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Tirbanibulin 1% ointment is a synthetic antiproliferative agent approved in 2021 by the European Union for treating actinic keratoses (AK). Topical tirbanibulin has clinically resolved HPV-57 ( +) squamous cell carcinoma (SCC), HPV-16 ( +) vulvar high-grade squamous intraepithelial lesion, epidermodysplasia verruciformis, and condyloma. We examined how tirbanibulin might affect HPV oncoprotein expression and affect other cellular pathways involved in cell proliferation and transformation. We treated the HeLa cell line, containing integrated HPV-18, with increasing doses of tirbanibulin to determine the effects on cell proliferation. Immunoblotting was performed with antibodies against the Src canonical pathway, HPV 18 E6 and E7 transcription regulation, apoptosis, and invasion and metastasis pathways. Cell proliferation assays with tirbanibulin determined the half-maximal inhibitory concentration (IC 50 ) of HeLa cells to be 31.49 nmol/L. Increasing concentrations of tirbanibulin downregulates the protein expression of Src (p < 0.001), phospho-Src (p < 0.001), Ras (p < 0.01), c-Raf (p < 0.001), ERK1 (p < 0.001), phospho-ERK1 (p < 0.001), phospho-ERK2 (p < 0.01), phospho-Mnk1 (p < 0.001), eIF4E (p < 0.01), phospho-eIF4E (p < 0.001), E6 (p < 0.01), E7 (p < 0.01), Rb (p < 0.01), phospho-Rb (p < 0.001), MDM2 (p < 0.01), E2F1 (p < 0.001), phospho-FAK (p < 0.001), phospho-p130 Cas (p < 0.001), Mcl-1 (p < 0.01), and Bcl-2 (p < 0.001), but upregulates cPARP (p < 0.001), and cPARP/fPARP (p < 0.001). These results demonstrate that tirbanibulin may impact expression of HPV oncoproteins via the Src- MEK- pathway. Tirbanibulin significantly downregulates oncogenic proteins related to cell cycle regulation and cell proliferation while upregulating apoptosis pathways., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Seroepidemiological characteristics of human papillomavirus (HPV) in community residents reflect natural infection and can guide the reform of vaccination programs. A population-based serological survey was conducted in Guangdong Province. Serum anti-HPV IgG antibody levels were determined by an ELISA. Neutralizing antibodies against HPV6, 11, 16, and 18 were detected via a pseudovirus-based neutralization assay (PBNA). A total of 5122 serum samples were collected from community residents, including 1989 males and 3133 females, in three cities of Guangdong Province. The rate of HPV IgG antibody positivity in females was 5.39% (95% CI: 4.6-6.2), which was greater than that in males (2.36%; 95% CI: 1.7-3.1). HPV IgG antibodies were more frequently detected in females aged 51-60 years (11.30%; 95% CI: 7.6-16.0), whereas in males, the detection increased with age and reached 4.94% (95% CI: 2.8-6.9) in the group aged ≥71 years. The seropositivity of neutralizing antibodies against HPV6 and 11 was greater than that against HPV16 and 18. The serum neutralizing antibody titers in individuals who received three doses of a vaccine were 7- to 12-fold greater than those in individuals who did not receive the vaccine. The neutralizing antibody titers slightly decreased within 40 months and ranged from 0.038 to 0.057 log ED50 per month. A moderate consistency between the HPV ELISA and PBNA results was observed (Kappa score = 0.49, r = 0.249, 0.635, 0.382, and 0.466 for HPV6, 11, 16, and 18, respectively). The HPV seropositivity rate among healthy residents of Guangdong Province was found to be low among children and adolescents and to increase with age. The serum neutralizing antibody titers were significantly greater in the vaccine group than that in the control group, and this difference persisted over time, which indicated promising protection against HPV infection., (© 2024 Wiley Periodicals LLC.)

Objectives: The primary objective was to examine the intersurgical interval (ISI) of recurrent respiratory papillomatosis (RRP) in patients older than 45 years before and after a Gardasil vaccination series., Methods: We conducted a retrospective chart review of adult patients >45 years of age diagnosed with RRP from 2012 to 2022. Patients were excluded if they did not receive at least two doses of the Gardasil vaccine series or if they underwent two or fewer surgeries during the study period., Results: Thirteen patients met the inclusion criteria, 11 males and two females. The age at initial diagnosis ranged from 46 to 80 years, with a mean of 59 years. There was a significant increase in the average ISI, from 126 ± 87 days pre-vaccination compared to 494 ± 588 days post-vaccination (p < 0.01). The average number of surgeries per patient was 6.8 ± 2.4 over an average follow-up of 49.7 ± 30.3 months., Conclusion: Adjuvant Gardasil use in RRP patients older than 45 years significantly increases the ISI. Current CDC recommendations include only patients ages 9 to 45, but this study provides evidence that RRP patients outside this age range may benefit from adjuvant HPV vaccination., Level of Evidence: 4 Laryngoscope, 134:3226-3229, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Several observational or retrospective studies have previously been conducted to explore the possible association between lung cancer and human papillomavirus (HPV) infection. However, there may be inconsistencies in the data and conclusions due to differences in study design and HPV testing methods. There are currently no studies that provide conclusive evidence to support the involvement of HPV in the occurrence and development of lung cancer. Therefore, the relationship between HPV and lung cancer remains controversial and uncertain. This study aimed to explore whether HPV infection is causally related to lung cancer risk by systematically performing a two-way Two-Sample Mendelian Randomization (TSMR) analysis., Methods: In the International Lung Cancer Consortium (ILCCO) genome-wide association study dataset, we included 11,348 lung cancer (LUCA) cases, including 3275 squamous cell carcinoma (LUSC) cases, 3442 adenocarcinoma (LUAD) cases, and 15,861 cases of control. Using genetic variants associated with the HPV E7 protein as instrumental variables, we summarized statistics associated with HPV infection in the MRC IEU OpenGWAS database, which included the HPV-16 E7 protein and the HPV-18 E7 protein. Two-sample Mendelian randomization (MR) results are expressed as odds ratios (OR) and 95% confidence intervals (CI)., Results: Based on a comprehensive analysis of genome-wide association study (GWAS) data from public databases, we mainly used inverse-variance weighted (IVW) to estimate causal relationships, while using MR-Egger, weighted median, simple mode, and weighted mode, and other four methods as supplements. Two-sample MR Analysis revealed no causal relationship between exposure factors (HPV-16 E7 protein and HPV-18 E7 protein) and outcome factors (lung cancer (LUCA) and its subtypes squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD)) in forward MR Analysis using the IVW approach.HPV-16 E7 protein and LUCA and its subtypes LUSC and LUAD by IVW method results: [OR] = 1.002; 95% [CI]: 0.961 - 1.045; p = 0.920; [OR] = 1.023; 95% [CI]: 0.966 - 1.084; p = 0.438; [OR] = 0.994; 95% [CI]: 0.927 - 1.066; p = 0.872); HPV-18 E7 protein and LUCA and its subtypes LUSC and LUAD by IVW method results: [OR] = 0.965; 95% [CI]: 0.914 - 1.019; p = 0.197; [OR] = 0.933; 95% [CI]: 0.834 - 1.043; p = 0.222; [OR] = 1.028; 95% [CI]: 0.945 - 1.118; p = 0.524. It was observed through reverse MR that LUCA and its subtypes LUSC and LUAD were used as exposure factors, and HPV infection (HPV-16 E7 protein and HPV-18 E7 protein) was used as the outcome factors, the results of the IVW method are also invalid.LUCA and HPV-16 E7 protein and HPV-18 E7 protein by IVW method results: [OR] = 1.036; 95% [CI]: 0.761 - 1.411; p = 0.82; [OR] = 1.318; 95% [CI]: 0.949 - 1.830; p = 0.099; LUSC and HPV-16 E7 protein and HPV-18 E7 protein by IVW method results: [OR] = 1.123; 95% [CI]0.847 - 1.489; p = 0.421; [OR] = 0.931; 95% [CI]: 0.660 - 1.313; p = 0.682; LUAD and HPV-16 E7 protein and HPV-18 E7 protein by IVW method results: [OR] = 1.182; 95% [CI] 0.983 - 1.421; p = 0.075; [OR] = 1.017; 95% [CI]: 0.817 - 1.267; p = 0.877.Our results indicate that there is no causal relationship between genetically predicted HPV infection and LUCA and its subtypes LUSC and LUAD. In addition, in the reverse MR analysis, we did not observe a significant causal relationship between LUCA and its subtypes LUSC and LUAD on HPV infection., Conclusions: Our findings do not support a genetic association between HPV infection and lung cancer., (© 2024. The Author(s).)

Malignancies of the parotid gland are relatively uncommon and in most cases are primary neoplasms; intraparotid metastases are rare. Oral and oropharyngeal squamous cell carcinoma (O- and OP-SCC) can potentially metastasize to the parotid gland or intraparotid lymph nodes. Fine-needle aspiration cytology (FNAC) serves as the initial diagnostic approach for this purpose. HPV status in FNAC specimens is relevant and can guide the diagnostic workup, indicating a potential oropharyngeal origin of the primary tumor. A small series of occult SCC metastases is presented below, in which HPV-DNA testing of FNAC specimens helped identify primary neoplasms located in the oropharynx. US-guided FNAC of parotid nodules was conducted by an experienced interventional cytopathologist in three cases. Each patient underwent assessment of direct smears, cell blocks, and liquid-based samples for HPV testing. The morphological and immunocytochemical features of SCC were documented, and real-time PCR was employed for the detection and genotyping of HPV. The role of HPV testing on FNAC specimens in pinpointing the primary neoplasms in the oropharynx is highlighted. Consequently, FNAC samples emerge as valuable diagnostic and prognostic tools in this context, providing essential insights for patient management., (© 2024 Wiley Periodicals LLC.)

