Human Papillomavirus Genotypes Research Articles

Vaginal flora in HPV infection: a cross‑sectional analysis

Objective The vaginal flora has been reported to be associated with human papillomavirus (HPV) infection. The purpose of this study was to investigate the characteristics of the cervical microbiota in patients with HPV infection and to analyse the changes in the vaginal flora and enzyme profiles in females with HPV infection. Methods We conducted a cross-sectional study involving 206 participants who underwent HPV genotyping, sexually transmitted diseases pathogen testing, cytology examination, and microbiome analysis. Additionally, we collected 115 HPV-negative samples and 48 HPV-positive samples for 16S rRNA amplicon sequencing. The vaginal microbial communities of both groups were analysed for diversity and differences to explore their association with HPV infection. Results The abundance of Lactobacillus was found to be reduced, while Gardnerella vaginalis was significantly more prevalent in the HPV + group. In terms of alpha diversity indices, the Shannon index (P = .0036) and Simpson index (P = .02) were higher in the HPV + group compared to the HPV − group, indicating greater community diversity in the HPV + group. Among the 10 sexually transmitted diseases pathogens analysed, Uup3 and Uup6 were significantly associated with HPV infection. Statistically significant differences were observed in Nugent scores and bacterial vaginosis between the two groups (P < .05). In functional analysis, 11 proteins and 13 enzymes were found to be significantly altered in the HPV + group. Conclusion Our study demonstrates that disruptions in the vaginal flora are associated with HPV infection. Reduced levels of Lactobacillus, increased prevalence of Gardnerella, and abnormal enzyme profiles are closely linked to HPV infection.

T-cell immunity induced and reshaped by an anti-HPV immuno-oncotherapeutic lentiviral vector

We recently developed an immuno-oncotherapy against human papillomavirus (HPV)-induced tumors based on a lentiviral vector encoding the Early E6 and E7 oncoproteins of HPV16 and HPV18 genotypes, namely “Lenti-HPV-07”. The robust and long-lasting anti-tumor efficacy of Lenti-HPV-07 is dependent on CD8+ T-cell induction and remodeling of the tumor microenvironment. Here, we first established that anti-vector immunity induced by Lenti-HPV-07 prime has no impact on the efficacy of a homologous boost to amplify anti-HPV T-cell immunity. To longitudinally monitor the evolution of the T-cell repertoire generated after the prime, homologous or heterologous boost with Lenti-HPV-07, we tracked T-cell clonotypes by deep sequencing of T-Cell Receptor (TCR) variable β and α chain mRNA, applied to whole peripheral blood cells (PBL) and a T cell population specific of an immunodominant E7HPV16 epitope. We observed a hyper-expansion of clonotypes post prime, accompanied by increased frequencies of HPV-07-specific T cells. Additionally, there was a notable diversification of clonotypes post boost in whole PBL, but not in the E7HPV16-specific T cells. We then demonstrated that the effector functions of such Lenti-HPV-07-induced T cells synergize with anti-checkpoint inhibitory treatments by systemic administration of anti-TIM3 or anti-NKG2A monoclonal antibodies. While Lenti-HPV-07 is about to enter a Phase I/IIa clinical trial, these results will help better elucidate its mode of action in immunotherapy against established HPV-mediated malignancies.

Impact of human papillomavirus types on uterine cervical neoplasia.

Human papillomavirus (HPV) is a major cause of cervical cancer. As the natural history of HPV-associated cervical lesions is HPV genotype-dependent, it is important to understand the characteristics of these genotypes and to manage them accordingly. Among high-risk HPVs, HPV16 and 18 are particularly aggressive, together accounting for 70% of HPV genotypes detected in cervical cancer. Other than HPV16 and 18, HPV31, 33, 35, 45, 52, and 58 are also at a high risk of progression to cervical intraepithelial neoplasia (CIN)3 or higher. Recent studies have shown that the natural history of HPV16, 18, 52, and 58, which are frequently detected in Japan, depends on the HPV genotype. For example, HPV16 tends to progress in a stepwise fashion from CIN1 to CIN3, while HPV52 and 58 are more likely to persist in the CIN1 to CIN2 state. Among the high-risk HPVs, HPV18 has some peculiar characteristics different from those of other high-risk HPV types; the detection rate in precancerous lesions is much lower than those of other high-risk HPVs, and it is frequently detected in highly malignant adenocarcinoma and small cell carcinoma. Recent findings demonstrate that HPV18 may be characterized by latent infection and carcinogenesis in stem cell-like cells. In this context, this review outlines the natural history of HPV-infected cervical lesions and the characteristics of each HPV genotype.

