Roles of extended human papillomavirus genotyping and multiple infections in early detection of cervical precancer and cancer and HPV vaccination

Abstract Background The aim of the study was to investigate the risk of human papillomavirus (HPV) genotyping particularly vaccine genotypes and multiple infections for cervical precancer and cancer, which might contribute to developing genotype-specific screening strategy and assessing potential effects of HPV vaccine. Methods The HPV genotypes were identified using the Seq HPV assay on self-collected samples. Hierarchical ranking of each genotype was performed according to positive predictive value (PPV) for cervical intraepithelial neoplasia 2/3 or worse (CIN2+/CIN3+). Multivariate logistic regression model was used to estimate the odds ratios (ORs) with 95% confidence interval (CI) of CIN2+ according to multiplicity of types and vaccine types. Results A total of 2811 HPV-positive women were analyzed. The five dominant HPV genotypes in high-grade lesions were 16/58/52/33/18. The overall ranking orders were HPV16/33/35/58/31/68/18/ 56/52/66/51/59/45/39 for CIN2+ and HPV16/33/31/58/45/66/52/18/35/56/51/68/59/39 for CIN3+. The risks of single infection versus co-infections with other types lower in the hierarchy having CIN2+ were not statistically significant for HPV16 (multiple infection vs. single infection: OR = 0.8, 95%CI = 0.6-1.1, P = 0.144) or other genotypes (P > 0.0036) after conservative Bonferroni correction. Whether HPV16 was present or not, the risks of single infection versus multiple infection with any number (2, ≥2, or ≥ 3) of types for CIN2+ were not significantly different. In addition, HPV31/33/45/52/58 covered by nonavalent vaccine added 27.5% of CIN2, 23.0% of CIN3, and 12.5% of cancer to the HPV16/18 genotyping. These genotype-groups were at significantly higher risks than genotypes not covered by nonavalent vaccine. Moreover, genotypes covered by nonavalent vaccine contributed to 85.2% of CIN2 lesions, 97.9% of CIN3 and 93.8% of cancers. Conclusions Partial extended genotyping such as HPV33/31/58 but not multiplicity of HPV infections could serve as a promising triage for HPV-positive self-samples. Moreover, incidence rates of cervical cancer and precancer were substantial attributable to HPV genotypes covered by current nonavalent vaccination.

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Human pappilomavirus genotype in cervical tissue of patients with Cervical Intraepithelial Neoplasia (CIN) 1, CIN 2, and CIN 3

Majalah Obstetri & Ginekologi ◽

10.20473/mog.v24i32016.74-78 ◽

2018 ◽

Vol 24 (3) ◽

pp. 74

Author(s):

Gondo Mastutik ◽

Rahmi Alia ◽

Alphania Rahniayu ◽

Anny Setijo Rahaju ◽

Renny I’tishom ◽

...

Keyword(s):

Precancerous Lesions ◽

Intraepithelial Neoplasia ◽

Cross Sectional Study ◽

Single Infection ◽

Multiple Infections ◽

Cervical Tissue ◽

Cross Sectional ◽

Hpv Dna ◽

Hpv Genotypes ◽

Paraffin Block

Objectives: to determine the genotype of HPV in patients with precancerous lesions of cervical tissue.Materials and Methods: An observational study with cross sectional study of patients paraffin block CIN1, CIN2, CIN3 was conducted in Dr Soetomo Hospital. HPV DNA was extracted from paraffin blocks, then performed PCR and genotyping of HPV. The sample consisted of 28 patients with cervical tissue paraffin blocks CIN1, CIN2 and CIN3. Patients aged between 26-74 years (standard deviation 10,12).Results: HPV genotypes that infect patients with CIN1 were HPV16 and 18, CIN2 were HPV16 and 52 and CIN3 were HPV16, 67, and combined infection HPV16/67 and HPV52/67. HPV genotypes in a single infection were 26/28 (HPV16, HPV18, HPV52 and HPV67), and multiple infections were 2/28 (HPV16/67 and HPV52/67).Conclusion: The most dominant HPV genotypes infect patients with precancerous lesions of the cervix were HPV16, HPV67, HPV52, and HPV18.