Juvenile- and adult-onset recurrent respiratory papillomatosis (JORRP and AORRP) are rare but serious conditions that are caused by oral human papillomavirus (HPV) infections. The proliferation of wart-like growths throughout the respiratory tract can result in medical problems, including death. The current treatment scheme is surgery, though prevention of HPV infection through vaccination is available. A previously developed model for JORRP and AORRP was adapted to the United States using data on disease burden and HPV infection. The model was validated against post-vaccination reductions in disease and used to forecast the future burden of JORRP and AORRP, estimating the impact that HPV vaccination will have on these diseases. Between 2007 (the beginning of HPV vaccination in the US) and 2021, this model estimates that approximately 1393 lives, 22,867 Quality-Adjusted-Life-Years, and over USD 672 million in treatment costs have been saved by HPV vaccination. There is also a substantial reduction in JORRP and AORRP burden, with a 95% reduction in incidence by 2040. Moreover, between 2040 and 2121, the model predicts 3-11 total cases of HPV6/11-related JORRP in the US, and 36-267 total cases of HPV6/11-related AORRP. HPV vaccination in the United States has driven, and will continue to drive, substantial reductions in the public health and economic burden of HPV6/11-related JORRP and AORRP.

Human papillomavirus is the most common sexually transmitted infection in the world. Improving knowledge and attitude is the key to controlling and preventing, but women's knowledge about this virus is not enough. This study aimed to determine the effect of educational intervention based on planned behavior theory on knowledge and attitude toward HPV and its vaccination in women of reproductive age. The study was a single-blind, randomized clinical trial study with a control group was done in 2022, which was conducted on 85 women referred to selected comprehensive health centers in Shiraz, Iran. In this study, the sampling was performed is a multi-stage random way. Eighty-three women who met the inclusion criteria were randomly divided into two intervention and control groups. The data collection tool was the knowledge and attitude questionnaire about HPV and its vaccine, which was confirmed to be valid and reliable. Data analysis was performed with descriptive and analytic statistics at a significance level of P < 0.05 with SPSS (22) software. The results showed that the educational intervention has caused a significant increase in the components of knowledge, attitude, social norms, perceived behavior control, and willingness to receive the HPV vaccine in the intervention group. So that in both stages after the intervention, there was a significant difference between the intervention group and the control group in the studied components (P < 0.05). The educational intervention based on the planned behavior theory significantly affected the knowledge, attitude, social norms, and intention for HPV vaccination in women of reproductive age. Therefore, educational intervention recommended as awareness-raising programs and strategies for women.Trial registration: (RCT code: IRCT20220131053891N1). First Registration date: 28/04/2022., (© 2024. The Author(s).)

Validation of bioanalytical methods is crucial, especially in the pharmaceutical industry, to determine their suitability for specific purposes and the accuracy of analytical results. The pseudovirion-based neutralization assay (PBNA) is considered the gold standard for detecting and quantifying neutralizing antibodies against human papillomavirus in vaccine development for disease prevention. This paper introduces an improved triple-color PBNA method, capable of simultaneous detection of two or three human papillomavirus (HPV types for use in the development of a 14-valent HPV vaccine candidate. The primary objective was to comprehensively validate the triple-color PBNA method for general vaccine immunogenicity assays. Results show that the method has good specificity, accuracy, precision, linearity, robustness, and applicability. This innovative triple-color PBNA offers an improved approach for large-scale immunogenicity assessment in vaccine development. This study lays a solid foundation that can serve as a guiding paradigm for assessing vaccine responses in preclinical and clinical phases, providing valuable insights to the field., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Human papillomavirus (HPV) proteins may elicit antibody responses in the process toward HPV-related malignancy. However, HPV seroepidemiology in noncervical HPV-related cancers remains poorly understood, particularly in populations with a high prevalence of human immunodeficiency virus (HIV). Using a glutathione S-transferase-based multiplex serology assay, antibodies against E6, E7 and L1 proteins of HPV16 and HPV18 were measured in sera of 535 cases of noncervical HPV-related cancers (anal (n = 104), vulval (n = 211), vaginal (n = 49), penile (n = 37) and oropharyngeal (n = 134)) and 6651 non-infection-related cancer controls, from the Johannesburg Cancer Study that recruited Black South African with newly diagnosed cancer between 1995 and 2016. Logistic and Poisson regression models were used to calculate adjusted odds ratios (aOR) and prevalence ratios (aPR) and 95% confidence intervals (CI) in cases versus controls. HPV16 E6 was more strongly associated with noncervical HPV-related cancers than HPV16 L1 or E7, or HPV18 proteins: anal (females (HPV16 E6 aOR = 11.50;95%CI:6.0-22.2), males (aOR = 10.12;95%CI:4.9-20.8), vulval (aOR = 11.69;95%CI:7.9-17.2), vaginal (aOR = 10.26;95%CI:5.0-21), penile (aOR = 18.95;95%CI:8.9-40), and oropharyngeal (females (aOR = 8.95;95%CI:2.9-27.5), males (aOR = 3.49;95%CI:1.8-7.0)) cancers. HPV16-E6 seropositivity ranged from 24.0% to 35.1% in anal, vulval, vaginal and penile cancer but was significantly lower (11.2%) in oropharyngeal cancer. After adjustment for HIV, prevalence of which increased from 22.2% in 1995-2005 to 54.1% in 2010-2016, HPV16 E6 seropositivity increased by period of diagnosis (aPR for 2010-2016 vs. 1995-2006 = 1.84;95%CI:1.1-3.0). Assuming HPV16 E6 seroprevalence reflects HPV attributable fraction, the proportion of certain noncervical-HPV-related cancers caused by HPV is increasing over time in South Africa. This is expected to be driven by the increasing influence of HIV., (© 2024 International Agency for Research on Cancer. International Agency for Research on Cancer retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Background: High-risk human papillomavirus (HR-HPV) infection is an important factor for the development of cervical cancer. HPV18 is the second most common HR-HPV after HPV16., Methods: In this study, MEGA11 software was used to analyze the variation and phylogenetic tree of HPV18 E6-E7 and L1 genes. The selective pressure to E6, E7 and L1 genes was estimated using pamlX. In addition, the B cell epitopes of L1 amino acid sequences and T cell epitopes of E6-E7 amino acid sequences in HPV18 were predicted by ABCpred server and IEDB website, respectively., Results: A total of 9 single nucleotide variants were found in E6-E7 sequences, of which 2 were nonsynonymous variants and 7 were synonymous variants. Twenty single nucleotide variants were identified in L1 sequence, including 11 nonsynonymous variants and 9 synonymous variants. Phylogenetic analysis showed that E6-E7 and L1 sequences were all distributed in A lineage. In HPV18 E6, E7 and L1 sequences, no positively selected site was found. The nonconservative substitution R545C in L1 affected hypothetical B cell epitope. Two nonconservative substitutions, S82A in E6, and R53Q in E7, impacted multiple hypothetical T cell epitopes., Conclusion: The sequence variation data of HPV18 may lay a foundation for the virus diagnosis, further study of cervical cancer and vaccine design in central China., (© 2024. The Author(s).)

Objectives: This study aimed to assess current vaccination rates among health care workers at risk for occupational human papillomavirus (HPV) exposure and explore factors that influence decisions about HPV vaccination., Design: Using a mixed-methods design, this study included a questionnaire and qualitative focus groups., Setting: The study took place at an academic medical center., Participants: Participants were 37 health care professionals in occupations at risk for workplace HPV exposure., Main Outcome Measures: The primary qualitative outcome measured was HPV vaccination status. The primary qualitative outcomes assessed were perceptions of occupational HPV exposure risk, protective measures, and HPV vaccination., Results: Most participants were female (86.5%, n = 32) and younger than 35 years (51.4%; n = 19) and therefore would have been eligible to receive the HPV vaccine series as a teenager or young adult. Nearly two-thirds (67.6%; n = 25) of participants had received the HPV vaccine; of those, half were vaccinated as teenagers (52%; n = 13). One-third (n = 4) of those vaccinated as adults reported vaccination due to workplace HPV exposure. Focus groups revealed themes consistent with the Health Belief Model. Most participants recognized their risk of aerosolized HPV exposure in the workplace but felt uneducated about occupational exposure risk and protective measures. Many participants recognized risk of exposure through surgical smoke but perceived that risk was stratified by medical specialty, proximity to surgical field, and personal protective equipment use. Many participants had some level of concern for head and neck lesions with exposure to aerosolized HPV. Most participants recognized the need to protect themselves against workplace HPV exposure. Those who were vaccinated felt that they were better protected against HPV exposure. Almost all participants said that they had not received formal education on workplace HPV exposure risk. Many participants voiced perceived barriers to HPV vaccination., Conclusion: Health care workers encounter the HPV virus in a myriad of fields and procedures. Our mixed-methods study demonstrated that at-risk health care workers feel uninformed about their risk of HPV exposure in the workplace, availability of HPV vaccination, and appropriate protective equipment recommendations., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Several types of human papillomavirus (HPV) vaccines have been approved for use in adolescent girls in China. These vaccines are regulated as non-National Immunisation Program vaccines and are optional and generally fully self-paid by vaccinees., Objective: To assess parents' demand for HPV vaccination by eliciting their willingness-to-pay for their adolescent daughters to be vaccinated against HPV and to examine the determinants of demand for HPV vaccination in China., Methods: A contingent valuation survey was conducted across three cities in Shandong Province in eastern China. We selected 11 junior middle schools with different socioeconomic features and randomly selected 6 classes in each school, and questionnaires were distributed to all girls aged 12-16 in the 66 classes for their parents to complete. A payment card approach was used to elicit parental willingness-to-pay for HPV vaccination for their daughters. We also collected a wide array of socioeconomic and psychological variables and interval regressions were applied to examine the determinants of parental willingness-to-pay., Results: A total of 1074 eligible parents who completed valid questions were included in analyses. Over 85% of parents believed HPV vaccines were, in general, necessary and beneficiary. However, only around 10% believed that their daughters would be infected by HPV. About 8% of parents would not accept HPV vaccine even if the vaccine were free mainly due to concerns about the potential side effects and vaccine safety and quality issues, and 27.37% would only accept the vaccine if it were free. The median willingness-to-pay was 300 CNY (42 USD). Several factors were positively correlated with higher willingness-to-pay: income, urban residence (relative to rural residence), mothers (relative to fathers), parents' beliefs about vaccine benefits, whether they should make decisions for their daughters, and whether their daughters would be susceptible to HPV. Though education-level was not significantly correlated with willingness-to-pay in the main regressions, a subgroup analysis revealed interesting dynamics in the relation between education and willingness-to-pay across different income-levels., Conclusions: There is a large gap between parents' willingness-to-pay and the market price of HPV vaccine for girls in China. Parents generally believed the HPV vaccines were beneficial and necessary but when asked for their daughters, most parents did not believe their daughters would be infected by HPV despite the high prevalence in China. Future focus should be on ensuring the provision of accurate health information about HPV prevalence, vaccine quality, and safety to promote vaccine uptake, and promotional efforts tailored to different income groups might yield better effects. Government involvement in negotiating more widely acceptable and affordable prices or subsidising may be necessary for protecting high-risk population groups., (© 2024 John Wiley & Sons Ltd.)

