tumor development for several viruses, including HBV and HPV. Because viral integration requires the breakage of both the viral and the host DNA, the integration rate is believed to be linked to the levels of DNA damage. DNA damage can be caused by both endogenous and exogenous factors, including inflammation induced by either the virus itself or by co-infections with other agents, environmental agents and other factors. Typically, cancer develops years to decades following the initial infection. A better understanding of virus-mediated carcinogenesis, the networking of pathways involved in transformation and the relevant risk factors, particularly in those cases where tumorigenesis proceeds by way of virus integration, will help to suggest prophylactic and therapeutic strategies to reduce the risk of virus-mediated cancer.
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Affiliation(s)
- Yan Chen
- Department of Basic Science, Loma Linda University, Loma Linda, CA 92354, USA.
| | - Vonetta Williams
- Department of Basic Science, Loma Linda University, Loma Linda, CA 92354, USA.
| | - Maria Filippova
- Department of Basic Science, Loma Linda University, Loma Linda, CA 92354, USA.
| | - Valery Filippov
- Department of Basic Science, Loma Linda University, Loma Linda, CA 92354, USA.
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Guillaud M, Buys TPH, Carraro A, Korbelik J, Follen M, Scheurer M, Storthz KA, van Niekerk D, MacAulay CE. Evaluation of HPV infection and smoking status impacts on cell proliferation in epithelial layers of cervical neoplasia. PLoS One 2014; 9:e107088. [PMID: 25210770 PMCID: PMC4161429 DOI: 10.1371/journal.pone.0107088] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2014] [Accepted: 08/05/2014] [Indexed: 12/14/2022] Open
Abstract
Accurate cervical intra-epithelial neoplasia (CIN) lesion grading is needed for effective patient management. We applied computer-assisted scanning and analytic approaches to immuno-stained CIN lesion sections to more accurately delineate disease states and decipher cell proliferation impacts from HPV and smoking within individual epithelial layers. A patient cohort undergoing cervical screening was identified (n = 196) and biopsies of varying disease grades and with intact basement membranes and epithelial layers were obtained (n = 261). Specimens were sectioned, stained (Mib1), and scanned using a high-resolution imaging system. We achieved semi-automated delineation of proliferation status and epithelial cell layers using Otsu segmentation, manual image review, Voronoi tessellation, and immuno-staining. Data were interrogated against known status for HPV infection, smoking, and disease grade. We observed increased cell proliferation and decreased epithelial thickness with increased disease grade (when analyzing the epithelium at full thickness). Analysis within individual cell layers showed a ≥50% increase in cell proliferation for CIN2 vs. CIN1 lesions in higher epithelial layers (with minimal differences seen in basal/parabasal layers). Higher rates of proliferation for HPV-positive vs. -negative cases were seen in epithelial layers beyond the basal/parabasal layers in normal and CIN1 tissues. Comparing smokers vs. non-smokers, we observed increased cell proliferation in parabasal (low and high grade lesions) and basal layers (high grade only). In sum, we report CIN grade-specific differences in cell proliferation within individual epithelial layers. We also show HPV and smoking impacts on cell layer-specific proliferation. Our findings yield insight into CIN progression biology and demonstrate that rigorous, semi-automated imaging of histopathological specimens may be applied to improve disease grading accuracy.