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The Prevalence and Distribution of High Risk Human Papillomavirus Genotypes in Patients with Dysplastic Lesions: a Population Study

Acta Medica Marisiensis ◽

10.1515/amma-2015-0107 ◽

2015 ◽

Vol 61 (4) ◽

pp. 314-319

Author(s):

Voidăzan Septimiu ◽

Morariu Silviu-Horia ◽

Căpâlnă Mihai ◽

Mărginean Claudiu ◽

Dobreanu Minodora

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Public Health Problem ◽

Hpv Infection ◽

Single Infection ◽

Multiple Infections ◽

Major Public Health Problem ◽

Hpv Genotypes ◽

Hpv Types ◽

High Risk Hpv

AbstractBackground. Cervical cancer (CC) is a major public health problem worldwide. Knowledge of human papillomavirus (HPV) genotype prevalence and distribution is important for the introduction of an effective vaccination program and the corresponding epidemiological monitoring. The aim of this study was to identify and analyze the distribution of high-risk HPV genotypes.Methods. Data were collected from 136 patients for the detection of circulating HPV genotypes, where Pap test results revealed the presence of koilocytes or high risk (HR) dysplastic lesions, elements that raise the suspicion of HPV infection.Results. HPV infection was identified in 72 (55.4%) of the patients tested, 34 (47.3%) with single infection, and 38 (52.7%) with multiple infections. Twenty-two different types of HPV were identified: 14 high risk HPV types, 7 low risk HPV types, 1 probable high risk HPV type. HPV 16 was the most frequently detected (55.6%) one, it was involved in single (15 cases) and multiple (25 cases) infections, primarily associated with type 18 (12 cases), and type 52 (11 cases). The presence of HPV 18 (29.2%) and HPV 52 (23.6%) was identified after HPV type 16.Conclusions. Oncogenic HPV genotypes 16, 18, and 52 were most frequently associated in women with dysplastic lesions, which require the use of polyvalent HPV vaccines when assessing cross-protective effects of specific immunoprophylaxis programs.

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Human pappilomavirus genotype in cervical tissue of patients with Cervical Intraepithelial Neoplasia (CIN) 1, CIN 2, and CIN 3

Majalah Obstetri & Ginekologi ◽

10.20473/mog.v24i3.4568 ◽

2017 ◽

Vol 24 (3) ◽

pp. 74

Author(s):

Gondo Mastutik ◽

Rahmi Alia ◽

Alphania Rahniayu ◽

Anny Setijo Rahaju ◽

Renny I’tishom

Keyword(s):

Precancerous Lesions ◽

Intraepithelial Neoplasia ◽

Cross Sectional Study ◽

Single Infection ◽

Multiple Infections ◽

Cervical Tissue ◽

Cross Sectional ◽

Hpv Dna ◽

Hpv Genotypes ◽

Paraffin Block

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Phylogenetic classification of human papillomavirus genotypes in high-grade cervical intraepithelial neoplasia in women from a densely populated Brazilian urban region

Sao Paulo Medical Journal ◽

10.1590/s1516-31802009000300003 ◽

2009 ◽

Vol 127 (3) ◽

pp. 122-127 ◽

Cited By ~ 5

Author(s):

Denise Rocha Pitta ◽

Luis Otávio Sarian ◽

Elisabete Aparecida Campos ◽

Sílvia Helena Rabelo-Santos ◽

Kari Syrjänen ◽

...

Keyword(s):

Human Papillomavirus ◽

Cervical Intraepithelial Neoplasia ◽

Intraepithelial Neoplasia ◽

Multiple Infections ◽

High Grade ◽

Hpv 16 ◽

Phylogenetic Classification ◽

Hpv Genotypes ◽

Hpv Types ◽

Hpv 18

CONTEXT AND OBJECTIVE: Differences in human papillomavirus (HPV) types may correlate with the biological potential and invasion risk of high-grade cervical intraepithelial neoplasia (CIN 2 and CIN 3). The objective of this study was to determine the relationship between different combinations of HPV types and CIN severity. DESIGN AND SETTING: Cross-sectional study, at Universidade Estadual de Campinas (Unicamp). METHODS: Cervical samples from 106 women treated due to CIN 2 (18) or CIN 3 (88) were examined for specific HPV genotypes using Roche Linear Array® (LA-HPV). The proportions of CIN 2 and CIN 3 in groups of women infected with the HPV phylogenetic groups A7 and A9 were compared. Three groups were formed: women with single infections; multiple infections; and the whole sample. RESULTS: Multiple infections were detected in 68 samples (64.7%). The most frequent high-risk genotypes detected (single/multiple) were HPV 16 (57.1%), HPV 58 (24.7%), HPV 33 (15.2%), HPV 52 (13.3%), HPV 31 (10.4%), HPV 51 (7.6%) and HPV 18 (6.6%). Women without infection with HPV species Alpha 9 were less likely to have CIN 3 than were their Alpha 9 HPV-infected counterparts. HPV 16 and/or HPV 18, with or without associations with other viral types, were more frequently found in women with CIN 3 than in those with CIN 2. CONCLUSIONS: The severity of high-grade CIN may be aggravated by the presence of HPV types included in the Alpha 9 phylogenetic classification and by infections including HPV 16 and 18, singly or in combination with other HPV genotypes.