Cervical cancer is the fourth most common malignancy in women worldwide. The identification of human papillomavirus (HPV) as the main etiologic cause of cervical cancer has led to the development and adaptation of HPV molecular diagnostics as a cervical cancer screening and prevention tool. This article highlights six Food and Drug Administration-approved HPV molecular platforms, each with unique advantages and disadvantages. In addition, HPV vaccination and the emergence of HPV self-collection as an alternative testing strategy are discussed., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

High-risk human papillomavirus (HPV) infections can progress to cervical cancer which is the fourth most common cancer in women globally. In Scotland, the incidence of cervical cancer has a strong socioeconomic deprivation gradient disproportionately affecting women from more deprived areas. An HPV vaccination programme was initiated in Scotland in 2008 targeting girls aged 12-13 years with a catch-up campaign running for the first three years for girls aged up to 18 years. The programme has evolved over the last 16 years with changes in the type of vaccine, dosing schedules and the extension of the programme to boys and gay, bisexual and other men who have sex with men. Vaccine uptake in Scotland has historically been high but has gradually decreased over time and disparities exist in women from more deprived areas of Scotland. The ability to link national immunisation and screening databases in Scotland has allowed direct monitoring of the impact of the HPV vaccine on virological and histological outcomes. Analyses of this linked data have demonstrated real-world evidence of high vaccine effectiveness against HPV infection, cervical disease, and cervical cancer with evidence of herd immunity in unvaccinated women. Continued monitoring is crucial to assess the duration of protection, the impact of vaccine and dosing schedules changes and the emergence of potential type replacement. With the World Health Organisation's aim to eliminate cervical cancer as a public health problem by the next century addressing the inequalities in cervical cancer incidence will be crucial. This will require targeted interventions for women most at risk of cervical cancer to ensure elimination is achieved timely for all women in Scotland., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kate Cuschieri reports a relationship with Hologic Inc. that includes: funding grants and travel reimbursement. Kate Cuschieri reports a relationship with Barinthus Biotherapeutics plc that includes: funding grants and non-financial support. Kate Cuschieri reports a relationship with EUROIMMUN Medizinische Labordiagnostika AG that includes: funding grants. Kate Cuschieri reports a relationship with GeneFirst that includes: funding grants. Kate Cuschieri reports a relationship with Hiantis that includes: funding grants. Kate Cuschieri reports a relationship with Seegene, Inc. that includes: funding grants. Kate Cuschieri reports a relationship with Roche that includes: funding grants. Kate Cuschieri reports a relationship with Daye that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Human Papillomavirus (HPV), an extensive family of DNA viruses, manifests as a persistent global health challenge. Persistent HPV infection is now firmly established as a significant aetiological factor for a spectrum of malignancies. In this review, we examine the latest insights into HPV biology and its intricate relationship with the host. We delve into the complex dynamics of co-infections involving HPV alongside other viruses, such as HIV, EBV, and HSV, as well as the burgeoning role of the microbiome in cancer development. We also explore recent advancements in understanding the specific contributions of HPV in the development of various cancers, encompassing cancers of the anogenital region, head and neck, as well as breast, lung, and prostate. Moreover, we focus on the current preventive strategies, including vaccination and screening methods, and therapeutic interventions that range from traditional approaches like surgery and chemotherapy to emerging modalities such as targeted therapies and immunotherapies. Additionally, we provide a forward-looking view on the future directions of HPV research, highlighting potential areas of exploration to further our understanding and management of HPV and its associated cancers. Collectively, this review is positioned to deepen readers' understanding of HPV biology and its complex interplay with cancer biology. It presents innovative strategies for the prevention, management, and therapeutic intervention of HPV-associated malignancies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Huang, Tang, Ren, Jiang, Tian and Li.)

Human papillomavirus (HPV) is an important causative factor of cervical cancer and is associated with nonsmall cell lung cancer (NSCLC). Merkel cell polyomavirus (MCPyV) is a rare and highly fatal cutaneous virus that can cause Merkel cell carcinoma (MCC). Although coinfection with oncogenic HPV and MCPyV may increase cancer risk, a definitive etiological link has not been established. Recently, genomic variation and genetic diversity in the MCPyV noncoding control region (NCCR) among ethnic groups has been reported. The current study aimed to provide accurate prevalence information on HPV and MCPyV infection/coinfection in NSCLC patients and to evaluate and confirm Korean MCPyV NCCR variant genotypes and sequences. DNA from 150 NSCLC tissues and 150 adjacent control tissues was assessed via polymerase chain reaction (PCR) targeting regions of the large T antigen (LT-ag), viral capsid protein 1 (VP1), and NCCR. MCPyV was detected in 22.7% (34 of 150) of NSCLC tissues and 8.0% (12 of 150) of adjacent tissues from Korean patients. The incidence rates of HPV with and without MCPyV were 26.5% (nine of 34) and 12.9% (15 of 116). The MCPyV NCCR genotype prevalence in Korean patients was 21.3% (32 of 150) for subtype I and 6% (nine of 150) for subtype IIc. Subtype I, a predominant East Asian strain containing 25 bp tandem repeats, was most common in the MCPyV NCCR data set. Our results confirm that coinfection with other tumor-associated viruses is not associated with NSCLC. Although the role of NCCR rearrangements in MCPyV infection remains unknown, future studies are warranted to determine the associations of MCPyV NCCR sequence rearrangements with specific diseases., (© 2024 Wiley Periodicals LLC.)

The role of Human papillomavirus (HPV) infection in esophageal squamous cell carcinoma (ESCC) is a topic of ongoing debate. This study used two screening approaches to look for evidence of HPV infection in esophageal squamous cell carcinoma. We initially checked for HPV infection in a randomly selected group of 53 ESCC cases. We did not detect any tumors positive for high-risk HPV. However, during clinical practice, we identified an HPV-positive ESCC in the distal esophagus, which tested positive for HPV16. This index case was TP53 wild-type, as determined by next-generation DNA sequencing (NGS). Since TP53 mutations are rare in other HPV-driven cancers, we improved our screening method by limiting our screen to a subset of ESCC cases without TP53 mutations. A second screen of 95 ESCCs (from 93 patients) sequenced by NGS revealed an additional 7 ESCCs with TP53 wild-type status (7.3% of the total). Of the 7 cases, 2 cases were found to be high-risk HPV positive. Both patients also tested positive for circulating cell-free HPV DNA and had a complete response to neoadjuvant chemoradiation. The index patient had microscopic residual tumor following neoadjuvant therapy. The patient underwent adjuvant immunotherapy and remained disease free after 22 months of surveillance. This study affirms the transcriptionally active status of high-risk HPV in a minority of ESCC patients in North America., Competing Interests: Conflicts of Interest and Source of Funding: J.M.C. receives research funding for his institution from Merus, Roche, Servier, and Bristol Myers Squibb. He receives research support from Merck, AstraZeneca, Esperas Pharma, Bayer, Tesaro, Arcus Biosciences, and Apexigen; he additionally received honoraria for serving on the advisory board of Incyte and Blueprint Medicines. K.P. serves as one-time advisory board member of Ipsen, Exelesis, Lantheus, and Novartis. BMH received honoraria for serving on the advisory board of Loxo@Lilly. R.D.O. serves as president for Dr Robert Odze Pathology LLC Odzepathology.com. For the remaining authors none were declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The French cancer control strategy 2021-2030 aims to achieve 80 % human papillomavirus (HPV) vaccination coverage. Since 2021, HPV vaccination is also recommended for boys aged 11-14 years, with a catch-up vaccination recommended for unvaccinated adolescents aged ≤19 years. The PAPILLON study used claims data to monitor the evolution of HPV Vaccination Coverage Rate (VCR) in the French population., Methods: The annual HPV VCR was described from 2017 to 2022. Partial vaccination was defined as the dispensing of at least one dose of HPV vaccination. Full scheme vaccination was defined according to the current French recommendations as two or three doses of HPV vaccine over an 18-month period. Annual HPV vaccine initiation rates were estimated on 11-14 and 15-19-year-olds adolescents. Cumulative VCR were estimated on adolescents aged between 11 and 19 years at the time of first vaccination., Results: Overall, 1,773,900 females and 592,167 males initiated HPV vaccination between 2017 and 2022. Initiations occurred between 11 and 14 years for 67.3 % of females and 62.4 % of males with a median time between the first two doses of 195 days and 190 days, respectively. In girls, the cumulative vaccination rate for the partial scheme vaccination at 15 y.o. increased from 28.1 % in 2017 to 50.9 % in 2022. Similarly, the cumulative vaccination rate for the full scheme vaccination at 16 y.o. increased from 15.5 % in 2017 to 33.8 % in 2022. In 2022, the initiation rates for males were 12.6 % at age 14 and 1.9 % at age 19., Conclusions: HPV vaccination coverage increased between 2017 and 2022 among girls targeted by the recommendation but remains insufficient. The results of this study show a tentative but promising start to vaccination in boys. This study will monitor the effects of actions taken to improve vaccination, including the extension of vaccination competencies to community pharmacists since end of 2022., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gerard de Pouvourville reports financial support was provided by MSD France. Jean-Jacques Baldauf reports financial support was provided by MSD France. M. Belhassen, M. Bérard, E. Guyot and F. Jacoud are full-time employees of PELyon. L. Bensimon and G. Farge are full-time employees of MSD France., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We have demonstrated that SAMHD1 (sterile alpha motif and histidine-aspartic domain HD-containing protein 1) is a restriction factor for the human papillomavirus 16 (HPV16) life cycle. Here, we demonstrate that in HPV-negative cervical cancer C33a cells and human foreskin keratinocytes immortalized by HPV16 (HFK+HPV16), SAMHD1 is recruited to E1-E2 replicating DNA. Homologous recombination (HR) factors are required for HPV16 replication, and viral replication promotes phosphorylation of SAMHD1, which converts it from a dNTPase to an HR factor independent from E6/E7 expression. A SAMHD1 phospho-mimic (SAMHD1 T592D) reduces E1-E2-mediated DNA replication in C33a cells and has enhanced recruitment to the replicating DNA. In HFK+HPV16 cells, SAMHD1 T592D is recruited to the viral DNA and attenuates cellular growth, but does not attenuate growth in isogenic HFK cells immortalized by E6/E7 alone. SAMHD1 T592D also attenuates the development of viral replication foci following keratinocyte differentiation. The results indicated that enhanced SAMHD1 phosphorylation could be therapeutically beneficial in cells with HPV16 replicating genomes. Protein phosphatase 2A (PP2A) can dephosphorylate SAMHD1, and PP2A function can be inhibited by endothall. We demonstrate that endothall reduces E1-E2 replication and promotes SAMHD1 recruitment to E1-E2 replicating DNA, mimicking the SAMHD1 T592D phenotypes. Finally, we demonstrate that in head and neck cancer cell lines with HPV16 episomal genomes, endothall attenuates their growth and promotes recruitment of SAMHD1 to the viral genome. The results suggest that targeting cellular phosphatases has therapeutic potential for the treatment of HPV infections and cancers., Importance: Human papillomaviruses (HPVs) are causative agents in around 5% of all human cancers. The development of anti-viral therapeutics depends upon an increased understanding of the viral life cycle. Here, we demonstrate that HPV16 replication converts sterile alpha motif and histidine-aspartic domain HD-containing protein 1 (SAMHD1) into a homologous recombination (HR) factor via phosphorylation. This phosphorylation promotes recruitment of SAMHD1 to viral DNA to assist with replication. A SAMHD1 mutant that mimics phosphorylation is hyper-recruited to viral DNA and attenuates viral replication. Expression of this mutant in HPV16-immortalized cells attenuates the growth of these cells, but not cells immortalized by the viral oncogenes E6/E7 alone. Finally, we demonstrate that the phosphatase inhibitor endothall promotes hyper-recruitment of endogenous SAMHD1 to HPV16 replicating DNA and can attenuate the growth of both HPV16-immortalized human foreskin keratinocytes (HFKs) and HPV16-positive head and neck cancer cell lines. We propose that phosphatase inhibitors represent a novel tool for combating HPV infections and disease., Competing Interests: The authors declare no conflict of interest.

