scholarly journals Differential expression of human papillomavirus 16-, 18-, 52-, and 58-derived transcripts in cervical intraepithelial neoplasia

2020 ◽  
Author(s):  
Satoshi Baba ◽  
Ayumi Taguchi ◽  
Akira Kawata ◽  
Konan Hara ◽  
Satoko Eguchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Detection Rate ◽  
Expression Patterns ◽  
Epidemiologic Study ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Hpv 16 ◽  
Hpv Genotypes

Abstract Background Human papillomavirus (HPV) infection is a primary cause of cervical cancer. Although epidemiologic study revealed that carcinogenic risk differs according to HPV genotypes, the expression patterns of HPV-derived transcripts and their dependence on HPV genotypes have not yet been fully elucidated. Methods In this study, 382 patients with abnormal cervical cytology were enrolled to assess the associations between HPV-derived transcripts and cervical intraepithelial neoplasia (CIN) grades and/or HPV genotypes. Specifically, four HPV-derived transcripts, namely, oncogenes E6 and E6* , E1^E4 , and viral capsid protein L1 in four major HPV genotypes—HPV 16, 18, 52, and 58—were investigated. Results The detection rate of E6/E6* increased with CIN progression, whereas there was no significant change in the detection rate of E1^E4 or L1 among CIN grades. In addition, we found that L1 gene expression was HPV type-dependent. Almost all HPV 52-positive specimens, approximately 50% of HPV 58-positive specimens, around 33% of HPV 16-positive specimens, and only one HPV18-positive specimen expressed L1 . Conclusions We demonstrated that HPV-derived transcripts are HPV genotype-dependent. Especially, expression patterns of L1 gene expression might reflect HPV genotype-dependent patterns of carcinogenesis.

scholarly journals Differential expression of human papilloma virus 16-, 18-, 52-, and 58-derived transcripts in cervical intraepithelial neoplasia

2020 ◽  
Author(s):  
Satoshi Baba ◽  
Ayumi Taguchi ◽  
Akira Kawata ◽  
Konan Hara ◽  
Satoko Eguchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Intraepithelial Neoplasia ◽  
Detection Rate ◽  
Expression Patterns ◽  
Epidemiologic Study ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Carcinogenic Risk ◽  
Hpv 16 ◽  
Hpv Genotypes

Abstract Background: Human papillomavirus (HPV) infection is a primary cause of cervical cancer. Although epidemiologic study revealed that carcinogenic risk differs according to HPV genotypes, the expression patterns of HPV-derived transcripts and their dependence on HPV genotypes have not yet been fully elucidated.Methods: In this study, 382 patients with abnormal cervical cytology were enrolled to assess the associations between HPV-derived transcripts and cervical intraepithelial neoplasia (CIN) grades and/or HPV genotypes. Specifically, four HPV-derived transcripts, namely, oncogenes E6 and E6*, E1^E4, and viral capsid protein L1 in four major HPV genotypes—HPV 16, 18, 52, and 58—were investigated.Results: The detection rate of E6/E6* increased with CIN progression, whereas there was no significant change in the detection rate of E1^E4 or L1 among CIN grades. In addition, we found that L1 gene expression was HPV type-dependent. Almost all HPV 52-positive specimens, approximately 50% of HPV 58-positive specimens, around 33% of HPV 16-positive specimens, and only one HPV18-positive specimen expressed L1.Conclusions: We demonstrated that HPV-derived transcripts are HPV genotype-dependent. Especially, expression patterns of L1 gene expression might reflect HPV genotype-dependent patterns of carcinogenesis.

scholarly journals Correlation between Human Papillomavirus Codetection Profiles and Cervical Intraepithelial Neoplasia in Japanese Women

2020 ◽  
Vol 8 (12) ◽  
pp. 1863
Author(s):  
Kaori Okayama ◽  
Hirokazu Kimura ◽  
Koji Teruya ◽  
Yasuyoshi Ishii ◽  
Kiyotaka Fujita ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Hpv Genotypes ◽  
High Risk Type ◽  
Pcr Method ◽  
Polymerase Chain ◽  
High Risk Hpv