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Affiliation(s)
- Martial Guillaud
- Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
- * E-mail:
| | - Timon P. H. Buys
- Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
| | - Anita Carraro
- Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
| | - Jagoda Korbelik
- Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
| | - Michele Follen
- Department of Obstetrics and Gynecology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center at El Paso, El Paso, Texas, United States of America
| | - Michael Scheurer
- Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America
| | - Karen Adler Storthz
- Department of Diagnostic Sciences, School of Dentistry, University of Texas Health Science Center, Houston, Texas, United States of America
| | - Dirk van Niekerk
- Department of Pathology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
| | - Calum E. MacAulay
- Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
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Antic LG, Vukovic DS, Vasiljevic MD, Antic DZ, Aleksopulos HG. Differences in risk factors for cervical dysplasia with the applied diagnostic method in Serbia. Asian Pac J Cancer Prev 2014; 15:6697-701. [PMID: 25169511 DOI: 10.7314/apjcp.2014.15.16.6697] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND In the etiology of cervical cancer not only HPV infection is important, but also other factors such as demographic influences and sexual and reproductive health attitudes, as well as others related to preventive measure usage (or non usage). The aim of this study was to examine factors associated with cervical dysplasia in asymptomatic women who were examined by routine cytology and cervical biopsy for early detection of cervical cancer. MATERIALS AND METHODS Socio-demographic and other characteristics were obtained from medical files of 85 examinees with pathologic cytologic findings (Pap test) and histopathologic (HP) findings after biopsy. RESULTS According to the Pap test result, a greater probability for development of cervical dysplasia was noted with examinees having a larger number of sexual partners (OR= 5.01, 95% CI 1.04-24.10), and those who are afraid of the Pap finding. Risk factors for development of cervical dysplasia according to the bioptic finding were early beginning with sexual activities, presence of any STD in personal medical history and fear of the Pap test finding. CONCLUSIONS The only risk factor found to be important for both methods was fear of the Pap testing finding.
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Affiliation(s)
- Ljiljana Gojko Antic
- Department for Medical Nurses-Midwives, College of Health Studies in Cuprija, Cuprija, Serbia E-mail :
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Amaral CM, Cetkovská K, Gurgel AP, Cardoso MV, Chagas BS, Paiva Júnior SS, de Lima RDCP, Silva-Neto JC, Silva LA, Muniz MT, Balbino VQ, Freitas AC. MDM2 polymorphism associated with the development of cervical lesions in women infected with Human papillomavirus and using of oral contraceptives. Infect Agent Cancer 2014; 9:24. [PMID: 25075210 PMCID: PMC4113664 DOI: 10.1186/1750-9378-9-24] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2014] [Accepted: 06/16/2014] [Indexed: 12/15/2022] Open
Abstract
Background The MDM2 gene is the major negative regulator of p53, a tumor suppressor protein. Single nucleotide polymorphism in promoter region of MDM2 gene leads to increased expression resulting in higher levels of MDM2 protein. This event increases the attenuation of the p53 pathway. Polymorphisms in this gene can interfere in the regulation of cellular proliferation. We evaluated whether MDM2 SNP309 (rs2278744) associated or not with the use of oral contraceptive can heighten susceptibility to development of cervical lesions in women HPV infected. Methods MDM2 SNP309 (rs2278744) was genotyped in a total of 287 patients using the PCR-RFLP technique. The results were analyzed by UNPHASED v.3.121 and SNPStats programs. Results The three groups (SIL, LSIL and HSIL) showed no significant differences in either genotype or allelic frequencies for MDM2 polymorphisms, except when HSIL was compared with LSIL (p = 0.037; OR = 1.81). Furthermore, in the analysis of contraceptives, a significant association was found between the use of contraceptives and the MDM2 variant in the development of high-grade cervical lesions for the TG genotype (p = 0.019; OR = 2.21) when HSIL was compared with control. When HSIL was compared with LSIL (p = 0.006; OR = 2.27). Conclusion The results of this study suggest that MDM2 SNP309 might be a good marker for assessing the progression of LSIL to HSIL. In addition, they also show that oral contraceptives alone, did not have any effect on the progression or development of cervical lesions. However, they may act synergistically with MDM2 SNP309 (rs2278744) and HPV infection in the development of cervical lesions.