Importance: To inform the design and implementation of targeted interventions to reduce the future burden of human papillomavirus (HPV)-related cancers in Texas, it is necessary to examine the county and health service region (HSR) levels of (1) the proportion of children and teenagers aged 9 to 17 years who initiated and were up to date for HPV vaccination series and (2) HPV-related cancer incidence rates (IRs)., Objective: To evaluate temporal trends and geospatial patterns of HPV vaccination initiation and up-to-date status as well as HPV-related cancer rates at county and HSR levels in Texas., Design, Setting, and Participants: This population-based cross-sectional study used data from the Texas Immunization Registry, the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database, and Texas Department of State Health Services annual population counts from 2006 to 2022. The analysis of HPV vaccination rates was conducted among children and teenagers aged 9 to 17 years; the analysis of HPV-related cancer rates was conducted among adults aged 20 years and older. Data were extracted between June and July 2023 and statistical analysis was performed from February to April 2024., Main Outcomes and Measures: HPV vaccination initiation and up-to-date status rates and HPV-related cancer IR at county and HSR levels., Results: A total of 32 270 243 children and teenagers (65.8% female individuals and 34.2% male individuals) and 22 490 105 individuals aged 20 years and older (50.7% female individuals and 49.3% male individuals) were included. The mean 2021 to 2022 county-level HPV vaccination series initiation estimates ranged from 6.3% to 69.1% for female and from 7.0% to 77.6% for male children and teenagers aged 9 to 17 years. County-level vaccination up-to-date estimates were generally lower compared with those of initiation estimates and ranged from 1.6% to 30.4% for female and from 2.1% to 34.8% for male children and teenagers. The pattern of HPV vaccination rates stratified by sex were similar across counties and HSRs. The age-adjusted annual HPV-related cancer IR by county for years 2016 to 2020 ranged from 0 to 154.2 per 100 000 for female individuals and from 0 to 60.1 per 100 000 for male individuals. The counties located in North Texas, HSRs 2/3 and 4/5N, had lower HPV vaccination rates and higher IRs of HPV-related cancers for both female and male individuals compared with other regions., Conclusions and Relevance: In this study, the incidence of HPV-related cancers varied widely across the counties and HSRs of Texas. More counties in North Texas, HSRs 2/3 and 4/5N, had higher IRs of HPV-related cancers and a lower proportion of HPV vaccination rates than counties in other regions. Designing and implementing targeted interventions to increase uptake and completion of HPV vaccination series across counties with low HPV vaccination rates may help to reduce future the burden of HPV-related cancers.

This study aimed to report the clinical outcomes and risk factors for survival of patients with low-risk early-stage human papillomavirus-associated (HPVA) endocervical adenocarcinoma (EAC) treated with surgery alone. This retrospective study obtained the clinicopathological data of patients with early-stage HPVA EAC who underwent surgery between 2012 and 2018. The Silva pattern of invasion was determined by reviewing pathology slides. Locoregional recurrence-free survival (RFS), RFS, and overall survival were calculated, and the risk factors for survival were analyzed. One hundred seventeen patients with a median follow-up of 5.2 years (0.5-9.7 yr) were included. The most common histologic type was usual (94/117, 80.3%). The Silva pattern was A in 79 patients (67.5%), B in 30 (25.6%), and C in 8 (6.8%). The 5-year locoregional RFS, RFS, and overall survival rates were 92.4%, 87.8%, and 97.2%, respectively. The presence of intermediate-risk factors and Silva pattern C were significantly associated with worse survival. Based on these findings, patients were categorized into 2 groups: Group 1 (Silva pattern A or Silva pattern B without intermediate-risk factors) and Group 2 (Silva pattern B with intermediate-risk factors or Silva pattern C ). Group 2 showed significantly worse outcomes than Group 1, including the 5-year locoregional RFS (98.6% vs 68.0%), RFS (96.4% vs 54.6%), and overall survival (100.0% vs 86.5%). In conclusion, surgery alone for early-stage HPVA EAC resulted in favorable outcomes. Consideration of the Silva pattern, in addition to well-known risk factors, could help in precise risk group stratification of low-risk, early-stage HPVA EAC., Competing Interests: H.S.K.’s work is supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIT; 2023R1A2C2006223). The remaining authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Japan is lagging in cervical cancer prevention. The effectiveness of a self-sampling human papillomavirus (HPV) test, a possible measure to overcome this situation, has not yet been evaluated. A randomized controlled trial was performed to evaluate the effectiveness of a self-sampling HPV test on detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and screening uptake. Women between 30 and 58 years old who did not participate in the cervical cancer screening program for ≥3 years were eligible and assigned to the intervention group (cytology or self-sampling HPV test) or control group (cytology). Participants assigned to the intervention group were sent a self-sampling kit according to their ordering (opt-in strategy). A total of 7337 and 7772 women were assigned to the intervention and control groups, respectively. Screening uptake in the intervention group was significantly higher than that in the control group (20.0% vs. 6.4%; risk ratio: 3.10; 95% confidence interval [CI]: 2.82, 3.42). The compliance rate with cytology triage for HPV-positive women was 46.8% (95% CI: 35.5%, 58.4%). CIN2+ was detected in five and four participants in the intervention and control groups, respectively; there was no difference for intention-to-screen analysis (risk ratio: 1.32; 95% CI: 0.36, 4.93). Self-sampling of HPV test increased screening uptake; however, no difference was observed in the detection of CIN2+, probably due to the low compliance rate for cytology triage in HPV-positive women. Efforts to increase cytology triage are essential to maximize precancer detections., (© 2024 UICC.)