Differential long-term bivalent HPV vaccine cross-protection by variants in the Costa Rica HPV vaccine trial

The AS04-adjuvanted human papillomavirus (HPV)16/18 vaccine, an L1-based vaccine, provides strong vaccine efficacy (VE) against vaccine-targeted type infections, and partial cross-protection to phylogenetically-related types, which may be affected by variant-level heterogeneity. We compared VE against incident HPV31, 33, 35, and 45 detections between lineages and SNPs in the L1 region among 2846 HPV-vaccinated and 5465 HPV-unvaccinated women through 11-years of follow-up in the Costa Rica HPV Vaccine Trial. VE was lower against HPV31-lineage-B (VE=60.7%;95%CI = 23.4%,82.8%) compared to HPV31-lineage-A (VE=94.3%;95%CI = 83.7%,100.0%) (VE-ratio = 0.64;95%CI = 0.25,0.90). Differential VE was observed at several lineage-associated HPV31-L1-SNPs, including a nonsynonymous substitution at position 6372 on the FG-loop, an important neutralization domain. For HPV35, the only SNP-level difference was at position 5939 on the DE-loop, with significant VE against nucleotide-G (VE=65.0%;95%CI = 28.0,87.8) but not for more the common nucleotide-A (VE=7.4%;95%CI = −34.1,36.7). Because of the known heterogeneity in precancer/cancer risk across cross-protected HPV genotype variants by race and region, our results of differential variant-level AS04-adjuvanted HPV16/18 vaccine efficacy has global health implications.

The association between smoking and cervical human papillomavirus infection among women from indigenous communities in western Botswana

Introduction Cervical cancer, a malignancy caused by infection with oncogenic human papillomavirus, disproportionally affects women from low resource settings. Persistence of human papillomavirus infection may mediate an association between tobacco use and cervical cancer. In limited resource settings, women from indigenous communities are often marginalized and do not benefit from evidence-based interventions to prevent tobacco use or cervical cancer due to the limited reach of mainstream healthcare services to these communities. This study determined the association between smoking and high-risk human papillomavirus infection among women from indigenous communities in western Botswana. Methods A cross-sectional study of women in indigenous communities was conducted between June and October 2022. Demographic, clinical and self-reported smoking data were collected. Cervical cytology and HPV DNA testing for high-risk human papillomavirus genotypes were performed. Multilevel multivariable logistic regression models were fit to evaluate the association between smoking and high-risk human papillomavirus infection while adjusting for potential confounders. Results A total of 171 participants with a median (interquartile range) age of 40 (31–50) years from three settlements and two villages were recruited for the study. Of these, 17% were current smokers, 32.8% were living with HIV and high-risk human papillomavirus DNA was detected in 32.8% of the cervical specimens. Women who were current smokers, were nearly twice as likely to have cervical high-risk human papillomavirus infection compared to non-smokers (Adjusted Odds Ratio (95% CI); 1.74(1.09, 2.79)) after controlling for confounders. Conclusion These data underscore the need for effective tobacco control to help mitigate cervical cancer risk in this setting. These findings can help inform decisions about targeted cervical cancer prevention and tobacco cessation interventions for women from indigenous communities.

Decoding Fujian's cervical HPV landscape: unmasking dominance of non-16/18 HR-HPV and tailoring prevention strategies at a large scale.

