Carcinogenic Human Papillomavirus Research Articles

Targeted Next Generation Sequencing for Human Papillomavirus Genotyping in Cervical Liquid-Based Cytology Samples.

Simple SummaryTesting for Human Papillomavirus (HPV) is currently being implemented as part of cervical cancer (CC) screening in several countries. However, infections with all but one of the HPV types classified as possibly carcinogenic cannot be detected by the assays used for CC screening today. The aim of our study was to demonstrate the use of a targeted next generation sequencing (NGS) HPV panel for CC screening—both general practitioner-collected samples and self-samples. We here show that the targeted HPV panel can detect HPV with a sensitivity and specificity similar to commercial HPV assays, one of which is used for CC screening today. However, the targeted HPV panel possess several advantages compared to the screening assays, as it enables specific detection of all relevant HPV types and can identify viral integration, variants in the HPV genome, and dominant HPV types in multi-infected cases.At present, human papillomavirus (HPV) testing is replacing morphology-based cytology as the primary tool for cervical cancer screening in several countries. However, the HPV assays approved for screening lack detection for all but one of the possibly carcinogenic HPV types and do not genotype all included HPV types. This study demonstrates the use of a targeted HPV next generation sequencing (NGS) panel to detect and genotype all 25 carcinogenic, probably carcinogenic, and possibly carcinogenic HPV types as well as the low-risk types HPV6 and HPV11. The panel was validated using a cohort of 93 paired liquid-based cytology samples (general practitioner (GP)-collected cervical samples and cervico-vaginal self-samples (SS)). Overall, the targeted panel had a sensitivity (GP = 97.7%, SS = 92.1%) and specificity (GP = 98.0%, SS = 96.4%) similar to the commercial HPV assays, Cobas® 4800 HPV DNA test (Roche) and CLART® HPV4S assay (GENOMICA). Interestingly, of the samples that tested positive with the NGS panel, three (6.4%) of the GP-collected samples and four (9.1%) of the self-samples tested positive exclusively for HPV types only included in the NGS panel. Thus, targeted HPV sequencing has great potential to improve the HPV screening programs since, as shown here, it can identify additional HPV positive cases, cases with HPV integration, variants in the HPV genome, and which HPV type is dominant in multi-infected cases.

Prevalence and Distribution of Human Papillomavirus Genotypes (1997-2019) and Their Association With Cervical Cancer and Precursor Lesions in Women From Southern Mexico.

BackgroundCervical cancer (CC) is the fourth most common malignancy of the female genital tract. Human Papillomavirus (HPV) is the main cause of precancerous lesions and CC cases worldwideObjectiveWe assessed the prevalence and distribution of HPV types and their association with precancerous lesions and CC.MethodsHPV genotypes were detected by 3 methods depending on the year of in which the sample was analyzed: MY09/11 RFLPs (1997 to 2010), GP5+/6+ primer systems (2005 to 2010) and INNO-LiPA HPV Genotyping Extra (2010 to 2019) in cervical samples (No-IL: 4445; LSIL: 2464; HSILs: 151 and CC: 253) from women from southern Mexico.ResultsThe overall HPV prevalence was 54.17%, and hpv-16 was the most common genotype. In single infection, the high-risk HPV genotypes (group 1) were associated with squamous intraepitelial lesions (LSIL: HPV–39 (OR = 10.58, 95% CI 4.09–27.36, P < .001); HSIL: HPV-31 (OR = 14.76, 95% CI 6.56–33.20, P < .001); and CC: HPV-16 (OR = 25.01, 95% CI 18.83–33.21, P < .001). In multiple infections, the HPV genotypes (HPV-16 and HPV-18) were also associated with a high risk of lesions [LSIL: HPV-18 (OR = 3.45; 95% CI 1.36–8.91; P = .009); HSIL: HPV-18 (OR = 5.12; 95% CI 1.21–21.68; P = .026); and CC: HPV-16 (OR = 3.03; 95% CI 1.72–5.32; P < .001)] compared to single infection. In the analysis adjusted for age, giving birth, and cigarette smoking, a significant increase in the risk of LSIL, HSIL, and CC was maintained.ConclusionsThis study provides current data on the prevalence and distribution of HPV genotypes in women from southern Mexico, which could serve as a valuable reference to guide nationwide CC screening programs and provide scientific evidence that could be useful for vaccine development efforts. Likewise, it was identified that infection with carcinogenic HPV genotypes is an independent risk factor for LSIL, HSIL, and CC.