Human papillomavirus (HPV) infection is thought to be strongly associated with the precarcinomatous state cervical intraepithelial neoplasia (CIN) and cervical carcinoma. To accurately assess the correlation between HPV detection profiles and CIN, the uniplex E6/E7 polymerase chain reaction (PCR) method was used. We detected HPV (37 genotypes) in 267 CIN cases. The detection of a single high-risk HPV genotype occurred in 69.7% of CIN1 and worse than CIN1 (CIN1+) cases whereas other types were detected in 11.6% of cases. Codetection of high-risk HPV genotypes occurred in 4.9% of CIN1+ cases. The high-risk genotype HPV16 was the most frequently detected genotype in CIN1+ lesions; the genotype HPV34 (not a high-risk type) was detected in some CIN3 cases. Furthermore, HPV codetection may not be associated with CIN grades. These results suggest that various HPV genotypes are associated with CIN across all analyzed cases.

scholarly journals HES1 Protein Modulates Human Papillomavirus–Mediated Carcinoma of the Uterine Cervix

2019 ◽  
pp. 1-10 ◽  
Author(s):  
Richa Tripathi ◽  
Gayatri Rath ◽  
Vishwas Sharma ◽  
Showket Hussain ◽  
Shashi Sharma ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Invasive Squamous Cell Carcinoma ◽  
Hpv 16 ◽  
Notch 3 ◽  
Gynecology And Obstetrics ◽  
Hes1 Expression ◽  
Histologic Subtypes

PURPOSE Cervical cancer (CC) is the most common cancer affecting women worldwide. Human papillomavirus (HPV) infection is a major contributing factor for the development of CC. The development of CC occurs progressively from precancer stages to cancerous stages (ie, invasive squamous cell carcinoma [ISCC] and adenocarcinoma [ADC]). ADC is a rare form of CC that develops from the mucinous endocervical epithelium. It is believed that the downstream targets of Notch signaling contribute to the etiology of CC. One such target is HES1, whose role in the modulation of ADC is unknown. The purpose of this study is to determine the role of HES1 protein in HPV-associated ADC subtype of CC and also to compare its expression in histologic subtypes of precancer and ISCC. PATIENTS AND METHODS A total of 148 patients (30 with precancers, 98 with ISCC, and 20 with ADC) and 40 normal control participants were analyzed for the expression of HES1 via immunohistochemistry, with results validated by immunoblotting. RESULTS The comparison between HPV-16 and HES1 expression was significant in precancer (cervical intraepithelial neoplasia grades 1 to 3; P = .013), ISCC (International Federation of Gynecology and Obstetrics stages I to IV; P = .001), and ADC ( P = .007). An overall significant mean difference was observed between HES1, JAG1, and Notch-3 proteins in precancer ( P = .001), ISCC ( P = .001), and ADC ( P = .001). Pairwise comparisons between HES1 and JAG1 and HES1 and Notch-3 were also found to be significant. CONCLUSION This study showed that among all HPV-16–positive precancers, the major HES1 positivity signal arises from cervical intraepithelial neoplasia grades 2 and 3 that develops into ISCC. Moreover, HPV-16–positive ADC also showed an association with HES1. The HES1, JAG1, and Notch-3 proteins showed their synergistic role in modulating HPV associated ADC along with histologic subtypes of precancer and ISCC of CC.

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

2009 ◽  
Vol 127 (3) ◽  
pp. 122-127 ◽  
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.

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

2013 ◽  
Vol 23 (3) ◽  
pp. 500-506 ◽  
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.

scholarly journals Prevalence and distribution of human papillomavirus genotypes in cervical intraepithelial neoplasia in China: a meta-analysis

2020 ◽  
Vol 302 (6) ◽  
pp. 1329-1337
Author(s):  
Junya Zhang ◽  
Keyan Cheng ◽  
Zhilian Wang
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Infection Rate ◽  
Meta Analysis ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Screening Tests ◽  
Cochrane Library ◽  
Hpv Vaccines ◽  
Hpv Genotypes