Persistent HR-HPV causes cervical cancer, exhibiting geographic variance. Europe/Americas have higher HPV16/18 rates, while Asia/Africa predominantly have non-16/18 HR-HPV. This study in Fujian, Asia, explores non-16/18 HR-HPV infections, assessing their epidemiology and cervical lesion association for targeted prevention. A total of 101,621 women undergoing HPV screening at a hospital in Fujian Province from 2013 to 2019 were included. HPV genotyping was performed. A subset of 11,666 HPV-positive women with available histopathology results were analyzed to characterize HPV genotype distribution across cervical diagnoses. In 101,621 samples, 24.5% tested positive for HPV. Among these samples, 17.3% exhibited single infections, while 7.2% showed evidence of multiple infections. The predominant non-16/18 high-risk HPV types identified were HPV 52, 58, 53, 51, and 81. Single HPV infections accounted for 64.1% of all HPV-positive cases, with 71.4% of these being non-16/18 high-risk HPV infections. Age-related variations were observed in 11,666 HPV-positive patients with pathological results. Cancer patients were older. In the cancer group, HPV52 (21.8%) and HPV58 (18.6%) were the predominant types, followed by HPV33, HPV31, and HPV53. Compared to single HPV16/18 infection, non-16/18 HPV predominated in LSIL. Adjusted odds ratios (OR) for LSIL were elevated: multiple HPV16/18 (OR 2.18), multiple non-16/18 HR-HPV (OR 2.53), and multiple LR-HPV (OR 2.38). Notably, solitary HPV16/18 conferred higher odds for HSIL and cancer. Our large-scale analysis in Fujian Province highlights HPV 52, 58, 53, 51, and 81 as predominant non-16/18 HR-HPV types. Multiple HPV poses increased LSIL risks, while solitary HPV16/18 elevates HSIL and cancer odds. These findings stress tailored cervical cancer prevention, highlighting specific HPV impacts on lesion severity and guiding region-specific strategies for optimal screening in Asia, emphasizing ongoing surveillance in the vaccination era.

Management for persistent HPV infection and cervical lesions among women infected with HIV: a retrospective observational cohort study

BackgroundEarly diagnosis and treatment of HPV persistent infection and cervical intraepithelial neoplasia, which have yet to be thoroughly characterized in Guangxi, Southwestern China, are the key preventative measures for the development of cervical cancer in women, particularly in HIV-infected women.MethodsA retrospective study of 181 patients with HPV infection or cervical intraepithelial neoplasia who received surgical excision of lesions and were prospectively enrolled at the Fourth People’s Hospital of Nanning between January 2018 and February 2023 was performed. HPV-infected patients were divided into two subgroups: HIV-infected and HIV/HPV-coinfected patients and compare differences between these groups.ResultsHPV16, 18, 52, and 58 were the most prevalent HPV genotypes. High-risk HPV was significantly co-infected with multiple genotypes (P = 0.0332). HIV-infected women were predisposed to HPV infection (P < 0.0001), and the development of cervical cancer at a young age (P = 0.0336) compared to HIV-uninfected women and the loop electrosurgical excision procedure (P = 0.0480) is preferred for the treatment.ConclusionsHIV infection may increase HPV prevalence and lead to cervical cancer development at a young age. The loop electrosurgical excision procedure is an efficient evaluation and treatment strategy for HIV-infected women suffering from cervical intraepithelial neoplasia.

Factors Associated with HPV Genital Warts: A Self-Reported Cross-Sectional Study among Students and Staff of a Northern University in Nigeria.

The menace of human papillomavirus (HPV) infections among low- and middle-income countries with no access to a free HPV vaccine is a public health concern. HPV is one of the most common sexually transmitted infections (STIs) in Nigeria, while the most known types of HPV genotypes being transmitted are the high-risk HPV-16 and 18 genotypes. In this study, we explored the predictors of self-reported HPV infections and HPV genital warts infection among a population of students, non-academic staff, and academic staff of Ibrahim Badamasi Babangida (IBB) University located in Lapai, Nigeria. We also assessed their knowledge about HPV infections and genotypes, and sexual behaviors. An online cross-sectional study was conducted by setting up a structured questionnaire on Google Forms and it was distributed to the university community via Facebook and other social media platforms of the university. The form captured questions on HPV infection, and knowledge about HPV infection and genotypes, as well as the sexual health of the participants. All variables were described using frequencies and percentage distribution; chi-squared test statistics were used to explore the association between HPV infection (medical records of HPV infection) and the participants' profile, and a logistic regression analysis was performed to examine the factors associated with HPV genital warts infection among the population. This study reveals those participants between the ages of 26-40 years (81.3%) and those currently not in a sexually active relationship-single/divorced (26.4%)-who have self-reported having the HPV-16 and -18 genotypes. Moreover, participants between 26-40 years of age (OR: 0.45, 95%CI: 0.22-0.89) reported themselves to be carriers of HPV genital warts. Therefore, this study reveals the factors associated with HPV infection and genital warts peculiar to IBB university students and staff. Hence, we suggest the need for HPV awareness programs and free HPV vaccine availability at IBB university.