Trend of HPV 16/18 Genotypes in Cervical Intraepithelial Neoplasia Grade 3: Data for 2007-2018.

AimIn the post-vaccination era, the starting age and time intervals of cervical screening could change (older age and longer screening intervals). This scenario may be achieved by significantly reducing human papillomavirus (HPV) 16/18 prevalence (genotypes included in the current vaccines). In this regard, assessing the trend over time of these HPV infections in high-grade cervical lesions can provide information on the objective. The present study aimed to evaluate the trend of HPV 16/18 over the years 2007–2018 in women with cervical intraepithelial neoplasia (CIN) grade 3.MethodsThis is a retrospective multi-institutional study including HPV genotyped and unvaccinated women under 30 with CIN3. The sample was divided into the following periods: 2007–2010, 2011–2014, 2015–2018. HPV genotypes were grouped in genotypes 16/18, genotypes 31/33/35/52/58/67 (genetically related to HPV16), genotypes 39/45/59/68/70 (genetically related to HPV18), genotypes 31/33/45/52/58 (high-risk types included in the nonavalent vaccine), possibly carcinogenic HPV (genotypes 26/30/53/67/70/73/82/85), low-risk HPV (genotypes 6/11/40/42/43/44/54/55/61). The trend between periods and HPV genotypes was measured using the Cochran–Armitage test for trend.ResultsThe final analysis included 474 participants. HPV 16/18 prevalence decreased significantly over the years (77.8% vs 68.9% vs 66.0%, respectively, Ptrend=0.027). Possibly carcinogenic HPV (genotypes 26/30/53/67/70/73/82/85) showed a significant negative prevalence trend over time (4.9% vs 1.1% vs 1.3%, respectively, Ptrend=0.046). Finally, there was a significant positive trend over the years for high-risk HPV genotypes 31/33/45/52/58 in women under 25 (9.9% vs 17.0% vs 24.0%, respectively, Ptrend=0.048).ConclusionThe prevalence of CIN3 lesions related to HPV 16/18 genotypes decreased over time from 2007 to 2018. These data highlight a herd effect of the HPV vaccine. However, fifteen years after HPV vaccine introduction, we are still a long way from herd immunity. The increase in high-risk types 31/33/45/52/58 will need to be reassessed when the nonavalent vaccine impact will be more reliable.

Prevalent human papillomavirus infection increases the risk of HIV acquisition in African women: advancing the argument for human papillomavirus immunization.

