Although HPV infection is obligatory for almost all cases of cervical cancer (CC), other risk factors can promote the progression of cervical cancer. In this context, the expression of human endogenous retroviruses (HERVs) in the development of CC has been investigated. In this study, the expression status of HERV-E env transcripts was analyzed in 111 cervical biopsies, including 35 cervical cancer samples, 20 precancerous lesions, and 56 normal samples. Real-time PCR with specific primers was used to quantify the relative expression of HERV-E env, HPV 16 and 18 E6/E7 genes, and GAPDH as a normalization control. Our results indicated an increase in the expression of HERV-E env, and the difference was statistically significant in the cancer group compared to the precancerous group (1.5-fold change) (P = 0.031). In HPV 16 or 18-infected patients, a higher mean value of HERV-E env mRNA was also found in the cancer group than in the precancerous group. ROC curve analysis showed a significant difference in env expression between precancerous and cancerous lesions in all patients analyzed (P = 0.015) and in a group of patients infected with HPV 16 or 18 genotypes (P = 0.023). In addition, there was a positive correlation between the higher expression of HERV-E env mRNA with E7 (R = 0.34, P = 0.016) and age (R = 0.35, p = 0.016) in HPV 16-infected patients. In conclusion, our study found a possible association between HERV-E env expression and cervical cancer, as HERV-E is actively transcribed during the progression of cervical lesions. Future studies on the potential interaction of HERV-E env with HPV 16 E7 oncoprotein are likely to elucidate common signaling pathways in the progression of cervical cancer and other HPV-related malignancies.

Human papillomavirus genotype distribution in cervical intraepithelial neoplasia grade 2+ from childhood vaccinated women: The Trial23 cohort study.

Objective This study aimed to evaluate the pathological outcomes of conisation with or without subsequent hysterectomy in patients diagnosed with adenocarcinoma in situ (AIS) and grade 3 cervical intraepithelial neoplasia (CIN3), emphasizing the impact of margin status on residual disease and recurrence risk. Methods A retrospective analysis was conducted on patients diagnosed with AIS and CIN3 who underwent loop electrosurgical excision procedure (LEEP) or cold-knife conisation (CKC) between January 2012 and December 2022. The pathological findings of conisation and subsequent hysterectomy, as well as recurrence rates in patients managed conservatively, were analyzed. Patients were followed for a minimum of 3 years, with recurrence defined as the detection of cervical intraepithelial neoplasia (CIN) through colposcopy. Results A total of 387 patients were included: 107 with AIS and 280 with CIN3. Hysterectomy was performed in 72.9% of AIS patients and 49.3% of CIN3 patients after conisation. Positive conisation margins were associated with a higher likelihood of residual disease in hysterectomy specimens, especially in cases with cervical canal involvement in AIS (70.0%) and with combined endo/ectocervical and canal margin involvement in CIN3 (60.0%). In multivariable logistic regression analysis adjusting for age, HPV status, and conisation technique, cervical canal margin involvement was independently associated with positive hysterectomy pathology in AIS (OR 6.962, 95% CI 1.393–34.794; p = 0.018), whereas endo/ectocervical margin involvement was the independent predictor in CIN3 (OR 6.790, 95% CI 1.683–27.387; p = 0.007). The preoperative HPV infection rate was lower in AIS than in CIN3 (88.8% vs 97.1%, p = 0.002). Conclusion While hysterectomy is recommended for AIS with positive margins, conisation alone may be a safe alternative for selected patients without involvement of the cervical canal margin.

Cervical cancer is the fourth most common malignancy among women worldwide, with persistent high-risk HPV infection as its necessary cause. The World Health Organization (WHO) has set the “90-70-90” targets for 2030 to accelerate cervical cancer elimination. Given China’s large population, progress in vaccine accessibility, coverage, and long-term protection will have a major impact on global control efforts. Despite advances in vaccine development, approval, and policy innovation, challenges remain, including uneven coverage, limited long-term follow-up, low male vaccination uptake, and financial sustainability. This review synthesizes evidence on vaccine development, clinical evaluation landscape, policy practice, and HPV vaccination coverage in China to identify key barriers to implementation and outline strategic directions for achieving sustainable high coverage. It aims to inform the design of a unified national immunization program in China and provide lessons for cervical cancer prevention in other low- and middle-income countries.