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Affiliation(s)
- Carolina Mm Amaral
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Universidade Federal de Pernambuco, Pernambuco, Brazil
| | - Katerina Cetkovská
- Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Ana Pad Gurgel
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Universidade Federal de Pernambuco, Pernambuco, Brazil
| | - Marcus V Cardoso
- Laboratory of Human Molecular Genetics, Department of Genetics, Universidade Federal de Pernambuco, Pernambuco, Brazil
| | - Bárbara S Chagas
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Universidade Federal de Pernambuco, Pernambuco, Brazil
| | - Sérgio Sl Paiva Júnior
- Laboratory of Human Molecular Genetics, Department of Genetics, Universidade Federal de Pernambuco, Pernambuco, Brazil
| | - Rita de Cássia Pereira de Lima
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Universidade Federal de Pernambuco, Pernambuco, Brazil
| | - Jacinto C Silva-Neto
- Molecular and Cytological Research Laboratory, Department of Histology, Universidade Federal de Pernambuco, Pernambuco, Brazil
| | - Luiz Af Silva
- Institute of Biological Sciences and Health, Federal University of Alagoas, Alagoas, Brazil
| | - Maria Tc Muniz
- Laboratory of Molecular Biology of Center of Pediatric Oncohaematological, University of Pernambuco, Pernambuco, Brazil
| | - Valdir Q Balbino
- Laboratory of Human Molecular Genetics, Department of Genetics, Universidade Federal de Pernambuco, Pernambuco, Brazil
| | - Antonio C Freitas
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Universidade Federal de Pernambuco, Pernambuco, Brazil
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Reducing Misclassification Bias in Cervical Dysplasia Risk Factor Analysis With p16-Based Diagnoses. J Low Genit Tract Dis 2014; 18:266-72. [DOI: 10.1097/lgt.0000000000000001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Bowyer HL, Dodd RH, Marlow LAV, Waller J. Association between human papillomavirus vaccine status and other cervical cancer risk factors. Vaccine 2014; 32:4310-6. [PMID: 24950359 PMCID: PMC4103453 DOI: 10.1016/j.vaccine.2014.06.011] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Revised: 05/23/2014] [Accepted: 06/06/2014] [Indexed: 11/18/2022]
Abstract
Little is known about the relationship between HPV vaccine uptake and other risk factors for cervical cancer. This study aimed to measure the association between vaccine status and cervical cancer risk factors in adolescent girls. Girls (15-16 years) from the first two cohorts to be offered routine HPV vaccination in the NHS immunisation programme completed a survey 3 years post-vaccination. Recruitment took place at 13 schools in London. Of 2768 girls registered in Year 11, 1912 (69%) took part and provided analysable data. Questions assessed vaccine status, demographic characteristics, smoking status, sexual behaviour and intention to attend cervical screening. Overall, 78% had completed the three-dose vaccine course. There was no association between vaccine status and smoking behaviour or sexual experience. In adjusted analyses, girls from black or 'other' ethnic backgrounds were less likely to be fully-vaccinated than those from white backgrounds. Those with low intentions to attend cervical screening were less likely to be fully vaccinated than those with high intentions. Efforts will be needed to ensure that unvaccinated women understand the importance of cervical screening when they reach the age that screening begins. Ethnic inequalities in vaccine coverage need to be explored further.
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Affiliation(s)
- Harriet L Bowyer
- Health Behaviour Research Centre, Department of Epidemiology & Public Health, UCL, Gower Street, London WC1E 6BT, United Kingdom
| | - Rachael H Dodd
- Health Behaviour Research Centre, Department of Epidemiology & Public Health, UCL, Gower Street, London WC1E 6BT, United Kingdom
| | - Laura A V Marlow
- Health Behaviour Research Centre, Department of Epidemiology & Public Health, UCL, Gower Street, London WC1E 6BT, United Kingdom
| | - Jo Waller
- Health Behaviour Research Centre, Department of Epidemiology & Public Health, UCL, Gower Street, London WC1E 6BT, United Kingdom.
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Chen Z, Meng W, DU R, Zhu Y, Zhang Y, Ding Y. Genotype distribution and the relative risk factors for human papillomavirus in Urumqi, China. Exp Ther Med 2013; 6:85-90. [PMID: 23935724 PMCID: PMC3735662 DOI: 10.3892/etm.2013.1073] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2013] [Accepted: 04/11/2013] [Indexed: 11/05/2022] Open
Abstract
The aim of this study was to investigate human papillomavirus (HPV) infection and HPV genotype distributions in Urumqi, Xinjiang, China. The related risk factors for high-risk HPV infection was also analyzed. A stratified cluster sampling method was used for the population-based cervical cancer screening of women aged 18-69 years in the Urumqi Saybagh district. Exfoliated cervical cell samples were collected for liquid-based cytology detection and HPV genotyping DNA microarrays. Education level, number of sexual partners, condom use and occupation were used in the multivariate analysis model. The HPV infection rate of women working in service industries was significantly higher compared with those of white-collar workers, community residents and migrant workers. The 35-44-year-old migrant worker group had the highest HPV infection rates among all of the groups in the three different age ranges. The number of marriages, education level, smoking history, number of abortions, use of condoms, number of sexual partners, number of sexual partners in the past five years and occupation were all associated with female HPV infection rate (P<0.05). The 35-44-year-old women were the age group with the highest HPV infection rate. The HPV infection rate of females in service industries was the highest. Education level and condom use were protective factors of HPV infection, while the number of sexual partners and occupation were risk factors for HPV infection.