Prevalence of Carcinogenic Genotypes of HPV-Infected Women in a Ten-Year Period (2014-2023) in Vojvodina, Serbia.

Background and Objectives: Human papillomavirus (HPV) infection and its etiological role in the development of cervical cancer are well established. The cervical cancer mortality rate in Serbia is one of the highest among European countries, and this cancer is the second-leading cause of death in Serbian women aged from 15 to 44. Materials and Methods: This retrospective study was conducted at the Institute of Public Health of Vojvodina. A total of 10,062 cervical specimens from Serbian women were collected and HPV tested in ten years. The study patients were divided into five age groups. HPV genotype testing was performed using a commercial kit to detect 14 high-risk (HR) HPV genotypes. Additionally, cervix cytology data have been available for patients tested in 2022 and 2023. Results: An overall positive rate was found in 43.3% of patients (4356/10,062). A single HPV infection (62.1%) was the main infection pattern. The most frequent HR HPV genotypes were HPV 16, 31, 52, 56, 39, and 51, comprising 62.3% of the detected genotypes, including multiple infections. A significant difference was noted in the HPV prevalence across the different age groups, with a bimodal distribution of HPV infection. The highest prevalence was recorded in the age group ≤ 30 and those after 61 years. Women diagnosed with high-grade squamous intraepithelial lesions (HSIL) were significantly older compared to others. HR HPV is the most prevalent in patients with HSIL cytological findings (76.5%). The most common type, according to age-specific distribution and cytological findings, was HR HPV 16. Conclusions: This study provides comprehensive data on HR HPV distribution among Serbian women, which can serve as a basis for subsequent monitoring of genotypic distribution. It is particularly significant considering they are missing in the updated ICO/IARC Report for Serbia, and the cervical cancer mortality rate in Serbia is one of the highest among European countries.

Clinical evaluation of primary human papillomavirus (HPV) testing with extended HPV genotyping triage for cervical cancer screening: A pooled analysis of individual patient data from nine population-based cervical cancer screening studies from China.

To assess the clinical values of extended human papillomavirus (HPV) genotyping in triage of high-risk HPV-positive women, focusing on the trade-off between cervical precancer detections and colposcopy referrals. A bivariate random-effects model was used to estimate the diagnostic accuracy of primary HPV screening with following triage strategies to detect cervical precancers: (i) partial genotyping for HPV16/18 combined with cytological testing at atypical squamous cells of undetermined significance threshold (used as the comparator), (ii) genotyping for HPV16/18/58/52, (iii) genotyping for HPV16/18/58/52/33, (iv) genotyping for HPV16/18/58/33/31, (v) genotyping for HPV16/18/58/52/33/31, and (vi) genotyping for HPV16/18/58/52/33/31/39/51. Internal risk benchmarks for clinical management were used to evaluate the risk stratification of each triage strategy. A total of 16,982 women (mean age 46.1 years, range 17-69) were included in this analysis. For CIN3+ detection, triage with HPV16/18/58/33/31 genotyping achieved lower positivity (6.85% vs. 7.35%, p = 0.001), while maintaining similar sensitivity (91.35% vs. 96.42%, p = 0.32) and specificity (94.09% vs. 93.67%, p = 0.56) compared with the comparator strategy. Similar patterns were observed for CIN2+ detection. Women with a positive HPV16/18/58/33/31 genotyping test had high enough risk for CIN3+ for colposcopy referral, while the risk for women with a negative test was below the 1-year return decision threshold according to internal benchmarks. Our findings suggested extended HPV genotyping is of potential to be used as a triage technique integrated into HPV-based cervical cancer screening, leading to reduced need for colposcopy referral while maintaining similar disease detection and efficient risk stratification.