Vaccine-preventable human papillomavirus (HPV) infection is common, especially in sub-Saharan Africa where HIV risk is also high. However, unlike other sexually transmitted infections (STIs), HPV's role in HIV acquisition is unclear. We evaluated this relationship using data from MTN-003, a clinical trial of HIV chemoprophylaxis among cisgender women in sub-Saharan Africa. A case-control study. We matched 138 women who acquired HIV (cases) to 412 HIV-negative controls. Cervicovaginal swabs collected within 6 months before HIV seroconversion were tested for HPV DNA. We estimated the associations between carcinogenic (high-risk) and low-risk HPV types and types targeted by HPV vaccines and HIV acquisition, using conditional logistic regression models adjusted for time-varying sexual behaviors and other STIs. Mean age was 23 (±4) years. Any, high-risk and low-risk HPV was detected in 84, 74 and 66% of cases, and 65, 55 and 48% of controls. Infection with at least two HPV types was common in cases (67%) and controls (49%), as was infection with nonavalent vaccine-targeted types (60 and 42%). HIV acquisition increased with any [adjusted odds ratio (aOR) 2.5, 95% confidence interval (95% CI) 1.3-4.7], high-risk (aOR 2.6, 95% CI 1.5-4.6) and low-risk (aOR 1.8, 95% CI 1.1-2.9) HPV. Each additional type detected increased HIV risk by 20% (aOR 1.2, 95% CI 1.1-1.4). HIV acquisition was associated with HPV types targeted by the nonavalent (aOR 2.1, 95% CI 1.3-3.6) and quadrivalent vaccines (aOR 1.9, 95% CI 1.1-3.2). HPV infection is associated with HIV acquisition in sub-Saharan African women. In addition to preventing HPV-associated cancers, increasing HPV vaccination coverage could potentially reduce HIV incidence.

Human papilloma viruses infection among adolescent females perinatally infected with HIV in Côte d’Ivoire

BackgroundCervical cancer prevention strategies recommend human papilloma virus (HPV) vaccination for female adolescents prior to their sexual debut. While HIV is a major risk factor for HPV infection in women...

A proposed new generation of evidence-based microsimulation models to inform global control of cervical cancer

Health decision models are the only available tools designed to consider the lifetime natural history of human papillomavirus (HPV) infection and pathogenesis of cervical cancer, and the estimated long-term impact of preventive interventions. Yet health decision modeling results are often considered a lesser form of scientific evidence due to the inherent needs to rely on imperfect data and make numerous assumptions and extrapolations regarding complex processes. We propose a new health decision modeling framework that de-emphasizes cytologic-colposcopic-histologic diagnoses due to their subjectivity and lack of reproducibility, relying instead on HPV type and duration of infection as the major determinants of subsequent transition probabilities. We posit that the new model health states (normal, carcinogenic HPV infection, precancer, cancer) and corollary transitions are universal, but that the probabilities of transitioning between states may vary by population. Evidence for this variability in host response to HPV infections can be inferred from HPV prevalence patterns in different regions across the lifespan, and might be linked to different average population levels of immunologic control of HPV infections. By prioritizing direct estimation of model transition probabilities from longitudinal data (and limiting reliance on model-fitting techniques that may propagate error when applied to multiple transitions), we aim to reduce the number of assumptions for greater transparency and reliability. We propose this new microsimulation model for critique and discussion, hoping to contribute to models that maximally inform efficient strategies towards global cervical cancer elimination.

Relationship between the prevalence of oral human papillomavirus DNA and periodontal disease (Review).

Human papillomavirus (HPV) is a small DNA virus that infects the basal keratinocytes of squamous epithelium in the skin, and in the oral and genital mucosa. Smoking and sexual behavior have been recognized as significant risk factors for oral HPV infection. In the present review, the findings of recent studies of oral HPV infection in relation to periodontitis are discussed, as well as periodontopathic bacteria and periodontal herpes virus. Previous research suggests that HPV localizes to the inflammatory periodontal tissue. Inflammatory periodontal pockets may thus act as a reservoir for HPV. The interactions between HPV and periodontopathic bacteria remain unclear, but it is hypothesized that oral HPV infection may be related to a characteristic oral microbiome. Smoking is associated with HPV and periodontitis, as smoking induces destruction of periodontal tissue and suppresses the host defense, allowing HPV to infect periodontal tissue. Carcinogenic HPV and periodontitis may lead to the development of oral cavity cancer. However, oral HPV E6/E7 expression (transcriptionally active HPV) has not yet been fully investigated in patients with periodontitis. Collectively, the evidence suggests that oral HPV prevalence may be associated with periodontitis. The effect of clinical factors (age, sex, smoking, immunosuppressive condition and vaccination) on oral HPV DNA prevalence should be considered when clarifying the relationship between oral HPV and periodontitis. Additionally, the sampling method should be carefully chosen to directly detect HPV DNA in periodontal tissues.