Abstract Background and aim Data on type-specific human papillomavirus (HPV) are needed to investigate HPV-based screening tests and HPV vaccines. However, Chinese relevant data are insufficient. Therefore, this meta-analysis aimed to summarize and demonstrate the prevalence and distribution of HPV genotypes in cervical intraepithelial neoplasia (CIN) and compensate for the shortage of HPV vaccines in China. Methods The Medline, Embase, and the Cochrane Library databases, as well as references cited in the selected studies, were systematically searched for studies investigating the prevalence and distribution of HPV genotypes between January 2000 and April 2019 in China. Results A total of 8 studies were identified, which comprised 2950 patients with CIN1 and 5393 with CIN2/3. The overall HPV infection rate was 84.37%. The HPV infection rate was significantly higher in the CIN2/3 group (87.00%) than in the CIN1 group (79.56%) (χ2 = 80.095, P < 0.001). The most common HPV types in CIN1 in order of decreasing prevalence were as follows: HPV52 (20.31%), HPV16 (16.81%), HPV58 (14.44%), HPV18 (6.44%), and HPV53 (5.76%). However, in the CIN2/3 group, HPV16 (45.69%) was the predominant type, followed by HPV58 (15.50%), HPV52 (11.74%), HPV33 (9.35%), and HPV31 (4.34%). Conclusions This study suggested that HPV16, HPV52, and HPV58 were the top three types of CIN in China. The findings might provide a reference for future HPV-based cervical cancer screening tests, treatment of HPV infection, and application of HPV vaccines in China.

Human Papillomavirus Typing and Viral Gene Expression Analysis for the Triage of Women With Abnormal Results From Papanicolaou Test Smears to Colposcopy

2009 ◽  
Vol 133 (10) ◽  
pp. 1577-1586 ◽  
Author(s):  
Nick A. Antonishyn ◽  
Greg B. Horsman ◽  
Rod A. Kelln ◽  
Alberto Severini
Keyword(s):  
Gene Expression ◽  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Diagnostic Methods ◽  
Screening Tools ◽  
Papanicolaou Test ◽  
Hpv 16 ◽  
Hpv E6 ◽  
Abnormal Results

Abstract Context.—A cascade of molecular tests for human papillomavirus (HPV), as a follow-up to Papanicolaou test screening, could eliminate unnecessary colposcopy. Tests based on detection of HPV E6 messenger RNA (mRNA) are already being used as screening tools, but there is a good biological rationale for expecting that an increase in the relative amounts of HPV E6 mRNA in cervical samples may better predict cancerous transformation. Objective.—To compare some of the available diagnostic methods and our novel method of relative quantification (RQ) of HPV gene expression for the effective triage of women with abnormal results from Papanicolaou tests to colposcopy. Design.—Sensitivities, specificities, and likelihood ratios were calculated for repeat Papanicolaou test smears, HPV DNA polymerase chain reactions, HPV genotyping, HPV-16 E6 mRNA detection, and the RQ of HPV-16 E6 mRNA calibrated to cellular RNA and DNA levels and standardized to viral load. Results.—Human papillomavirus genotype in combination with a repeat Papanicolaou test can be used to categorize most women (96%) with cervical intraepithelial neoplasia of grade 2 or higher for colposcopy while eliminating 44% of women with cervical intraepithelial neoplasia 1 or less. The presence of HPV-16 E6 mRNA (P &lt; .001) and RQ of HPV-16 E6 mRNA (P &lt; .001) displayed significant median differences among the various grades of cervical intraepithelial neoplasia. Further testing of women who are positive for HPV-16 demonstrated that the RQ of E6 mRNA has diagnostic potential when combined with Papanicolaou testing in populations with higher disease prevalence. Conclusions.—The RQ of HPV E6 mRNA and HPV genotype could be useful in a cascade of diagnostic testing designed to refer women with findings of cervical abnormalities for colposcopy or treatment while reducing triage numbers.

scholarly journals Role of Epstein-Barr Virus and Human Papillomavirus Coinfection in Cervical Intraepithelial Neoplasia in Chinese Women Living With HIV