Allelic loss of HLA class I facilitates evasion from immune surveillance in cervical intraepithelial neoplasia.

Loss of heterozygosity (LOH) has been reported to occur in HLA regions in cervical intraepithelial neoplasia (CIN) and cervical cancer. However, the details of how this is related to the progression of CIN have been unclear. In this study, we examined the human papillomavirus (HPV) antigen-presenting capacity of people with CIN and the significance of LOH of HLA class I in the progression of CIN. It was shown that differences in antigen-presenting capacity among each case depended on HLA types, not HPV genotypes. Focusing on the HLA type, there was a positive correlation between antigen-presenting capacity against HPV and the frequency of allelic loss. Furthermore, the lost HLA-B alleles had a higher HPV antigen-presenting capacity than intact alleles. In addition, frequency of LOH of HLA class I was significantly higher in advanced CIN (CIN2-3) than in cervicitis or early-stage CIN (CIN1): around half of CIN2-3 had LOH of any HLA class I. Moreover, the antigen-presenting capacity against E5, which is the HPV proteins that facilitate viral escape from this immune surveillance by suppressing HLA class I expression, had the most significant impact on the LOH in HLA-B. This study suggests that HPV evades immune surveillance mechanisms when host cells lose the capacity for antigen presentation by HLA class I molecules, resulting in long-term infection and progression to advanced lesions.

Prevalence and Genotype Distribution of HPV in Hangzhou, China.

For women, cervical cancer is the most prevalent cancer and the most common cause of cancer-related deaths worldwide. Human papillomavirus (HPV) is causatively linked to over 90% of cervical cancer cases. Our retrospective study explored the clinical and laboratory data of outpatients with HPV infection to analyze the prevalence and genotype distribution of 3,793 outpatients in the Hangzhou area by using HPV genotype tests. It could provide value for an effective prevention and treatment of HPV infection. In total, 3,793 female outpatients were randomly selected from January 2022 to December 2023. Exfoliated cervical cells were collected using a cytobrush and HPV genotype screening was conducted for testing. Data of all outpatients were collected from the hospital's electronic medical records, and SPSS 26.0 software was used to perform the statistical analysis. Out of 3,793 outpatients, 953 were detected as positive, and the positive rate was 25.13%. The age of the outpatients ranged from 15 - 97, with an average age of 39.91. All outpatients were divided into six age groups. Among the six age groups, the HPV positive rates were, with ascending age, 43.90%, 33.27%, 21.49%, 16.99%, 27.30%, and 25.48%, and the highest positive rate was observed in those aged  20 with a rate of 43.90%. There were significant differences in the positive rates among different age groups (p < 0.05). There were more outpatients with a single infection than with multiple infection (p < 0.05). The positive rate of single infection was the highest in the 31 - 40 and 41 - 50 age groups (74.32% for both) and the positive rate of multiple infection was the highest in the  20 age group (66.67%). Among 24 genotypes, HPV 52, 58, and 51 were the most commonly detected. All three were high-risk genotypes, and HPV 52 was the most dominant in all age groups. As distribution according to quarter, more HPV infection occurred in the fourth quarter, which had a significant difference (p < 0.05). And in the first quarter, the number of HPV positive infections was the lowest. Prevalence and genotype distribution of HPV in the Hangzhou area were different from those of other regions. More single infection, and more multiple infection occurring in low age and in the fourth quarter were the characteristics of HPV infection in the Hangzhou area. It was suggested that vaccine containing HPV 52 might be a better choice for this region.