Depiction of Vaginal Microbiota in Women With High-Risk Human Papillomavirus Infection.

Persistent infection with the carcinogenic human papillomavirus (HPV) is a prerequisite for the progression of cervical lesions and cancer. A growing body of research has focused on the functional role of the vaginal microbiota in the persistence of HPV infection. Understanding the microbial composition and structure in women with high-risk (hr)-HPV infection may help reveal associations between the vaginal microbiota and HPV infection, and identify potential biomarkers. Our study investigated the vaginal microbial community in women with and without hr-HPV infection, by using 16s rRNA gene sequencing. We found that microbial perturbations occurred in the early phase of hr-HPV infection. Lactobacillus and Sporolactobacillus were decreased, while bacteria related to bacterial vaginosis (BV), such as Gardnerella, Prevotella, Dialister, Slackia, Actinomyces, Porphyromonas, Peptoniphilus, Anaerococcus, Peptostreptococcus, Streptococcus, Ureaplasma, Megasphaera, and Mycoplasma were increased. Our results could offer insights into the correlations between hr-HPV and the vaginal microbiota in the early infection period, and provide indications that the predominance of some BV-associated bacteria during hr-HPV infection may increase the risk for cervical neoplasia.

PAPILLOMAVIRAL CARCINOGENESIS. SIGNIFICANT ACHIEVEMENTS AND SPECIFIC CHALLENGES. PART 3. THREE LEVELS OF CERVICAL CANCER PREVENTION AND TREATMENT

Efficient prophylactic vaccines have been developed to prevent cervical cancer, a frequent female oncological disease caused by carcinogenic human papillomaviruses. World Health Organization worked out the program for prophylaxis of cervical cancer and control of the disease. It includes preventive adolescent vaccinations, screening of precancerous cervical lesions in women as well as cervical cancer treatment if originated. Cervical cancer diagnostics is being improved, development of therapeutic human papillomaviruses vaccines is in progress. The review deals with major achievements and certain challenges in the field of cervical cancer prevention.Part I see: Volgareva G.M. Papillomaviral carcinogenesis. Major achievements and certain challenges. Part I. General notions of papillomaviruses. Human papillomavirusesassociated cancers. Russian Journal of Biotherapy 2020;19(1):6–12.Part 2 see: Volgareva G.M. Papillomaviral carcinogenesis. Major achievements and certain challenges. Part 2. HPV-associated cancers in Russia. Preventive HPV vaccines. Russian Journal of Biotherapy 2020;19(2):31–8.

Prevalence of human papilloma virus genotypes 16, 18 in women with abnormal cervical cytology smears (abnormal Pap smear) attending Erbil Maternity Teaching Hospital

Background and objective: Cervical cancer is the fourth most common cancer among women. Carcinogenic Human Papilloma Virus (HPV) infection is the major etiological agent for cervical cancer, of which70% are caused by HPV-16 and HPV-18 genotype infection. This study aimed to detect high risk HPV (16,18) in women with different abnormalities in pap smear to allow subsequent more accurate management of the cases and provide information that assists in future development of guidelines in our hospital. Methods: We performed a cross-sectional study on 100 ladies with an abnormal pap smear. Subjects were interviewed and underwent cervical testing with broom using liquid based samples to confirm the cytological abnormality and test for HPV genotypes 16 and 18 using Polymerase Chain Reaction (PCR). Then, colposcopy referral was done according to local protocols. Results: The median age of the subjects was 34. The prevalence of HPV genotypes 16,18 in the whole studied sample was 36%. Various studied risk factors showed significant association with abnormal pap smear and positive HPV genotypes 16,18, including the number of partners, increasing parity, age at first pregnancy, and smoking. Data were analyzed by the statistical package for the social sciences (version 23). Conclusion: The prevalence of HPV 16,18 was 36% in the sample, with the highest proportion being among those with high-grade lesions. Those using natural methods of contraception had higher rates of infection in comparison with other methods.