Objective: We conducted a systematic review to assess the scope and effectiveness of interventions to improve human papilloma virus (HPV) vaccination in Africa from 2006 to 2021., Study Design: Systematic review., Methods: Four databases (Medline, Embase, CINAHL and PsycINFO) were searched for articles published between 2006 and 2021. Articles were screened and included based on eligibility criteria using DistillerSR (Version 2.35). Data were extracted and reported using a narrative synthesis. A quality assessment was also conducted for each study using validated quality appraisal tools., Results: Out of 7603 articles identified by a systematic search, 18 articles met the inclusion criteria. Included studies comprised impact evaluation and cross-sectional studies published between 2012 and 2021 and conducted in eight African countries namely: Nigeria, Cameroon, South Africa, Kenya, Tanzania, Zambia, Mali, and Malawi. Study quality ranged from high to low quality. Interventions comprised fifteen educational and three multicomponent interventions. Out of thirteen impact evaluation studies (all educational interventions), twelve studies were effective in increasing HPV vaccine uptake and/or improving participants' knowledge, attitudes, and perceptions about the vaccine. Across five cross-sectional studies (two educational and three multicomponent interventions), HPV vaccine uptake rates ranged from 34% to 93.3%, with a consensus on safety and effectiveness in 67.9%-90.3% of participants post-intervention., Conclusion: Educational and multicomponent interventions have been implemented to improve HPV vaccination in Africa. While educational interventions have proven effective at improving HPV vaccine uptake, a more diverse range of interventions with robust impact evaluation study designs are needed to strengthen the available evidence and improve vaccine uptake., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: To investigate the causal relationship between human papillomavirus (HPV) and lung cancer, we conducted a study using the two-sample Mendelian randomization (TSMR)., Method: Data from genome-wide association studies (GWAS) were analyzed with HPV E7 Type 16 and HPV E7 Type 18 as exposure factors. The outcome variables included lung cancer, small cell lung cancer, adenocarcinoma and squamous cell lung cancer. Causality was estimated using inverse variance weighted (IVW), MR-Egger and weighted median methods. Heterogeneity testing, sensitivity analysis, and multiple validity analysis were also performed.., Results: The results showed that HPV E7 Type 16 infection was associated with a higher risk of squamous cell lung cancer (OR = 7.69; 95% CI:1.98-29.85; p = 0.0149). HPV E7 Type 18 infection significantly increased the risk of lung adenocarcinoma (OR = 0.71; 95% CI: 0.38-1.31; p = 0.0079) and lung cancer (OR = 7.69; 95% CI:1.98-29.85; p = 0.0292). No significant causal relationship was found between HPV E7 Type 16 and lung adenocarcinoma, lung cancer, or small cell lung carcinoma, and between HPV E7 Type 18 and squamous cell lung cancer or small cell lung carcinoma., Conclusions: This study has revealed a causal relationship between HPV and lung cancers. Our findings provide valuable insights for further mechanistic and clinical studies on HPV-mediated cancer., Competing Interests: Declaration of competing interest All the authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Nitric oxide (NO) may contribute to the persistence of high-risk human papillomavirus (hrHPV) infection, which has been linked to the development of premalignant lesions and cervical cancer. Our study aimed to examine the relationship between cervical NO metabolite (NOx) levels, hrHPV infection, and cytopathological findings. Additionally, we assessed cervical NOx levels as a biomarker for predicting hrHPV infection and epithelial atypia., Methods: The study involved 74 women who attended the Gynecology and Obstetrics outpatient clinics at Cairo University Hospitals between November 2021 and August 2022. Cervical samples were subjected to Pap testing, assessment of NOx levels by the Griess method, and detection of hrHPV DNA by real-time polymerase chain reaction., Results: High-risk HPV was detected in 37.8% of women. EA was found in 17.1% of cases, with a higher percentage among hrHPV-positive than negative cases (35.7% vs. 4.3%, p = 0.001). The most prevalent hrHPV genotype was HPV 16 (89.3%). The cervical NOx level in hrHPV-positive cases was significantly higher (37.4 µmol/mL, IQR: 34.5-45.8) compared to negative cases (2.3 µmol/mL, IQR: 1.2-9.8) (p = < 0.001). Patients with high-grade atypia showed significantly higher NOx levels (38.0 µmol/mL, IQR: 24.6-94.7) in comparison to NILM and low-grade atypia cases (5.0 µmol/mL, IQR: 1.6-33.3 and 34.5 µmol/mL, IQR: 11.7-61.7, respectively) (p = 0.006). Although the NOx levels among hrHPV-positive cases with low-grade atypia (40.4 µmol/mL, IQR: 33.3‒61.8) were higher than those with NILM (36.2 µmol/mL, IQR: 35.7‒44.0) and high-grade atypia (38.0 µmol/mL, IQR: 24.6‒94.7), the difference was not significant (p = 0.771). ROC curve analysis indicated that the cervical NOx cut-off values of > 23.61 µmol/mL and > 11.35 µmol/mL exhibited good diagnostic accuracy for the prediction of hrHPV infection and EA, respectively., Conclusions: The high prevalence of hrHPV infection, particularly HPV 16, in our hospital warrants targeted treatment and comprehensive screening. Elevated cervical NOx levels are associated with hrHPV infection and high-grade atypia, suggesting their potential use as biomarkers for predicting the presence of hrHPV and abnormal cytological changes., (© 2024. The Author(s).)

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., (© 2024 The Author(s). Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Human papillomavirus (HPV) is an oncogenic DNA virus that plays a role in different cancer types. The aim of this study was to detect the prevalence and types of HPV and its relation with p16, EGFR and clinical findings in lung cancer. HPV and EGFR detection and genotyping of HPV were performed by polymerase chain reaction (PCR) and p16 by immunohistochemistry. Fifty lung cancer patients and seven patients with non-neoplastic lung disease were enrolled in this study. HPV was positive in 78% (39/50) of lung cancer cases. HPV 51 was the most frequent type, followed by HPV 16. Moreover, p16 was positive in 24% (12/50) of the cancer patients, and all of these patients were HPV-positive, while 27 HPV-positive patients showed no p16 expression. There was no relationship between HPV infection and p16 ( p = 0.05), gender ( p = 0.42), age ( p = 0.38), or smoking history ( p = 0.68). Although not statistically significant, the HPV prevalence was found to be higher in cancer patients compared to non-neoplastic patients. The prevalence of HPV in lung cancer varies across different studies, which may be due to differences in the detection methods, number of patients, geographic regions, and vaccination status. Further studies are necessary to understand the role of HPV in lung cancer pathogenesis.

Background: The study aimed to evaluate the positivity rates and genotype distribution of the multiplex PCR capillary electrophoresis (MPCE) and PCR-Reverse Dot Blot (PCR-RDB) assays for human papillomavirus (HPV) detection in cervical cancer tissue specimens, and to explore their detection principles and applications in large-scale population screening., Methods: The MPCE and PCR-RDB assays were performed separately on 425 diagnosed cervical cancer tissue specimens. Subsequently, the results of both assays were compared based on the HPV infection positivity rates and genotype distribution., Results: The overall positive rates of HPV genotypes for the MPCE and PCR-RDB assays were 97.9% and 92.9%, respectively. A p -value < 0.001 indicated a statistically significance difference in consistency between the two assays. The kappa value was 0.390, indicating that the consistency between both assays was fair. HPV16 was the most common single-genotype infection type, with infection rates detected via MPCE and PCR-RDB assays being 75.7% and 68.3%, respectively. In the age group >50 years, the HPV multiple-type infection rate detected via MPCE assay was significantly higher than that detected by the PCR-RDB assay, with a statistically significant difference ( p = 0.002)., Conclusion: To reduce the false-negative rate and improve screening efficiency, the MPCE assay, which targets the oncogenic gene E6/E7 segments, can be extended to the general female population for the early detection, diagnosis, and treatment of cervical cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qin, Li, Wang, Lan, Han, Mei and Geng.)

The incidence rate of human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is increasing in countries with high human development index. HPV cell-free DNA (cfDNA) isolated from 3 to 4 mL blood plasma has been successfully used for therapy surveillance. A highly discussed application of HPV-cfDNA is early detection of HPV-OPC. This requires sensitive and specific cfDNA detection as cfDNA levels can be very low. To study the predictive power of pre-diagnostic HPV-cfDNA, archived samples from epidemiological cohorts with limited plasma volume are an important source. To establish a cfDNA detection workflow for low plasma volumes, we compared cfDNA purification methods [MagNA Pure 96 (MP96) and QIAamp ccfDNA/RNA] and digital PCR systems (Biorad QX200 and QIAGEN QIAcuity One). Final assay validation included 65 low-volume plasma samples from oropharyngeal cancer (OPC) patients with defined HPV status stored for 2-9 years. MP96 yielded a 28% higher cfDNA isolation efficiency in comparison to QIAamp. Both digital PCR systems showed comparable analytical sensitivity (6-17 copies for HPV16 and HPV33), but QIAcuity detected both types in the same assay. In the validation set, the assay had 80% sensitivity ( n = 28/35) for HPV16 and HPV33 and a specificity of 97% ( n = 29/30). In samples with ≥750 µL plasma, the sensitivity was 85% ( n = 17/20), while in samples with <750 µL plasma, it was 73% ( n = 11/15). Despite the expected drop in sensitivity with decreased plasma volume, the assay is sensitive and highly specific even in low-volume samples and thus suited for studies exploring HPV-cfDNA as an early HPV-OPC detection marker in low-volume archival material.IMPORTANCEHPV-OPC has a favorable prognosis compared to HPV-negative OPC. However, the majority of tumors is diagnosed after regional spread, thus making intensive treatment necessary. This can cause lasting morbidity with a large impact on quality of life. One potential method to decrease treatment-related morbidity is early detection of the cancer. HPV cfDNA has been successfully used for therapy surveillance and has also been detected in pre-diagnostic samples of HPV-OPC patients. These pre-diagnostic samples are only commonly available from biobanks, which usually only have small volumes of blood plasma available. Hence, we have developed a workflow optimized for small-volume archival samples. With this method, a high sensitivity can be achieved despite sample limitations, making it suitable to conduct further large-scale biobank studies of HPV-cfDNA as a prognostic biomarker for HPV-OPC., Competing Interests: T.W. serves on advisory boards for Merck, Sharp & Dohme (MSD). S.L. serves on advisory Boards of MSD, Bristol Myers, Squibb (BMS), and Astra Zeneca (AZ) and has received honoraria from MSD, BMS, AZ, and Merck Serono. D.L.F. has received research funding or in-kind funding from BMS, Calico, Predicine, BostonGene, and NeoGenomics and has received consulting fees from Merck, Noetic, Chrysalis Biomedical Advisors, Arcadia, and Focus. He receives salary support from National Institutes of Health (NIH)/National Institute of Dental and Craniofacial Research (NIDCR) K23 DE029811, NIH/NIDCR R03DE030550, and NIH/National Cancer Institute R21CA267152.