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Affiliation(s)
- Zhifang Chen
- Xiangya Hospital, Central South University, Changsha, Hunan 410000; ; Gynecology Department, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
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Remschmidt C, Kaufmann AM, Hagemann I, Vartazarova E, Wichmann O, Deleré Y. Risk factors for cervical human papillomavirus infection and high-grade intraepithelial lesion in women aged 20 to 31 years in Germany. Int J Gynecol Cancer 2013; 23:519-26. [PMID: 23360813 DOI: 10.1097/igc.0b013e318285a4b2] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Persistent infection with high-risk human papillomaviruses (HPVs) can lead to cervical intraepithelial lesion and cervical cancer. Sexual behavior and smoking have been identified as risk factors for HPV infection. However, it is unclear which factors account for the persistence of HPV infection and for high-grade squamous intraepithelial lesions (HSIL). Therefore, we conducted a study to identify epidemiological risk factors for the following: (1) the presence of HPV among women without a recent diagnosis of HSIL and (2) HSIL. MATERIALS AND METHODS Participants aged 20 to 31 years were recruited at 2 study sites. All women received a cervical Papanicolaou test, were tested for HPV, and categorized into 1 of 3 different groups: The women of the first group had negative cytological test results and a negative HPV test result (HPV-negative group), and the women of the second group had negative cytological test result but positive HPV test result (HPV-positive group). The third group consisted of women with a diagnosis of HSIL (HSIL group). We first compared the HPV-negative group with the HPV-positive group, and then the HPV-positive group with the HSIL group. RESULTS One hundred forty-seven women were included: 53 women in the HPV-negative group, 46 women in the HPV-positive group, and 48 women in the HSIL group. Comparing the HPV-negative with the HPV-positive group, we found that more than 5 sexual partners during a lifetime were independently associated with cervical HPV infection, whereas the chance of being infected decreased with older age. Irregular condom use during one-night stands or smoking was associated with HPV infection only in univariable but not multivariable analysis. In contrast, older age and having had genital warts were independently associated with an HSIL diagnosis when comparing the HPV-positive group with the HSIL group. DISCUSSION Although the study was hampered by its relatively small sample size, our data suggest that main risk factors for the acquisition of HPV infection are a higher number of sexual partners and younger age, whereas older age and genital warts may be epidemiological cofactors in the development of HSIL.
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Prabhu SR, Wilson DF. Human papillomavirus and oral disease - emerging evidence: a review. Aust Dent J 2013; 58:2-10; quiz 125. [PMID: 23441786 DOI: 10.1111/adj.12020] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/18/2012] [Indexed: 12/15/2022]
Abstract
Human papillomavirus (HPV) infections have received considerable attention in recent years. Of the 120 or so known types of the virus, some cause a variety of benign wart-like lesions of the skin and genital and oral mucosae, whilst others are aetiologically associated with cervical and anogenital cancers. Recent epidemiologic evidence suggests that HPV may also be an independent risk factor for oropharyngeal cancer. In this context it has been suggested that HPV virus may modulate the process of carcinogenesis in some tobacco and alcohol induced oropharyngeal cancers and act as the primary oncogenic agent for inducing carcinogenesis among non-smokers. Dental practitioners have a major role in detecting all lesions of the oral mucosa caused, or possibly caused, by HPV. This paper briefly reviews the current state of knowledge of molecular and clinical aspects of HPV infections of the oral mucosa.
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Affiliation(s)
- S R Prabhu
- School of Dentistry and Health Sciences, Charles Sturt University, Orange, New South Wales.