Assessment of women's knowledge about HPV vaccination in the light of the HPV infection as a risk factor for cervical cancer

Introduction Cervical cancer (CC) is one of the most prevalent malignancies of female reproductive tract. In Poland in 2017 CC accounted for 3.0% of all newly registered tumour cases among women, and was the eighth most common female malignancy. Persistent infection with carcinogenic human papillomavirus (HPV) is the leading risk facor. Currently, it is believed that infection with the human papillomavirus (HPV), especially its oncogenic types 16 and 18, is of fundamental importance in the development of cervical cancer. Vaccination prevents from infection with certain types of viruses, and consequently the development of cancer induced by a given type of virus. Therefore, their effi­cacy can be measured only in the long term, in a large cohort of vaccinated adolescents reaching the age charac­terized by the peak incidence of these cancers.Purpose The objective of the study was to evaluate knowledge about CC, as well as awareness of HPV and HPV vaccination among female respondents.Material and method The research was conducted on the group of 1,260 survey respondents, who filled out the Internet questionnaire. The obtained results were analysed and checked on the basis of scientific literature.Results The percentage of respondents who select human papillomavirus infection as a risk factor for the cervical cancer is 75.9%. The onset of intercourse at an early age was considered a risk factor by only 24.6%, while a large number of sexual partners by 45.4%. Women were also asked about knowledge of HPV vaccination. Only 73.8% of them heard about it and 26.2% declare unawarness of this type of vaccination.Conclusions Health promotion campaigns and educational programs are necessary in order to reduce cervical cancer burden and should be directed particularly towards those who have demonstrated low cervical cancer knowledge and low awareness regarding HPV and its vaccine.

Knowledge about Cervical Cancer and Awareness of Human Papillomavirus (HPV) and HPV Vaccine among Female Students from Serbia.

Background and objectives: Persistent infection with carcinogenic human papillomavirus (HPV) is the leading cause of cervical cancer. The study explored students’ knowledge about cervical cancer and awareness of human papillomavirus and the HPV vaccine. Materials and Methods: A questionnaire-based survey was carried out among 1616 first-year female college students at the University of Niš. It examined socio-demographic characteristics, measured the score of knowledge about cervical cancer, assessed awareness regarding HPV and the HPV vaccine and inquired about the source of information about cervical cancer and HPV. Results: The average cervical cancer knowledge score was 16.35 ± 7.92 (min 0, max 30), with medical professional education, parents’ education level, place of residence and relationship status having significant effects on the score. The awareness about HPV and the HPV vaccine was low, with only 14.2% of students having heard about both HPV and its vaccine. The most commonly reported sources of information were the media, while the most competent one was organized health education. Conclusions: Health promotion campaigns and educational programs are necessary in order to reduce cervical cancer burden and should be directed particularly towards those who have demonstrated low cervical cancer knowledge and low awareness regarding HPV and its vaccine.

Epidemiology and persistence of cervical human papillomavirus infection among outpatient women in Heilongjiang province: A retrospective cohort study.

As persistent carcinogenic human papillomavirus (HPV) infection is a prominent driver of cervical cancer, it is essential to explore HPV persistence and its associated factors for cancer screening and prevention. A retrospective cohort study was performed in outpatient women between March 2010 and 2019 in Heilongjiang, northeast China. HPV genotyping was performed by polymerase chain reaction-membrane hybridization. An unconditional logistic regression model was used to analyze the association of factors with persistence. The overall prevalence of HPV at baseline was 27.1%, with a downward trend from 2010 to 2019 (P < .0001). The most commonly observed high- and low-risk HPVs were HPV16 (N = 1094, 5.9%) and HPV11 (N = 596, 3.2%), respectively. The probabilities of 6-month persistence were high for women infected with HPV16 (P = .0001), HPV58 (P = .018), and HPV53 (P = .014), as well as for women with multiple infections (P = .009), and those who were 51 to 60 years old (P = .004) or more than 60 years old (P = .007). The probabilities of 12-month persistence were high for women infected with HPV53 (P = .017) and 51- to 60-year-old women (P = .044). HPV16 is the dominant HPV type in Heilongjiang. An age in the range of 51 to 60 years and infection with HPV53 is associated with HPV infection persistence in the Heilongjiang population.