Objective: Persistent infection with high-risk human papillomavirus (HPV) is a key contributor to cervical intraepithelial neoplasia (CIN), but the relation between high-risk HPV genotypes and the location of CIN lesions remains unclear. The aims of this study were to investigate the most frequent biopsy site of CIN lesions in women with different HPV infection and to analyze the biopsy times, CIN frequency, and the clustering of CIN frequency based on 12-o'clock sites and cervical quadrant locations., Materials and Method: We conducted a retrospective study of HPV detection and genotyping at the virology department of our hospital. Colposcopy exams were performed by specialists according to a standardized protocol, and all visually abnormal areas were further biopsied. Pearson chi-squared tests and cluster analyses were implemented to analyze the data., Results: Among 1,381 women enrolled in this study, 933 cases infected with HPV. HPV16, HPV58, and HPV18 were the most common genotypes. The most frequent biopsy site was the 6 o'clock position. The highest frequency of high-grade CIN findings in single-genotype HPV groups was the 6 o'clock position and that for multiple-genotype HPV group was the 12 o'clock location. All CIN clusters were found in the 6 and 12 o'clock biopsy sites, except in the HPV18 group. Quadrant 2 and 4 were clustered in most groups., Conclusions: The 6 and 12 o'clock sites in cervical quadrant 2 and 4 should be targeted during cervical biopsy procedures. These findings can provide clinicians with specific recommendations on the optimal site for CIN biopsy when considering the HPV genotype., (Copyright © 2024, ASCCP.)

Importance: The Ministry of Health, Labour, and Welfare (MHLW) of Japan aggregates human papillomavirus (HPV) vaccination data across Japan for each fiscal year (FY) by age at vaccination. Birth FY (BFY)-specific vaccination coverage remains unknown., Objective: To calculate the BFY-specific vaccination coverage for each FY and the cumulative first-dose coverage for each BFY in Japan, to understand the generation-specific vaccination coverage, and to estimate the cumulative first-dose coverage of each BFY that would be achieved by FY 2028 vs World Health Organization (WHO) targets., Design, Setting, and Participants: In this cross-sectional study, MHLW-published national age-specific HPV vaccination numbers and demographic data for female individuals were used to calculate the BFY-specific first-dose coverage for each FY and the BFY-specific cumulative first-dose coverage. It was assumed that the BFYs 2007 to 2012 vaccination coverage in FY 2023 to 2028 would remain the same as the vaccination coverage of the same grade in FY 2022 to estimate the cumulative first-dose coverage that would be achieved by FY 2028. Data analysis was performed from December 2023 to January 2024., Exposure: Two MHLW policy changes were the government's suspension of proactive recommendation for HPV vaccination in June 2013 and the government's resumption of proactive recommendation for HPV vaccination in April 2022., Main Outcomes and Measures: The primary outcome was generation-specific vaccination coverage among female individuals born in BFYs 1994 to 2010 in FYs 2010 to 2022, calculated using reconfigured published data., Results: In this study of vaccination data for 9 414 620 female individuals, the generation-specific vaccination coverage was 71.96% for the vaccination generation (BFYs 1994-1999), 4.62% for the vaccine-suspension generation (BFYs 2000-2003), 16.16% for the generation that received information individually (BFYs 2004-2009), and 2.83% for the vaccine-resumed generation (BFY 2010). HPV routine vaccination coverage was extremely low in BFYs 2000 to 2010 (0.84%-25.21%) vs BFYs 1994 to 1999 (53.31%-79.47%). The cumulative first-dose coverage that was estimated to be achieved in the vaccine-resumed generation by FY 2028 plateaued at 43.16%., Conclusions and Relevance: Even after the resumption of MHLW's proactive recommendations, HPV vaccination coverage has only minimally recovered in Japan. The cumulative first-dose coverage that was estimated to be achieved in the vaccine-resumed generation by FY 2028 is below the WHO target. These findings reveal that stronger cervical cancer control measures are required, particularly for the vaccine-resumed generation, which will plateau at approximately one-half the WHO target values.

Background: A persisting high-risk human papillomavirus (HR-HPV) infection is causal for cervical cancer; however, there is limited population-based data on the prevalence of HPV infections in Germany. We assessed the age and type-specific HPV prevalence, and associated risk factors in HPV unvaccinated women aged 30 and above., Methods: The MARZY prospective population-based cohort study was conducted between 2005 and 2012 in Mainz and Mainz-Bingen, Germany. Eligible women were randomly recruited from population registries and invited for cervical cancer screening (n = 5,275). A study swab (liquid-based cytology) was taken and HPV testing was performed with GP5+/6 + polymerase chain reaction (PCR) followed by genotyping. We assessed HPV types as HR-HPV, 'moderate' risk and low-risk (LR-HPV). Logistic regression was performed to identify factors associated with HPV infection, stratified by HPV types., Results: 2,520 women were screened with a valid PCR result. Overall HPV prevalence was 10.6% (n = 266), with 6.5% HR-HPV positive (n = 165), 1.5% 'moderate' risk type (n = 38) and 3.3% LR-HPV type (n = 84) positive. 8.9% had a single infection (n = 225) and 1.6% had multiple types (n = 41). The most common HR-HPV types were 16, 56, 52 and 31 and LR-HPV 90 and 42. Of 187 HR-HPV infections detected (among 165 women), 55.1% (n = 103) were with HPV types not covered by available bivalent or quadrivalent HPV vaccines. About 23% (n = 43) were of types not covered by the nonavalent vaccine (HPV 35, 39, 51, 56, 59). The HR and LR-HPV prevalence were highest in the age group 30-34 years (HR 9.8%, 'moderate' risk 3.0% and LR 5.6%), decreasing with increasing age. HR-HPV prevalence in women with normal cytology was 5.5%. In women with a high-grade squamous intraepithelial lesion (HSIL), prevalence was 66.7%. Women currently not living with a partner and current smokers had increased chances of an HR-HPV infection., Conclusion: The overall population-based HPV prevalence was relatively high. An important share of prevalent HR-HPV infections constituted types not covered by current HPV vaccines. With the advent of HPV screening and younger vaccinated cohorts joining screening, HPV types should be monitored closely, also in older women who were not eligible for HPV vaccination., (© 2024. The Author(s).)

Background: One of the goals of the President's Cancer Panel was to maximize access to human papillomavirus (HPV) vaccination through expansion of alternative settings for receiving the vaccine, such as in public health settings, schools, and pharmacies., Methods: In a cross-sectional analysis, we utilized the National Immunization Survey-Teen data from 2014 to 2020 (n = 74,645) to describe trends and factors associated with HPV vaccine uptake in private, public, and alternative settings. We calculated annual percent change (APC) between 2014 and 2020, estimating rate of HPV vaccine uptake across settings. Using multinomial logistic regression, we estimated the odds of receipt of HPV vaccine in public health settings and other alternative settings compared to private healthcare settings, adjusting for sociodemographic covariates., Results: We found a 5 % annual increase in the use of private facilities between 2014-2018 (APC = 5.3; 95 % CI 3.4, 7.1), and almost 7 % between 2018-2020 (APC = 6.7; 95 % CI 1.4, 12.3). Adjusted multinomial logistic regression analyses found that odds of receiving vaccinations at a public facility vs. a private facility increased almost two times for adolescents living below poverty (aOR = 1.82, 95 % CI: 1.60, 2.08) compared to above poverty. Additionally, adolescents without physician recommendations had lower odds of receiving vaccines at public versus private facilities (aOR = 1.75, 95 % CI: 1.44, 2.12). Finally, odds of receiving HPV vaccines at public facilities vs. private facilities decreased by 33 % for White adolescents (aOR = 0.67, 95 % CI: 0.57, 0.78) versus Black adolescents., Conclusions: Sociodemographic factors such as race, and socioeconomic factors such as poverty level, and receipt of physician HPV recommendations are associated with receiving the vaccine at private settings vs. public health facilities and alternative settings. This information is important in strengthening alternative settings for HPV vaccine uptake to increase access to the vaccine among disadvantaged individuals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The vaginal microbiome (VM) is associated with human papillomavirus (HPV) infection and progression, but a thorough understanding of the relation between HPV infection, and VM needs to be elucidated. From August to December 2022, women who underwent routine gynecological examinations were screened for HPV infection. The distribution of HPV variants and clinical characteristics were collected. Then, a total of 185 participants were enrolled and divided into HPV-negative (HC), high-risk HPV (H), low-risk HPV (L), multiple high-risk HPV (HH), and mixed high-low risk HPV (HL) groups. Samples were collected from the mid-vagina of these 185 participants and sent for 16S rDNA sequencing (V3-V4 region). Among 712 HPV-positive women, the top 3 most frequently detected genotypes were HPV52, HPV58, and HPV16. Among 185 participants in the microbiology study, the β diversity of the HC group was significantly different from HPV-positive groups ( P < 0.001). LEfSe analysis showed that Lactobacillus iners was a potential biomarker for H group, while Lactobacillus crispatus was for L group. Regarding HPV-positive patients, the α diversity of cervical lesion patients was remarkably lower than those with normal cervix ( P < 0.05). Differential abundance analysis showed that Lactobacillus jensenii significantly reduced in cervical lesion patients ( P < 0.001). Further community state type (CST) clustering displayed that CST IV was more common than other types in HC group ( P < 0.05), while CST I was higher than CST IV in H group ( P < 0.05). Different HPV infections had distinct vaginal microbiome features. HPV infection might lead to the imbalance of Lactobacillus spp. and cause cervical lesions., Importance: In this study, we first investigated the prevalence of different HPV genotypes in south China, which could provide more information for HPV vaccinations. Then, a total of 185 subjects were selected from HPV-negative, high-risk, low-risk, multiple hr-hr HPV infection, and mixed hr-lr HPV infection populations to explore the vaginal microbiome changes. This study displayed that HPV52, HPV58, and HPV16 were the most prevalent high-risk variants in south China. In addition, high-risk HPV infection was featured by Lactobacillus iners , while low-risk HPV infection was by Lactobacillus crispatus . Further sub-group analysis showed that Lactobacillus jensenii was significantly reduced in patients with cervical lesions. Finally, CST clustering showed that CST IV was the most common type in HC group, while CST I accounted the most in H group. In a word, this study for the first time systemically profiled vaginal microbiome of different HPV infections, which may add bricks to current knowledge on HPV infection and lay the foundation for novel treatment/prevention development., Competing Interests: W.L. and S.J. are employed by Shanghai Biotecan Pharmaceuticals Company. The other authors declare no conflict of interest.