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Human Papillomavirus Type Distribution in Cervical Intraepithelial Neoplasia Grade 2/3 and Cervical Cancer in Portugal: A CLEOPATRE II Study

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e318280f26e ◽

2013 ◽

Vol 23 (3) ◽

pp. 500-506 ◽

Cited By ~ 13

Author(s):

Angela Pista ◽

Carlos Freire de Oliveira ◽

Carlos Lopes ◽

Maria João Cunha

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

High Risk ◽

Cervical Intraepithelial Neoplasia ◽

Invasive Cervical Cancer ◽

Intraepithelial Neoplasia ◽

Multiple Infections ◽

Hpv 16 ◽

Specific Distribution ◽

Hpv Genotypes

ObjectiveCervical cancer is the third most frequent cancer in women, worldwide and etiologically associated with infection by human papillomavirus (HPV). Following the results of the first epidemiologic population-based CLEOPATRE study in Portugal, it was important to understand the HPV type-specific distribution in women with cervical intraepithelial neoplasia (CIN) grades 2 and 3 and invasive cervical cancer (ICC).MethodsThis was an observational, multicenter, cross-sectional study with retrospective data collection. Between January 2008 and May 2009, paraffin-embedded samples of histologically confirmed cases of CIN2, CIN3, and ICC were collected from the 5 regional health administrations in mainland Portugal. Eligible samples were sent to 2 central laboratories for histological reassessment and HPV genotyping. Prevalence estimates were calculated together with 95% confidence intervals.ResultsA total of 582 samples, 177 cases of CIN2, 341 of CIN3, and 64 of ICC, were included. The mean age of participants was 41.8 years (range, 20–88 years). The overall HPV prevalence was 97.9% with a higher prevalence of high-risk genotypes, particularly HPV 16. Multiple infections were observed in 11.2% of the cases. Human papillomavirus prevalence was 95.5% in CIN2, 99.4% in CIN3, and 96.9% in ICC. The 8 more frequent genotypes in order of decreasing frequency were HPV 16, 31, 58, 33, 51, 52, 18, and 35 in CIN2 and HPV 16, 31, 33, 58, 52, 35, 18, and 51 in CIN3. In ICC cases, the 12 detected HPV genotypes were HPV 16, 18, 31, 33, 45, 51, 52, 53, 56, 58, 59, and 73. However, HPV 53 and 73 were always associated to other high-risk genotypes. Human papillomavirus types 31, 51, 52, 56, and 59 were detected in 1 case each.ConclusionsHuman papillomavirus prevalence and patterns of type-specific HPV positivity were comparable with other studies. Current HPV vaccines should protect against HPV genotypes responsible for 77.4% of ICC in Portugal.

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Prevalence of Human Papillomavirus (HPV) Genotypes and Multiple Infections in Routine Cervical Cancer Screening in a Spanish Regional Population

SOJ Microbiology & Infectious Diseases ◽

10.15226/sojmid.2013.00105 ◽

2013 ◽

Vol 1 (1) ◽

Author(s):

Toro de Morelva Mendez

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Multiple Infections ◽

Hpv Genotypes ◽

Regional Population

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Human papillomavirus vaccination: evidence base for efficacy and safety

GYNECOLOGY ◽

10.26442/20795696.2021.2.200742 ◽

2021 ◽

Vol 23 (2) ◽

pp. 125-130

Author(s):

Yuliya E. Dobrokhotova ◽

Ekaterina I. Borovkova

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Hpv Vaccination ◽

Intraepithelial Neoplasia ◽

Evidence Base ◽

Hpv Infection ◽

Efficacy And Safety ◽

Human Papillomavirus Vaccination ◽

Hpv Types ◽

Further Development

The article provides a literature review on the prevention of cervical cancer by human papillomavirus (HPV) vaccination. Currently, 3 vaccines are available: the 4-valent vaccine against HPV types 6, 11, 16 and 18, the 9-valent vaccine against HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58 and the bivalent vaccine against HPV types 16 and 18. Vaccination provides protection for women and men against infection with HPV and further development of HPV-associated diseases. Following immunization, seroconversion develops in 93-100% of women and in 99-100% of men and is effective in preventing incident and persistent HPV infection as well as cervical intraepithelial neoplasia. HPV immunization is ineffective in treating an existing HPV infection, genital warts, or anogenital intraepithelial neoplasia. HPV vaccination status does not affect recommendations for cervical cancer screening.