Multi-cancer early detection (MCED) in circulating tumor DNA (ctDNA) using an ultrasensitive mutation-based amplicon next-generation sequencing (NGS) assay.

e15042 Background: Cancer remains a leading cause of mortality globally. For most cancers, routine screening options are still unavailable. Blood-based MCED has emerged as a promising strategy to bridge this gap. Mutation-based NGS in ctDNA detects highly specific cancer signals, an attribute critical for MCED assays. We developed an ultrasensitive mutation-based NGS assay optimized to detect cancer signals in 50 cancers and predict tissue-of-origin (TOO) for up to 21 cancer classes. Methods: An amplicon-based NGS assay incorporating mirror barcodes for error correction was designed to detect cancer-associated alterations (CAAs), including single nucleotide variants (SNVs), insertion-deletion mutations (indels), and viral DNA (EBV and 20 genotypes of HPV), in 50 cancers. Analytical validation was performed using reference standards and clinical validation was performed in a retrospective case-control cohort of 601 subjects comprising cell-free DNA (cfDNA) from 313 self-declared healthy donors and 288 cancer patients (30.9% early-stage, 50.3% late-stage and 9.4% hematolymphoid cancers). Tissue-of-origin (TOO) was predicted for 21 cancer classes using a weighted sum model. Where relevant, matched buffy coat genomic DNA (gDNA) was analyzed to rule out clonal hematopoiesis. Results: Analytical validation demonstrated a limit of detection (LoD) of 0.05% variant allele frequency (VAF) for indels and 0.07% VAF for SNVs in cfDNA. LoD was matched in gDNA (0.04% and 0.05% VAF for indels and SNVs respectively). In clinical validation, the assay demonstrated a specificity of 99.0% (310/313) and an overall sensitivity of 80.9% (233/288), with sensitivities of 64.0%, 91.7%, and 85.2% in early-stage, late-stage, and hematolymphoid cancers respectively. The mean number of CAAs detected in early-stage, late-stage, and hematolymphoid CAA-positive cancers was 2.1, 3.1, and 4.6. Inclusion of viral targets aided the detection of nasopharyngeal (NPC), cervical, and p16+ oropharyngeal (oPSCC) cancers. EBV DNA was detected in 91.7% of NPC cases. In cervical cancer and p16+ oPSCC, HPV DNA (genotypes 16, 18, 33 and 39) was detected in 71.4% and 90.9% of cases respectively. Conversely, none of the p16- oPSCC cancers had detectable HPV DNA. Across the 21 TOO classes, a high confidence prediction could be made in 62.4% (mean 73.6%, range 26.7%-100%) of cases with an overall accuracy of 87.7% (mean 84.9%, range 33.3%-100%). Overall TOO prediction performance was modeled in a simulated cohort based on cancer incidence in Singapore and Hong Kong, giving an accuracy of 87.3% and 88.7% respectively. Conclusions: The mutation-based NGS assay sensitively detects cancer signals and accurately predicts the tumor origin for early-stage, late-stage, and hematolymphoid cancers. Inclusion of viral targets additionally enables early detection of virus-associated cancers.

Anal human papillomavirus (HPV) disagreement by Linear Array compared to SPF10 PCR-DEIA-LiPA25 system in young sexual minority men

IntroductionYoung sexual minority men (SMM) bear the greatest burden of anal human papillomavirus (HPV) infections. We assessed anal HPV genotype discordance between the Linear Array (LA) and SPF10 PCR-DEIA-LiPA25 (LiPA25). MethodsDiscordance was assessed between LA and LiPA25 using self-collected anal swabs from 120 SMM aged 18–29 who were recruited in 2014–2016. Multiple-type infection was explored as a potential confounder of testing agreement, along with clinical and behavioral factors such as HIV status, syphilis status, incarceration history, health insurance coverage, having 3 or more sex partners in the past 6 months, and co-infection with HPV-16. ResultsSignificant discordance was found for HPV-6, -11, -16, -31, -42, -54, and -59. Exploratory analyses suggest higher prevalence of genotype discordance in those living with HIV, those with 3 or more sex partners, and those who were positive for 4 or more HPV types. ConclusionsOur results highlight the importance of HPV detection methods which may inform different interpretations of research assessing anal HPV natural history among SMM at highest risk for HPV.

EPH231 HPV Genotyping in Invasive Cervical Cancer Samples from Women Attended at an Oncological Hospital between 2017-2021 in Ecuador

EPH231 HPV Genotyping in Invasive Cervical Cancer Samples from Women Attended at an Oncological Hospital between 2017-2021 in Ecuador

Evaluation of an E6/E7 PCR-capillary electrophoresis fragment analysis in the genotyping of human papillomavirus in archival FFPE samples of oropharyngeal cancer.