Introduction: Human papillomavirus (HPV) vaccination rates among females are lower than the World Health Organization target and vaccination rates specifically among adult females are even much lower., Methods: We systematically evaluated individual socioeconomic and health-related characteristics associated with HPV vaccination initiation and vaccination series completion among adult females (PROSPERO: CRD42023445721). We performed a literature search on December 14, 2022, and supplemented the search on August 1, 2023. We pooled appropriate multivariable-adjusted results using an inverse variance random-effects model and expressed the results as odds ratios with associated 95 % confidence intervals. A point pooled significantly increased/decreased odds of 30-69 % was regarded to be strongly associated, and ≥ 70 % was very strongly associated., Results: We included 63 cross-sectional studies. There were strongly increased odds of vaccination initiation among White women compared with Black or Asian women, and those with higher education, health insurance, a history of sexually transmitted infection (STI), receipt of influenza vaccination in the preceding year, not married/cohabiting, not smoking, using contraception, and having visited a healthcare provider in the preceding year. We observed very strongly increased odds of vaccination initiation among those younger and having been born in the country of study. Similarly, there were strongly increased odds of completing the vaccination series for the same variables as initiating vaccination, except for higher education, prior STI, smoking and contraception use. Additional variables associated with strongly increased odds of vaccination series completion not seen in initiation were higher annual household income, being lesbian/bisexual, and having a primary care physician. We observed very strongly increased odds of vaccination series completion similar to vaccination initiation but including for White compared with Black women, higher education, and prior cervical cancer screening., Conclusions: These individual characteristics may be the key to identifying women at increased risk of not being vaccinated against HPV and could inform targeted messaging to drive HPV vaccination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This study received no funding., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To illustrate an evidence-, theory- and person-based approach to codesign the COMMUNICATE films that support parental decision-making about the human papillomavirus (HPV) vaccine for their teenagers., Design: Codesign study., Setting: Localities covered by two immunisation teams in London and the south-west of England., Methods: The intervention planning phase involved combining evidence from a literature review with qualitative interview data to identify barriers and facilitators to HPV vaccine uptake, as well as design features that should be incorporated within the COMMUNICATE films. The intervention development phase involved identifying guiding principles for the COMMUNICATE films, mapping behaviour change techniques onto the behaviour change wheel and codesigning the COMMUNICATE films. Feedback from users informed modifications to maximise acceptability and feasibility and to support behaviour change., Results: The primary and secondary evidence highlighted important content to include within the COMMUNICATE films: emphasise the benefits of the HPV vaccine, provide transparent information about the safety profile and side effects and emphasise the universality and commonality of HPV infection. A series of scripts were used to guide 4 film shoots to create the content in multiple community languages with 16 participants, including vaccine-hesitant, ethnically diverse parents and professionals. Overall, participants were positive about the films. Potential messengers and ways the films could be distributed, identified by parents, include local social media networks or text messages from general practices. The need for information about the HPV vaccine to be shared by schools ahead of consent being sought was also raised., Conclusions: By using an integrated approach to intervention development, this study has begun to address the need for an intervention to support vaccine-hesitant, ethnically diverse parents' decision-making about the HPV vaccination programme. A future study to codesign, implement and evaluate a communication strategy for the COMMUNICATE films is planned., Competing Interests: Competing interests: AF is a member of the Joint Committee on Vaccination and Immunization and was, until December 2022, chair of the WHO European Technical Advisory Group of Experts on Immunization committee. The other authors have no relevant conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Despite documented mental illness-related disparities in cervical cancer screening and incidence, insufficient data exist on differences in cervical cancer prevention strategies, such as human papillomavirus (HPV) vaccination. We aimed to investigate the association of mental illness and neurodevelopmental conditions among girls and their parents with uptake of HPV vaccination in Sweden., Methods: This population-based cohort study was based on the Swedish school-based HPV vaccination programme, which offers the first vaccine dose to girls aged 10-13 years, with a second dose offered within 12 months. We identified all girls born between Jan 1, 2002, and March 1, 2004, using the Swedish Total Population Register-ie, those eligible for two vaccine doses in the vaccination programme from its initiation in autumn 2012, to March, 2019. Nationwide Swedish register data (National Patient Register, Prescribed Drug Register, HPV Vaccination Register, National Vaccination Register, Total Population Register, Multi-Generation Register, Longitudinal Integrated Database for Health Insurance and Labour Market Studies, Education Register, National Cervical Screening Registry, and Cancer Register) were used to define individual and parental mental health conditions, including mental illness and neurodevelopmental conditions (defined by a clinical diagnosis and prescribed psychotropic medication use), HPV vaccine uptake (first and second dose), and sociodemographic and clinical characteristics. The two outcomes were uptake of the first HPV vaccine dose by the girl's 14th birthday and uptake of the second dose by the 15th birthday in relation to individual and parental mental health conditions, calculated using multivariable Poisson regression models., Findings: 115 104 girls were included in the study population. 2211 girls (1·9%) had a specialist diagnosis of any mental health condition. Uptake of the first HPV vaccine dose was 80·7% (92 912 of 115 104) and was lower among girls with versus without any mental health condition (adjusted relative risk 0·89 [95% CI 0·87-0·91]). The diagnosis of autism (0·79 [0·75-0·85]) or intellectual disability (0·78 [0·73-0·83]) were most strongly associated with lower HPV vaccine uptake. Vaccine uptake was also lower among girls with versus those without prescribed use of psychotropic medication (0·93 [0·92-0·95]), with the strongest association observed for antipsychotics (0·68 [0·56-0·82]). Uptake of the second dose was 95·0% (88 308 of 92 912), with no strong associations between uptake and mental health conditions in girls or their parents., Interpretation: Our findings suggest disparities in cervical cancer prevention among girls with mental health conditions, and call for further research to ensure equitable protection., Funding: Swedish Cancer Society., Competing Interests: Declaration of interests KS received research grants, consultancy fees, payment for presentations, and travel support from Merck to the affiliated institution for other research on HPV vaccination. JW and ALF received grant support from Merck to the affiliated institution. ALF also received grant support from Janssen Pharmaceutica to the affiliated institution. UV received payment for keynote lectures at the International Society for Traumatic Stress Studies, European Psychiatric Association, and European Congress on Obesity conferences; and grants from European Research Council, Nordforsk, and Horizon2020 to the affiliated institution. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Human papillomaviruses (HPVs) are well-known causative agents of several cancers, yet selective therapies remain under investigation. Nanoparticles, for instance, are emerging as promising solutions to enhance the delivery and efficacy of therapeutic approaches. Despite the increasing number of nanotherapies offering advantages over current treatments, only one has advanced to clinical trials. This review highlights recent advances in nanotherapies for HPV-associated cancers, focusing on the delivery of small molecules, gene-targeted therapies, and vaccines. Some of the challenges faced in nanotherapies translation for clinical application are discussed, emphasizing the most used preclinical models that fail to accurately predict human responses, thereby hindering proper evaluation of nanotherapies. Additionally, we explore and discuss alternative promising new preclinical models that could pave the way for more effective nanotherapeutic evaluations., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Human papillomavirus (HPV) infection and menopause entail a considerable impairment in health-related quality of life (HRQoL). The objective of the present study was to analyze the impact of the menopause status on HRQoL in women with HPV infection., Methods: A cross-sectional, nationwide, multicenter sample of women with HPV infection was conducted throughout clinics of gynecology representative of the Spanish population with regard to age, geographic density, and autonomous regions. Demographic and clinical characteristics and the specific HPV-QoL questionnaire score with its domains were compared according to reproductive status: premenopausal and peri-/postmenopausal. Correlation with other validated patient-reported outcomes measurements was also tested, including General Health Questionnaire-12 (GHQ-12), Female Sexual Function Index (FSFI), and Hospital Anxiety and Depression Scale (HADS)., Results: A sample of 1,016 noninstitutionalized women, aged 18-80 y, was recorded, 191 (18.8%) peri-/postmenopausal and 825 (81.2%) premenopausal. Total HPV-QoL scoring was significantly lower in peri-/postmenopausal (38.8, 95% CI [35.2-42.4]) compared to premenopausal (46.4, 95% CI [45.0-47.8]) women, and also in every domain of the scale (P < 0.05), except in social well-being and health domains, with a small effect size of 0.39. In women with sexual dysfunction according to FSFI, adjusted total scoring and domains sexuality, general well-being, and psychological well-being scored significantly higher in premenopause women (P < 0.01), although the magnitude of differences were of small to moderate size., Conclusions: HRQoL was impaired during menopause in women with HPV infection according to HPV-QoL questionnaire. The sexuality domain was the most differentiating dimension between these populations., Competing Interests: Financial disclosures/conflicts of interest: This work was sponsored by the Asociación Española De Patología Cervical y Colposcopia (AEPCC). No financial or editorial support was provided except for a review of the English, conducted by Javier Calvo-Torres. Javier Rejas is an independent member of the EACCOS Research Group, Universidad Autónoma de Madrid, Madrid, Spain, and declares no conflicts of interest as a consequence of participating in this study. Isabel Gippini gave a lecture at GINEP en La Coruña about quality of life in menopause, paid for by Theramex, and had accommodations paid for by Dynamesh where she gave a lecture about robotic colposacropexy. The other authors have nothing to disclose., (Copyright © 2024 by The Menopause Society.)