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Comparison of Human Papillomavirus Genotypes in Penile Intraepithelial Neoplasia and Associated Lesions: LCM-PCR Study of 87 Lesions in 8 Patients

International Journal of Surgical Pathology ◽

10.1177/1066896919887802 ◽

2019 ◽

Vol 28 (3) ◽

pp. 265-272 ◽

Cited By ~ 2

Author(s):

María José Fernández-Nestosa ◽

Nuria Guimerà ◽

Diego F. Sanchez ◽

Sofía Cañete-Portillo ◽

Antonella Lobatti ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Precancerous Lesions ◽

Intraepithelial Neoplasia ◽

Associated Lesions ◽

Hpv Genotypes ◽

Flat Lesions ◽

High Risk Hpv ◽

Intraepithelial Lesions ◽

Penile Intraepithelial Neoplasia

Penile intraepithelial neoplasia (PeIN) is currently classified in human papillomavirus (HPV)- and non-HPV-related subtypes with variable HPV genotypes. PeINs are frequently associated with other intraepithelial lesions in the same specimen. The aim of this study was to detect and compare HPV genotypes in PeINs and associated lesions using high-precision laser capture microdissection-polymerase chain reaction and p16INK4a immunostaining. We evaluated resected penile specimens from 8 patients and identified 33 PeINs and 54 associated lesions. The most common subtype was warty PeIN, followed by warty-basaloid and basaloid PeIN. Associated lesions were classical condylomas (17 cases), atypical classical condylomas (2 cases), flat condylomas (9 cases), atypical flat condylomas (6 cases), flat lesions with mild atypia (12 cases), and squamous hyperplasia (8 cases). After a comparison, identical HPV genotypes were found in PeIN and associated lesions in the majority of the patients (7 of 8 patients). HPV16 was the most common genotype present in both PeIN and corresponding associated lesion (50% of the patients). Nonspecific flat lesions with mild atypia, classical condylomas, and atypical condylomas were the type of associated lesions most commonly related to HPV16. Other high-risk HPV genotypes present in PeIN and associated nonspecific flat lesion with mild atypia were HPV35 and HPV39. In this study of HPV in the microenvironment of penile precancerous lesions, we identified identical high-risk HPV genotypes in PeIN and classical, flat, or atypical condylomas and, specially, in nonspecific flat lesions with mild atypia. It is possible that some of these lesions represent hitherto unrecognized precancerous lesions.

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Comprehensive Human Papillomavirus Genotyping in Cervical Squamous Cell Carcinomas and Its Relevance to Cervical Cancer Prevention in Malawian Women

Journal of Global Oncology ◽

10.1200/jgo.2015.001909 ◽

2017 ◽

Vol 3 (3) ◽

pp. 227-234 ◽

Cited By ~ 4

Author(s):

Brooke E. Howitt ◽

Michael Herfs ◽

Tamiwe Tomoka ◽

Steve Kamiza ◽

Tarik Gheit ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Squamous Cell ◽

Vaccine Development ◽

Hpv Vaccination ◽

Significant Proportion ◽

Sub Saharan Africa ◽

Single Infection ◽

Hpv 16 ◽

Hpv Types

Purpose Cervical squamous cell carcinoma (SCC) continues to be a significant cause of cancer morbidity and is the third leading cause of cancer-related death in women worldwide. In sub-Saharan Africa, cervical cancer is not only the most common female cancer but also the leading cause of cancer-related deaths in women. Malawi, in particular, has the highest burden of cervical cancer. With the increasing use of human papillomavirus (HPV) vaccination, documenting the prevalent HPV types in those high-risk populations is necessary to both manage expectations of HPV vaccination and guide future vaccine development. Materials and Methods In this study, we performed HPV typing on 474 cervical SCC samples and analyzed the potential impact of HPV vaccination in this population. Results Ninety-seven percent of tumors were positive for at least one HPV type, and 54% harbored more than one HPV type. HPV 16 was the most common type (82%), followed by HPV 18 (34%), HPV 35 (24%), and HPV 31 (12%). A vaccine against HPV 16 and 18 would ideally prevent 53% of cervical SCC, and the nonavalent HPV vaccine (covering HPV 16, 18, 31, 33, 45, 52, and 58) would prevent 71% of cervical SCC in Malawi (assuming 100% vaccine efficacy). The main reason for a lack of coverage was high prevalence of HPV 35, which was also present as a single infection in a small subset of patients. Conclusion Although any HPV vaccination in this population would likely prevent a significant proportion of cervical cancer, the nonavalent vaccine would provide better coverage. Furthermore, investigation of the role of HPV 35 in this population, including possible cross-protection with other HPV types, should be pursued.

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