2021 ◽  
Vol 11 ◽  
Author(s):  
Min Feng ◽  
Rufei Duan ◽  
Yang Gao ◽  
Han Zhang ◽  
Youlin Qiao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Epstein Barr Virus ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Barr Virus ◽  
Epstein Barr

Given that only a small percentage of human papillomavirus (HPV)-positive women develop cancer, HPV is necessary but insufficient for carcinogenesis. Mucosally transmitted viral cofactors appear to contribute to HPV-related cervical cancer, such as Epstein-Barr virus (EBV), but previous studies have shown inconsistent outcomes. The exact role of EBV in cervical cancer remains unclear, and more studies are needed to determine its involvement. In this study, we describe the prevalence of EBV and HPV coinfection in HIV-positive women and explore how abnormal host immune status induced by viral coinfections modulates epithelial gene expression. We found a significant correlation between EBV-HPV coinfection and the incidence of high-grade cervical intraepithelial neoplasia (CIN2+). RNA sequencing indicated that CIN tissues coinfected with EBV and HPV led to significant changes in the gene expression of epithelial differentiation and development compared to normal tissues with HPV infection alone. In particular, several differentially expressed genes (DEGs) are closely associated with cancer, such as CACNG4, which was confirmed to be upregulated at both the mRNA and protein levels. Therefore, these findings provide some evidence that EBV may act as a cofactor or mediator in HPV-related cervical cancer. Specific genes or proteins, such as CACNG4, may serve as biomarkers that can risk stratify patients based on pathological changes in the cervix.

PECULIARITIES OF PAPILLOMAVIRUS GENOTYPING IN PATIENTS WITH CERVICAL INTRAEPITHELIAL NEOPLASIA

2020 ◽  
pp. 104-111
Author(s):  
N.A. Shmakova ◽  
G.N. Chistyakova ◽  
I.N. Kononova ◽  
I.I. Remizova
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Viral Load ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Squamous Intraepithelial Lesions ◽  
Hpv 16 ◽  
The World ◽  
Intraepithelial Lesions ◽  
Hpv 18

Recently, there has been a steady growth of cervical cancer all over the world, especially in Russia. Patients with cervical cancer have become much younger. At the same time, the human papillomavirus is not only the main factor in the neoplastic process, but it is also one of the most common sexually transmitted infections in the world. The aim of the paper is to assess the prevalence and characteristics of human papillomavirus genotypes in patients with cervical intraepithelial neoplasia. Materials and Methods. During the periodic screening we examined 213 women of a reproductive age with HPV infection. All patients underwent liquid-based cytology and human papillomavirus genotyping by polymerase chain reaction. Results. We revealed that the prevalence of cervical intraepithelial neoplasia among women with papillomavirus infection was 80.3 % (n=171). According to human papillomavirus genotyping, HPV 16 (38 %) and HPV 33 (32 %) prevailed. We also observed positive high correlation between high-grade squamous intraepithelial lesions (HSIL) and HPV 18 (r=+0.759, p=0.001), a negative mean correlation between HPV 45 and low-grade squamous intraepithelial lesions (LSIL) (r=-0.643, p=0.002). A cohort of patients with severe intraepithelial cervical lesions demonstrated high viral load rates. Conclusion. According to the results obtained, we established the dominance of HPV 16 and HPV 33 genotypes in cervical intraepithelial neoplasia. There were significant differences between HSIL and LSIL patients with HPV 18 and HPV 45. There was also a correlation between an increase in the viral load with the severity of the pathological process. Keywords: human papillomavirus, intraepithelial cervical neoplasms, cervical cancer. В последние годы в мире, особенно в России, наблюдается неуклонный рост и «омолаживание» рака шейки матки. При этом вирус папилломы человека является не только основным фактором прогрессирования неопластического процесса, но и одной из наиболее распространенных инфекций, предаваемых половым путем, в мире. Цель. Оценить распространенность и характеристику генотипов папилломавирусной инфекции у пациенток с цервикальными интраэпителиальными неоплазиями. Материалы и методы. Проведено обследование 213 пациенток репродуктивного возраста с ВПЧ-инфекцией, пришедших на профилактический осмотр. Всем женщинам было выполнено цитологическое исследование жидкостным методом и генотипирование вируса папилломы человека методом полимеразной цепной реакции. Результаты. Распространенность цервикальных интраэпителиальных неоплазий среди женщин с папилломавирусной инфекцией составила 80,3 % (171 пациентка). Согласно данным генотипирования вируса папилломы человека превалировал 16-й (38 %) и 33-й типы (32 %). Выявлена положительная высокая корреляционная связь между цервикальными неоплазиями высокой степени онкогенного риска (HSIL) и 18-м типом ВПЧ-инфекции (r=+0,759 при р=0,001), отрицательная средняя корреляционная связь 45-го типа ВПЧ с низкой степенью онкогенного риска (LSIL) (r=-0,643 при р=0,002). Продемонстрированы высокие показатели вирусной нагрузки в когорте пациенток с тяжелыми внутриэпителиальными цервикальными поражениями. Выводы. По результатам полученных данных установлено доминирование 16-го и 33-го генотипов ВПЧ при цервикальных интраэпителиальных неоплазиях с наличием значимых различий между пациентами с HSIL и LSIL в отношении 18-го и 45-го типов, а также связь роста уровня вирусной нагрузки с увеличением степени тяжести патологического процесса. Ключевые слова: вирус папилломы человека, интраэпителиальные новообразования шейки матки, рак шейки матки.