Digital squamous cell carcinoma associated with possibly carcinogenic human papillomavirus type 73 (HPV73): a case report

We present a case report of a 64-year-old female patient with a 5-year history of a digital papule that clinically mimicked a common wart but was histologically diagnosed as digital squamous cell carcinoma (DSCC), a rare malignant cutaneous entity etiologically associated with high-risk human papillomaviruses (HR HPVs). This DSCC was positive for HPV73, which is currently classified under possible human carcinogens and has already been identified in DSCCs. Treatment with electrocoagulation and subsequent total excision with safety margins was successful, and no recurrence was detected during 6 years of follow-up. Analogously to cervical and other anogenital carcinomas, we assume that the incidence of DSCC will significantly decrease in the near future due to the widespread use of effective prophylactic HPV vaccines, which cover the majority of HR HPV types also associated with DSCC. However, HPV73 and other possibly carcinogenic and HR HPV types (as classified per the International Agency for Research on Cancer), which are not included in current prophylactic measures, will cause some portion of HPV-associated neoplasms, but this portion will be very minor.

Current Perspectives in Human Papilloma Virus: Where We are and What We Need?

It is now well-established that Human Papilloma Viruses (HPV) are responsible for causing &gt;90% of cervical cancers. Existing evidences have also demonstrated a key role for HPV in a portion of Head and Neck cancers as well as carcinomas of Vulva, Vagina, Penis and Anus. Therefore studies aiming at developing highly sensitive diagnostic methods have become high-priority in the recent years. To date, an estimated 202 types of HPV have been identified, of which only a small percentage viruses are involved in carcinogenesis. Among the carcinogenic HPV, the most predominant ones are HPV 16 and HPV 18. The other high risk types are 31, 33, 34, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, and 70. In general, HPV is detected by polymerase chain reaction (PCR) and hybrid capture (HC) methods. However, the existing PCR methods specifically identify only HPV 16 and HPV 18, but not the other types. More over, the PCR protocols are known for errors, and are not suitable for on-field screening procedures, hence, a suitable much quicker and sensitive method is required at the earliest. More over, the PCR and HC methods are expensive, hence, require more funds to conduct public health screening campaigns. Therefore, in this book chapter we have made an attempt to address the recent developments in HPV screening methods, and covered various advanced procedures available in the literature to identify HPV in patient specimens. For example, a section is dedicated to cover the “Biosensors”, which have been developed in detecting the HPV DNA in body fluids. These devices are much simpler compared to sequencing technologies and likely to be the next-generation detection devices for HPV

DNA demethylation agent 5azadC downregulates HPV16 E6 expression in cervical cancer cell lines independently of TBX2 expression.