Accumulating evidence has demonstrated that high-risk human papillomaviruses (HR-HPVs) are involved in the etiology of a subset of oropharyngeal squamous cell carcinoma (OPSCC). In this regard, the International Agency for Research on Cancer (IARC) has recommended direct molecular HPV testing. So far, there is no agreement on the most appropriate method for HPV detection on OPSCC formalin-fixed paraffin-embedded (FFPE) materials. In this study, we aimed to evaluate the performance of the high-sensitive SureX HPV assay in OPSCC FFPE tissues compared with LiPA-25 and p16ink4a immunostaining. A retrospective series of FFPE primary OPSCC cases were diagnosed between 2008 and 2019 and provided by the Henan Cancer Hospital, China. The level of agreement of two assays was determined using Cohen's Kappa (κ) statistics. A total of 230 FFPE OPSCC samples from tumor resections (n = 160) and diagnostic biopsies (n = 70) were detected. Sixty-six (28.7%) and 70 (30.4%) samples were identified as HPV-DNA-positive by LiPA-25 and SureX, respectively, of which HPV16 was largely the most common type (95.5% vs 94.3%). We found a perfect concordance between LiPA-25 and SureX for HPV-DNA status (κ = 0.906, 95% CI: 0.875-0.937) and for HPV16 (κ = 0.925, 95% CI: 0.897-0.953). In addition, SureX and p16ink4a immunostaining had a perfect concordance (κ = 0.917, 95% CI: 0.888-0.946). Moreover, the HPV-driven fraction, based on double positivity for HPV-DNA and p16ink4a, was similar between SureX (63 of 230, 27.4%) and LiPA-25 (60 of 230, 26.1%). Similar results were found in samples from resections and biopsies. SureX and LiPA-25 are comparable. SureX could be used for routine HPV-DNA detection and genotyping on archival OPSCC FFPE tissues.

Dual Epstein-Barr virus and High-Risk Human Papillomavirus infection potentially promotes the occurrence of cervical abnormalities in women living in Southern Morocco

ObjectivesThe aim of this study was to investigate whether Epstein-Barr virus (EBV) acts as a cofactor with Human Papillomavirus (HPV) in the development of cervical abnormalities among women from Southern Morocco. MethodsA total of n = 308 sexually active women were enrolled in this study. EBV and HPV were detected using a nested PCR assay. HPV genotyping was carried out using direct Sanger sequencing assay. Statistical analyses were performed using R/RStudio software. ResultsEBV DNA was detected in 11.04 % of participants. Among these women, 5.84 % were co-infected with HPV and EBV, representing 53 % of women who tested positive for EBV. High-risk HPV genotypes (HR-HPV) were the most common types of dual infections, accounting for 38 % of EBV-positive cases, whereas other genotypes were detected along with EBV in 15 % of cases. Interestingly, a statistically significant association between EBV/HR-HPV and cervical abnormalities was observed in this study (OR 4.58, 95 % CI 1.97–10.60, p = 0.030). In particular, EBV/HR-HPV dual infection was associated with a 7.86-fold increased risk of developing ASCUS-type cervical lesions (OR 7.86, 95 % CI 1.08–37.92, p = 0.017). Moreover, women with several sexual partners were 3.63-folds at a greater risk of contracting an EBV/HR-HPV coinfection (OR 3.63, 95 % CI 0.92–12.32, p = 0.045). ConclusionOur findings suggest that EBV infection alone might not directly promote cervical oncogenesis. However, the possibility of its involvement in coinfection with HR-HPV genotypes remains an area of interest. Further investigations are required to provide firm evidence of the role of EBV in this context.

Human Papillomavirus Infection of the Oropharyngeal and Laryngeal Squamous Papilloma: Disparities in Prevalence and Characteristics.