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Parity as a cofactor for high-grade cervical disease among women with persistent human papillomavirus infection: a 13-year follow-up. Br J Cancer 2012; 108:234-9. [PMID: 23169283 PMCID: PMC3553518 DOI: 10.1038/bjc.2012.513] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Background: Several environmental factors have been associated with increased risks for cervical cancer. We examined whether reproductive history, contraceptive use, or sexual behaviour increase the risk for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among women with persistent human papillomavirus (HPV) infection. Methods: A population-based cohort of women participated in a personal interview and underwent a gynaecological examination at which cervical specimens were obtained for HPV DNA testing. Follow-up information (∼13 years) on cervical lesions was obtained from the Danish Pathology Data Bank. Women who had a high-risk HPV infection comprised the overall study population (n=1353). A subgroup of women with persistent high-risk HPV infection (n=312) was identified. Hazard ratios (HRs) for a diagnosis of CIN3+ and the corresponding 95% confidence intervals (CIs) were calculated. Results: Women with persistent HPV infection who had given birth had a significantly increased risk for CIN3+ (HR=1.78; 95% CI: 1.07–2.94). No association was found with pregnancy, use of intrauterine devices, or sexual behaviour. Based on small numbers, women with persistent HPV infection had a decreased risk for CIN3+ with any use of oral contraceptives (HR=0.54; 95% CI: 0.29–1.00). Conclusion: Childbirth increases the risk for subsequent CIN3+ among women with persistent HPV infection.
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Luu HN, Amirian ES, Beasley RP, Piller L, Chan W, Scheurer ME. Association between smoking and size of anal warts in HIV-infected women. Int J STD AIDS 2012; 23:792-8. [PMID: 23155099 PMCID: PMC4629988 DOI: 10.1258/ijsa.2012.011420] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
While the association between smoking and human papillomavirus infection, cervical cancer, and anal cancer has been well studied, evidence on the association between cigarette smoking and anal warts is limited. The purpose of this study was to investigate if cigarette smoking status influences the size of anal warts over time in HIV-infected women in a sample of 976 HIV-infected women from the Women's Interagency HIV Study (WIHS). A linear mixed model was used to determine the effect of smoking on anal wart size. Even though women who were currently smokers had larger anal warts at baseline and slower growth rate of anal wart size after each visit than women who were not current smokers, there was no association between size of anal wart and current smoking status over time. Further studies on the role of smoking and interaction between smoking and other risk factors, however, should be explored.
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Affiliation(s)
- H N Luu
- Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA
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Sakata R, Kleinerman RA, Mabuchi K, Stovall M, Smith SA, Weathers R, Wactawski-Wende J, Cookfair DL, Boice JD, Inskip PD. Cancer Mortality Following Radiotherapy for Benign Gynecologic Disorders. Radiat Res 2012; 178:266-79. [DOI: 10.1667/rr2845.1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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Gadducci A, Guerrieri ME, Greco C. Tissue biomarkers as prognostic variables of cervical cancer. Crit Rev Oncol Hematol 2012; 86:104-29. [PMID: 23031678 DOI: 10.1016/j.critrevonc.2012.09.003] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2012] [Revised: 07/02/2012] [Accepted: 09/04/2012] [Indexed: 01/05/2023] Open
Abstract
The most important prognostic variables of cervical carcinoma are FIGO stage, lymph node status and clinical-pathological features of primary tumor. Recently, there has been increasing interest in the identification of biomarkers able to predict both response to treatment and survival. The aim of this review is to critically evaluate current published evidence on the ability of various tissue biomarkers to predict the clinical outcome of patients with cervical carcinoma. In particular, the paper takes into account DNA content, cell-cycle and apoptosis-regulatory proteins, epidermal growth factor receptor [EGFR], vascular endothelial growth factor [VEGF], cyclooxygenase [COX]-2, signal transducer and activator of transcription [Stat]3, human papilloma virus [HPV] status, tumor hypoxia, tumor infiltrating lymphocytes [TIL], microarray technology and microRNA (miRNA). The presence of HPV-18 genotype and an elevated VEGF expression appear to be poor prognostic factors in women with early disease treated with primary surgery, whereas the expression of EGFR, VEGF, COX-2 and tumor hypoxia may have a major impact on the survival of patients treated with definitive radiotherapy or chemoradiation. The data supporting the reliability of ΔNp73 and TAp73α as novel biomarkers of response to radiotherapy are interesting but still limited. DNA microarray technology could offer new laboratory tools for a rationale planning of treatment strategy, and miRNAs might represent new candidate targets to be investigated for both prognostic and therapeutic purposes. Moreover, the assessment of different types of TIL and their ligands in tumor biopsies could enable the identification of a subset of high-risk patients, paving the way to novel immune therapies aimed at blocking T-reg cell activity.