Bovine Papillomaviruses (BPVs) constitute a diverse group within the Papillomaviridae family, playing a crucial role in bovine health and economic considerations. This study investigates the dynamics of vertical transmission of BPV in cattle, focusing on five cows and their reproductive tissues, as well as three gravid cows and their fetuses. DNA and RNA samples were extracted from the warts, fetal skin, placenta, uterus, ovary, and blood of cows, as well as the skin and blood of fetuses. Polymerase Chain Reaction (PCR) targeted BPV types 1-6 and 8-14, was assessed in both cows and fetuses. Additionally, Reverse Transcription PCR (RT-PCR) examined BPV-2 E5 oncogene expression in the skin and reproductive sites of mother cows and fetuses. Our findings unveil a rich diversity of BPV types, including BPV-2, 3, 9, 10, 12, and 14, present in both maternal and fetal tissues. Intriguingly, certain types, namely BPV-4, 6, 8, and 11, were exclusively identified in maternal tissues A higher diversity of BPVs was observed in cow warts, followed by cow blood, fetal blood, and fetal skin. Strikingly similar BPV types in gravid cow blood and fetuses suggest primary dissemination through the bloodstream and transmission via the placenta, though detected in lower numbers in cow uterus and ovary. Histopathological analysis revealed no abnormalities in the reproductive tissues despite the presence of BPV. However, in one bladder sample from a cow that did not consume bracken fern, urothelial neoplasia in situ was observed. The study extends beyond detection, exploring the expression of the BPV-2 E5 oncogene in fetal tissues, providing insights into potential cell implications. Comparative analyses with previous studies highlight the uniqueness of our investigation, encompassing a broader array of BPV types in the gravid cows and their fetuses. The findings not only establish a foundation for further investigations into the mechanisms of vertical transmission but also highlight the need for targeted interventions and surveillance strategies to mitigate potential health risks associated with specific BPV types., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Full-thickness high-grade squamous intraepithelial lesions (HSIL) are precursors of invasive cervical squamous cell carcinoma (SCC). The World Health Organization and Lower Anogenital Squamous Terminology Standardization Project for human papilloma virus (HPV)-associated lesions divide full-thickness HSIL of the cervix into thin HSIL with thickness of 1 to 9 cell layers and the typical full-thickness HSIL of >10 cell layers. Although HPV oncogene transcripts and p16ink4a overexpression, as markers of transforming HPV infection, are detectable in thin HSIL, the biological significance of thin HSIL in cervical carcinogenesis remains poorly understood. To further characterize thin HSIL, we performed a comparative study of chromosomal copy number variations (CNV), an analysis of dysregulated genes present in the segments with CNV, and a generalized genetic complexity calculation for 31 thin HSIL, 31 thick HSIL, 24 microinvasive SCC (pT1a SCC), and 22 highly invasive SCC samples. Thin HSIL share various CNV and specific dysregulated gene pathways with thick HSIL and invasive SCC. Thin HSIL exhibited an average CNV of 11.6% compared with 14.1% for thick HSIL, 15.5% for pT1a SCC, and 26.6% for highly invasive SCC. The CNV included gains at 1q and 3q (40% and 43%, respectively), partial loss of 3p, and loss of chromosomes 11 (18%), 16 (50%), 20 (35%), and 22 (40%). Pathways affected solely in thin HSIL were those enhancing immune evasion and primarily involved the (interleukin) IL6, IL21, and IL23 genes. ILs are transiently upregulated in response to infection and play a crucial role in mounting antitumor T-cell activity. Deregulation reflects an attempt by the HPV to evade the initial immune response of the host. The primary pathways shared by thick HSIL and invasive SCC were interactions between lymphoid and nonlymphoid cells, NOTCH2 signaling, tight junction interactions (primarily of the claudin family), and FGR2 alternative splicing. Our results show that thin HSIL carry similar genetic changes as thick HSIL and SCC, indicating that thin HSIL are true precursor lesions that can progress to thick HSIL and SCC., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare no conflict of interest.

Context.—: There have been exceedingly few reports of epidermodysplasia verruciformis (EV) or EV-like lesions in the vulva. We describe the first observation of vulvar lesions displaying synchronous EV-like histology and conventional high-grade squamous intraepithelial lesion (HSIL), a finding hitherto unreported in medical literature., Objectives.—: To describe this novel vulvar lesion with hybrid features of HSIL and EV, attempt to confirm the hypothesis of coinfection with α and β human papillomavirus (α-HPV and β-HPV) genotypes, and describe relevant underlying genetic mutations., Design.—: Cases were retrospectively selected from our institutional archive. Detailed review of clinical information, histologic examination, and whole genome sequencing (WGS) were performed., Results.—: Five samples from 4 different patients were included. Three of 4 patients had a history of either iatrogenic immune suppression or prior immune deficiency, and all 3 featured classic HSIL and EV changes within the same lesion. One patient had no history of immune disorders, presented with EV-like changes and multinucleated atypia of the vulva, and was the sole patient without conventional HSIL. By WGS, several uniquely mappable reads pointed toward infection with multiple HPV genotypes, including both α-HPVs and β-HPVs. Mutations in genes implicated in cell-mediated immunity, such as DOCK8, CARMIL2, MST1, and others, were also found., Conclusions.—: We provide the first description of vulvar lesions harboring simultaneous HSIL and EV features in the English-language literature, a phenomenon explained by coinfection with α-HPV and β-HPV genotypes. The finding of EV-like changes in a vulvar specimen should prompt assessment of the patient's immune status., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

The microbial community has a profound effect on the host microenvironment by altering metabolites. Persistent high-risk human papillomavirus (HRHPV) infection has been implicated as contributors to the initiation and progression of cervical cancer, but the involved mechanisms are unknown. Assessing the metabolic profile of the cervicovaginal microenvironment has the potential to reveal the functional interactions among the host, metabolites and microbes in HRHPV persistence infection and progression to cancer. The vaginal swabs of women were collected and divided into three groups according to the HPV HybridenPture DNA test (HC2). The participants, include 9 who were categorized as HPV-negative, 8 as positive for HPV16, and 9 as positive for HPV18. 16S rRNA gene sequencing and metabolomics analyses were applied to determine the influence of the vaginal microbiota and host metabolism on the link between HPV and cervicovaginal microenvironment. These findings revealed that HRHPV groups have unique metabolic fingerprints that distinguish them from heathy controls. We showed that HRHPV affects changes in microbial metabolic function, which has important implications for the host. Our study further demonstrated metabolite-driven complex host-microbe interactions and assist in understanding the alterations in the HRHPV-induced cervicovaginal microenvironment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a recently described neoplasm entity that presents only in the sinonasal tract. Histologically, it displays features of both a surface-derived carcinoma and a salivary gland carcinoma, and is associated with high-risk HPV, specifically HPV type 33. Whereas majority of the cases display high-grade histologic features, HMSC paradoxically behaves in a relatively indolent fashion. It is important and meaningful to distinguish HMSC from other histopathologic mimickers as the clinical features and management are distinctive. A 64-year-old woman presented having intermittent left-side epistaxis and progressive nasal obstruction. A well-defined, solitary, friable mass with an irregular surface that easily bled upon contact was found in the posterior part of the left nasal cavity. Endoscopic excision of the tumor which was originated from left nasal septum was done and the tumor was confirmed as HMSC. After surgery, definitive radiotherapy was performed in 28 fractions. HMSC is a histopathological type that has been rarely reported so that we report this case with literature review., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Patients with pathogenic variants in the GATA Binding Protein 2 ( GATA2 ), a hematopoietic transcription factor, are at risk for human papillomavirus-related (HPV) anogenital cancer at younger than expected ages. A female cohort with GATA2 haploinsufficiency was systematically assessed by two gynecologists to characterize the extent and severity of anogenital HPV disease, which was also compared with affected males., Methods: A 17-year retrospective review of medical records, including laboratory, histopathology and cytopathology records was performed for patients diagnosed with GATA2 haploinsufficiency followed at the National Institutes of Health. Student's t -test and Mann-Whitney U test or Fisher's exact test were used to compare differences in continuous or categorical variables, respectively. Spearman's rho coefficient was employed for correlations., Results: Of 68 patients with GATA2 haploinsufficiency, HPV disease was the initial manifestation in 27 (40%). HPV occurred at median 18.9 (15.2-26.2) years in females, and 25.6 (23.4-26.9) years in males. Fifty-two (76%), 27 females and 25 males, developed HPV-related squamous intraepithelial lesions (SIL) including two males with oral cancer. Twenty-one patients developed anogenital high-grade SIL (HSIL) or carcinoma (16 females versus 5 males, (59% versus 20%, respectively, p=0.005) at median 27 (18.6-59.3) years for females and 33 (16.5-40.1) years for males. Females were more likely than males to require >2 surgeries to treat recurrent HSIL (p=0.0009). Of 30 patients undergoing hematopoietic stem cell transplant (HSCT) to manage disease arising from GATA2 haploinsufficiency, 12 (nine females, three males) had persistent HSIL/HPV disease. Of these nine females, eight underwent peri-transplant surgical treatment of HSIL. Five of seven who survived post-HSCT received HPV vaccination and had no or minimal evidence of HPV disease 2 years post-HSCT. HPV disease persisted in two receiving immunosuppression. HPV disease/low SIL (LSIL) resolved in all three males., Conclusion: Females with GATA2 haploinsufficiency exhibit a heightened risk of recurrent, multifocal anogenital HSIL requiring frequent surveillance and multiple treatments. GATA2 haploinsufficiency must be considered in a female with extensive, multifocal genital HSIL unresponsive to multiple surgeries. This population may benefit from early intervention like HSCT accompanied by continued, enhanced surveillance and treatment by gynecologic oncologists and gynecologists in those with anogenital HPV disease., Competing Interests: PS, also add participated in an Endometriosis Research Day at the Open Endoscopy Forum Cambridge, Massachusetts, and reviewed a book proposal on endometriosis for Elsevier. Outside of this work, PS has received royalties from UpToDate for a section about acute pelvic pain, from Frontiers in Reproductive Health as Specialty Chief Editor, Gynecology, and participated in an AbbVie advisory board. PS also participated in an Endometriosis Research Day at the Open Endoscopy Forum Cambridge, Massachusetts, and reviewed a book proposal on endometriosis for Elsevier. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Dancy, Stratton, Pichard, Marciano, Cowen, McBride, Van Doorslaer, Merideth, Salmeri, Hughes, Heller, Parta, Hickstein, Kong, Holland and Zerbe.)