scholarly journals Ten-year follow-up of human papillomavirus vaccine efficacy against the most stringent cervical neoplasia end-point—registry-based follow-up ofthree cohorts from randomized trials

BMJ Open ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. e015867 ◽  
Author(s):  
Matti Lehtinen ◽  
Camilla Lagheden ◽  
Tapio Luostarinen ◽  
Tiina Eriksson ◽  
Dan Apter ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Cancer Registry ◽  
Vaccine Efficacy ◽  
Invasive Cervical Cancer ◽  
Intraepithelial Neoplasia ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Hpv 16 ◽  
Link Type

ObjectiveDue to long lag time between infection/cancer diagnoses human papillomavirus (HPV) vaccination programs will deliver vaccine efficacy (VE) estimates against cancer end-points late. Cancer registry follow-up of population-based, randomised trial cohorts of vaccinated and unvaccinated women was undertaken for the estimation of VE against cervical intraepithelial neoplasia grade three and invasive cancer (CIN3+).MethodsWe report interim results with 98 561 person years of Finnish Cancer Registry -based follow-up of individually and/or cluster randomised cohorts of HPV-16/18 vaccinated and unvaccinated adolescent women enrolled in June 2003/2005, and between May 2004 and April 2005, respectively. The cohorts comprised 15 627 18- to 19-year-old unvaccinated women (NCT01393470), and 2 401 and 64 16- to 17-year-old HPV-16/18 vaccinated women participating the PATRICIA (NCT00122681) and HPV-012 (NCT00169494) trials, respectively. The age-aligned passive follow-up started 6 months after the clinical trials’ end.ResultsDuring the follow-up of 4.5 to 10 years post enrolment we identified 75 cases of cervical intraepithelial neoplasia grade 3 (CIN3) and 4 cases of invasive cervical cancer (ICC) in the unvaccinated cohort, and 4 CIN3 cases in the HPV-16/18 vaccinated women. Diagnostic blocks were available for HPV typing from 87% of the cases. CIN3+ lesions were detectable in 54 cases. HPV16 was found in 26 of 50 unvaccinated CIN3+ cases, and in 3 CIN3+ cases in the HPV-16/18 vaccinated women. The latter were all baseline positive for cervical HPV16 DNA. Baseline data was not available for the unvaccinated women. Intention-to-treat VE against any CIN3+ was 66% (95% CI 8, 88).ConclusionsTen years post vaccination the AS04-adjuvanted HPV-16/18 vaccine shows continued efficacy against CIN3+ irrespectively of HPV type. Vaccine efficacy was not observed in baseline HPV16 DNA positive subjects.Trial registration numberNCT01393470.

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