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Affiliation(s)
- Angiolo Gadducci
- Department of Procreative Medicine, Division of Gynecology and Obstetrics, University of Pisa, Italy.
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Jensen KE, Schmiedel S, Frederiksen K, Norrild B, Iftner T, Kjær SK. Risk for cervical intraepithelial neoplasia grade 3 or worse in relation to smoking among women with persistent human papillomavirus infection. Cancer Epidemiol Biomarkers Prev 2012; 21:1949-55. [PMID: 23019238 DOI: 10.1158/1055-9965.epi-12-0663] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Smoking has been associated with cervical cancer. We examined whether smoking increases the risk for high-grade cervical lesions in women with high-risk human papillomavirus (HPV) infection. METHODS In a population-based cohort study, 8,656 women underwent a structured interview, and subsequently cervical cells were obtained for HPV DNA testing. Women with high-risk HPV infection and no prevalent cervical disease at baseline (n = 1,353) were followed through the Pathology Data Bank for cervical lesions for up to 13 years. Separate analyses of women with persistent high-risk HPV infection (n = 312) were also conducted. HRs for a diagnosis of cervical intraepithelial neoplasia grade 3 or worse/high-grade squamous intraepithelial lesions or worse (CIN3+) and the corresponding 95% confidence intervals (CI) were calculated in the two groups. RESULTS Among high-risk HPV-positive women, an increased risk for CIN3+ was associated with long-term smoking (≥10 years) and heavy smoking (≥20 cigarettes/d). In the subgroup of women with persistent HPV infection, heavy smoking was also associated with a statistically significantly higher risk for CIN3+ than never smoking (HR, 1.85; 95% CI, 1.05-3.22, adjusted for length of schooling, parity, and HPV type at baseline). The average number of cervical cytology screening tests per year during follow-up did not explain the differences in risk in relation to smoking (P = 0.4). CONCLUSIONS Smoking is associated with an increased risk for subsequent high-grade cervical lesions in women with persistent high-risk HPV infection. IMPACT Our study adds to the understanding of the role of smoking in the natural history of HPV and cervical carcinogenesis.
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Kelava I, Tomicić K, Kokić M, Corusić A, Planinić P, Kirac I, Murgić J, Kulis T, Znaor A. Breast and gynecological cancers in Croatia, 1988-2008. Croat Med J 2012; 53:100-8. [PMID: 22522987 PMCID: PMC3342654 DOI: 10.3325/cmj.2012.53.100] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Aim To analyze and interpret incidence and mortality trends of breast and ovarian cancers and incidence trends of cervical and endometrial cancers in Croatia for the period 1988-2008. Methods Incidence data were obtained from the Croatian National Cancer Registry. The mortality data were obtained from the World Health Organization (WHO) mortality database. Trends of incidence and mortality were analyzed by joinpoint regression analysis. Results Joinpoint analysis showed an increase in the incidence of breast cancer with estimated annual percent of change (EAPC) of 2.6% (95% confidence interval [CI], 1.9 to 3.4). The mortality rate was stable, with the EAPC of 0.3% (95% CI, -0.6 to 0.0). Endometrial cancer showed an increasing incidence trend, with EAPC of 0.8% (95% CI, 0.2 to 1.4), while cervical cancer showed a decreasing incidence trend, with EAPC of -1.0 (95% CI, -1.6 to -0.4). Ovarian cancer incidence showed three trends, but the average annual percent change (AAPC) for the overall period was not significant, with a stable trend of 0.1%. Ovarian cancer mortality was increasing since 1992, with EAPC of 1.2% (95% CI, 0.4 to 1.9), while the trend for overall period was stable with AAPC 0.1%. Conclusion Incidence trends of breast, endometrial, and ovarian cancers in Croatia 1988-2008 are similar to the trends observed in most of the European countries, while the modest decline in cervical cancer incidence and lack of decline in breast cancer mortality suggest suboptimal cancer prevention and control.
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Affiliation(s)
- Iva Kelava
- Croatian National Institute of Public Health, Rockefellerova 7, 10000 Zagreb, Croatia
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