HPV16 is the most carcinogenic human papillomavirus and causes >50% of cervical cancers, the majority of anal cancers and 30% of oropharyngeal squamous cell carcinomas. HPV carcinogenesis relies on the continuous expression of the two main viral oncoproteins E6 and E7 that target >150 cellular proteins. Among them, epigenetic modifiers, including DNA Methyl Transferases (DNMT), are dysregulated, promoting an aberrant methylation pattern in HPV-positive cancer cells. It has been previously reported that the treatment of HPV-positive cervical cancer cells with DNMT inhibitor 5-aza-2'-deoxycytidine (5azadC) caused the downregulation of E6 expression due to mRNA destabilization that was mediated by miR-375. Recently, the T-box transcription factor 2 (TBX2) has been demonstrated to repress HPV LCR activity. In the current study, the role of TBX2 in E6 repression was investigated in HPV16 cervical cancer cell lines following 5azadC treatment. A decrease of E6 expression was accompanied by p53 and p21 restoration. While TBX2 mRNA was upregulated in 5azadC-treated SiHa and Ca Ski cells, TBX2 protein was not detectable. Furthermore, the overexpression of TBX2 protein in cervical cancer cells did not allow the repression of E6 expression. The TBX2 transcription factor is therefore unlikely to be associated with the repression of E6 following 5azadC treatment of SiHa and Ca Ski cells.

Effectiveness of bivalent and quadrivalent human papillomavirus vaccination in Luxembourg

BackgroundIn Luxembourg, the human papillomavirus (HPV) vaccination program introduced in 2008, provided either bivalent (BV) or quadrivalent (QV) vaccines to girls aged 12–17 years. Here, we estimate the effectiveness of BV and QV vaccines combined and separately in reducing type-specific HPV prevalence eight years after the introduction of the vaccination program. MethodsA cross-sectional prevalence study was conducted among women aged 18–29 years in 2015-2017. Seven hundred sixteen participants were recruited at family planning centres or private gynaecology practices in Luxembourg. Vaccination records were verified in the social security database. Cervical samples were tested using the Anyplex II HPV28 assay. Vaccine effectiveness was estimated using logistic regression. ResultsIn total, 363/716 (50.7%) participants were HPV positive with any HPV and 209/716 (29.2%) with carcinogenic HPV genotypes. HPV vaccination offered high protection against HPV16/18 (adjusted odds ratio (AOR) = 0.13; 95% CI 0.03-0.63), HPV6/11 (AOR = 0.16; 95% CI 0.05-0.48) and cross-protection against HPV31/33/45 (AOR = 0.41; 95% CI 0.18-0.94). The AORs were generally enhanced when only considering vaccination before sexual debut corresponding to AORs: 0.05 (95% CI 0.00-0.88), 0.08 (95% CI 0.02-0.36) and 0.20 (0.06-0.65) against HPV16/18, HPV6/11 and HPV31/33/45, respectively. We observed significant protection against carcinogenic genotypes included in nonavalent vaccine for BV (AOR = 0.29; 95% CI 0.13-0.67), but not for QV (AOR = 0.81; 95% CI 0.47–1.40) (heterogeneity Chi2 P = 0.04). ConclusionsOur study suggests high effectiveness of HPV vaccination against HPV6/11, HPV16/18 and a cross-protection against HPV31/33/45. Vaccination effectiveness was slightly higher for women vaccinated before sexual debut.

Characteristics of carcinogenic HPV genotypes in North China Plain and the association with cervical lesions.

Human papillomavirus (HPV) infection is a crucial health problem and caused substantial malignancy diseases among female worldwide. We aim to investigate the distribution of HPV subtype and the status of cervical cancer and precancerous lesions caused by HPV infection in North China Plain population. A total of 61,870 samples of outpatients and inpatients from January 2015 to May 2017 at the Affiliated Hospital of Jining Medical University were collected. All of the samples were tested by rapid flow-through hybridization HPV genotyping. Approximately 17,280 of the cases tested positive for HPV, indicating an infection rate of 27.9%. Approximately 7009 cases were compared to the results of cytological diagnosis. The top five HPV genotypes were HPV-16 (4.5%), HPV-52 (2.9%), HPV-58 (2.8%), HPV-53 (1.9%), and HPV-81 (1.9%). The youngest age group (age < 20 years) showed the highest infection rate (59.9%), and then decreased with age. As the degree of cervical lesions worsened gradually, the rate of high-risk HPV infection increased, such as 24.3% (322/1324) in the Cervicitis, 31.30% (560/1785) in the CINI, 54.1% (568/1050) in the CINII, 80.1% (693/865) in the CIN III, and 99.5% (428/430) in the cervical cancer group. These findings were significantly different from the 9.7% (155/1555) observed in the normal medical examination group (P < .05). This is the first study to demonstrate the characteristics of HPV and the association with cervical lesions in North China Plain population.