Human papillomavirus (HPV) infection has emerged as an etiologic factor of squamous papilloma (SP). The oropharynx and larynx are common sites of SP, but studies on the prevalence of HPV infection in these sites are lacking. This study aimed to evaluate and compare the prevalence and characteristics of HPV infection in oropharyngeal SP (OPSP) and laryngeal SP (LSP). HPV detection and genotyping data of patients with pathologically confirmed OPSP and LSP were retrospectively analyzed. A total of 119 patients were enrolled, consisting of 93 patients with OPSP and 26 patients with LSP. Of those patients, 13 patients with OPSP and 14 patients with LSP were positive for HPV infection, accounting for a prevalence of 14.0% and 53.8%, respectively (p < 0.001). The most prevalent genotype was HPV16 in OPSP and HPV6 in LSP. Over two-thirds (69.2%) of HPV(+)-OPSP infections were high-risk types compared with 14.3% of HPV(+)-LSP infections (p = 0.004). The prevalence of HPV infection in patients with OPSP and LSP demonstrated no differences in terms of age, sex, and smoking status. These results could provide a better understanding of HPV infection in OPSP and LSP and serve as a background for the epidemiology of HPV-related tumorigenesis of the oropharynx and larynx.

High-Risk Genotypes of Human Papillomavirus at Diverse Anogenital Sites among Chinese Women: Infection Features and Potential Correlation with Cervical Intraepithelial Neoplasia.

Both cervical cancer and cervical intraepithelial neoplasia (CIN) are associated with human papillomavirus (HPV) infection at different anogenital sites, but the infection features of high-risk (HR) HPVs at these sites and their association with cervical lesions have not been well characterized. Given the limitation of cervical HPV 16/18 test in screening patients with high-grade CIN (CIN 2+), studies on whether non-16/18 HR-HPV subtype(s) have potential as additional indicator(s) to improve CIN 2+ screening are needed. The infection of 15 HR-HPVs in vulva, anus, vagina, and cervix of 499 Chinese women was analyzed, and CIN lesion-associated HR-HPV subtypes were revealed. In addition to the well-known cervical-cancer-associated HPV 16, 52, and 58, HPV 51, 53, and 56 were also identified as high-frequency detected subtypes prevalently and consistently present at the anogenital sites studied, preferentially in multi-infection patterns. HPV 16, 52, 58, 56, and 53 were the top five prevalent subtypes in patients with CIN 2+. In addition, we found that cervical HPV 33/35/52/53/56/58 co-testing with HPV 16/18 might improve CIN 2+ screening performance. This study provided a new insight into HR-HPV screening strategy based on different subtype combinations, which might be used in risk stratification clinically.

Effectiveness of high-risk human papillomavirus genotyping for cervical cancer screening. A multicentre screening cohort study in rural China.

This study aimed to assess the effectiveness of high-risk human papillomavirus (HR-HPV) primary testing for cervical cancer screening in China's rural areas. Women aged 21-64 years were recruited. Cervical cytology was diagnosed following the Bethesda 2001 classification system, HPV infection (HR-HPV, HPV-16, HPV-18, and other 12 genotypes) identified by Cobas-4800, and colposcopy and biopsy performed when required. Primary outcomes were defined as the cumulative incidence of cervical intraepithelial neoplasia grade 2/3/higher (CIN2/3+) and its relative risk at baseline and at the 36-month follow-up. The study included 9,218 women; mean age was 45.15 years (SD: 8.74); 81% completed the follow-up. The most frequent type of cytological lesions (12.4% ) were ASCUS (8.4%) and LSIL (2.2%). HR-HPV infection (16.3%) was more prevalent in HPV-16 than in HPV-18 (3 vs 1.5%); a positive relationship with the severity of the lesions, from 29.8% in ASCUS to 89.6% in HSIL was found. At baseline, 3.5% of the patients underwent colposcopy; 20% had a positive diagnosis. At the 36-month follow-up, the cumulative incidences of CIN2+ and CIN3+ were higher in women with HR-HPV infection (16.9 vs 0.5% and 8.2 vs 0.2%). The relative risk of CIN2/3+ was lower in HR-HPV-negative women compared to those with a negative cytology at baseline (0.4; 95%CI: 0.3-0.4). High-risk HPV-based screening may significantly reduce the risk of CIN2/3+ compared with cytology testing. This may be a new resource for public health demands in China's rural areas.