Clustering patterns of type‐type combination in multiple genotypes infections of human papillomavirus in cervical adenocarcinoma

Coinfections with multiple types of human papillomavirus (HPV) occur in cervical adenocarcinoma (ADC). However, it remains unclear the clustering patterns of multiple types in HPV coinfections and relevant factors in ADC. A total of 718 paraffin-embedded ADC specimens were collected in China and tested for HPV genotypes using SPF10-INNO-LIPA. The prevalence of HPV coinfections and clustering patterns by geographical regions, histological subtypes and ages were assessed. Type-specific attribution of HPV to ADC adjusted by HPV coinfections were calculated. The prevalence of HPV coinfections was found to be 8.4% in ADC cases with slight variation by geographic regions between 2.2% and 12.5%. The 88.3% of all HPV multiple infections in ADC were two types of HPV coinfections with predominant combination of HPV 16 and HPV 18. The attribution to ADC was 88.0% for HPV 16/18 targeted by bivalent and quadrivalent vaccine and 96.8% for HPV 16/18/31/33/45/52/58 targeted by nonavalent vaccine. Clustering patterns of multiple types were related with histological categories and age at diagnosis. In conclusion, HPV coinfections are uncommonly prevalent in ADC cases with slight variation by geographic regions and distinct clustering patterns of multiple types by histological subtypes and ages at diagnosis. The high attribution of carcinogenic HPV types to ADC predicts potential protection of HPV vaccine against ADC.

Thin variant of high-grade squamous intraepithelial lesion - relationship with high-risk and possibly carcinogenic human papilloma virus subtypes and somatic cancer gene mutations.

AimTo further characterise the thin variant of high‐grade squamous intraepithelial lesions (HSILs) of the cervix defined by the World Health Organization as full‐thickness HSILs with nine or fewer cell layers.Methods and resultsWe examined 31 excisional cervical specimens featuring exclusively p16INK4a‐overexpressing thin HSILs with respect to size, location at the squamocolumnar junction or endocervical mucosa, human papilloma virus (HPV) subtypes (pretherapeutic clinical HPV tests and HPV genotyping on lesional tissue after excision), and somatic mutations in 50 cancer genes. Thin HSILs were typically solitary lesions, located at the squamocolumnar junction (20/31; 65%), in the endocervical columnar epithelium (6/31; 19%), and in both locations (5/31; 16%). The horizontal extension of thin HSILs ranged from 100 µm to 8 mm, with 30% being <1 mm. HPV data were available for 27 specimens. Twenty of 27 (74%) thin HSILs showed high‐risk HPV subtypes: HPV16 (n = 8), HPV16 with coinfection (n = 2), HPV18 (n = 1), HPV31 (n = 1), HPV33 (n = 2), HPV52/58 (n = 2), and ‘other’ high‐risk HPV genotypes (n = 4). Five of 27 (19%) thin HSILs showed possibly carcinogenic subtypes: HPV53 (n = 3), HPV73 (n = 1), and HPV82 (n = 1). One thin HSIL was induced by low‐risk HPV6 and one by the unclassified subtype HPV44. Somatic gene mutations were not identified.ConclusionThin HSILs were typically small lesions without somatic gene mutations. Two‐thirds of thin HSILs developed after a transforming infection with high‐risk HPV subtypes, and one‐third were induced by non‐high‐risk HPV subtypes. If cervical cancer screening relies solely on presently available clinical HPV DNA tests, a significant percentage of women with HSIL will be missed.