PurposeThis study investigated the association between periodontitis and oral HPV infection, while exploring the role of oral bacterial microbiota diversity.Methods and MaterialsData from 4,685 adults in the NHANES 2009–2012 cycles were analysed. Periodontitis was defined based on clinical examination, and oral HPV infection was identified using PCR from oral rinse samples. Multivariable logistic regression models were employed to assess the relationship, adjusting for body mass index (BMI), age, sex, ethnicity, education, smoking, alcohol consumption, daily dental flossing, and history of systemic diseases. Subgroup analyses were stratified by age, sex, and education. Mediation analysis was performed to evaluate whether the oral microbiome acts as a mediator in the relationship between periodontitis and oral HPV infection.ResultsNo statistically significant overall association was found between periodontitis and oral HPV infection (P > 0.05). However, females with moderate to severe periodontitis exhibited increased odds of oral HPV infection (P < 0.05). Oral HPV infection was associated with greater microbial diversity (higher operational taxonomic units [OTUs]). No significant mediating effect of the oral microbiome was observed.ConclusionModerate to severe periodontitis appears to be associated with higher odds of oral HPV infection in females. These findings highlight the potential relationship between oral health, microbial diversity, and oral HPV infection.Clinical ImplicationIn the general population, periodontitis does not appear to be a major risk factor for oral HPV; however, female with moderate to severe periodontitis and individuals with higher educati-on showed increased odds of oral HPV infection, suggesting that maintaining periodontal health may be particularly important for HPV related risk management in these subgroups.

Background/Objective: High-risk Human papillomavirus (hrHPV) is the leading cause of premalignant lesions and cervical cancer (CC), affecting disproportionally women living with HIV. Mozambique is among the countries with a heavy triple-burden of HIV, hrHPV infections and CC which accounts for more than 5300 new cases and 3800 deaths each year. In this study, we assessed the age-specific distribution and factors associated with hrHPV and cervical lesions among HIV-positive and -negative women from HPV-ISI (HPV Innovative Screening Initiative) study in Maputo, Mozambique. Methods: This cross-sectional study included 1248 non-pregnant women aged ≥18 years who attended CC screening at the DREAM Sant’Egídio Health Centre between July 2021 and April 2022. Screening involved visual inspection with acetic acid (VIA) and high-risk HPV DNA testing. Sociodemographic, lifestyle, and reproductive data were collected through a routine questionnaire. Logistic regression assessed associations between risk factors and hrHPV infection or cervical lesions. Age-specific hrHPV prevalence, partial HPV16/18 genotyping, and abnormal cytology rates were further analyzed by HIV status. Results: The mean age of participants was 43.0 ± 8.6 years. Overall hrHPV prevalence was 28.0%, being higher among HIV-positive women (46.8%) than HIV-negative women (23.8%). Non-16/18 hrHPV genotypes predominated across all age groups. VIA positivity was 11.1%, most frequently involving less than 75% of the cervical area and was more common among younger women (30–45 years) and those living with HIV. Increasing age was associated with lower odds of hrHPV infection (OR = 0.98, 95% CI: 0.97–1.00; p = 0.017), as was higher parity (≥3 deliveries vs. nulliparity: OR = 0.58, 95% CI: 0.36–0.94; p = 0.029). Contraceptive use (OR = 1.65, 95% CI: 1.15–2.38; p = 0.007) and a partially or non-visible squamocolumnar junction (SCJ) (OR = 2.88, 95% CI: 1.74–4.79; p &lt; 0.001) were associated with higher odds of VIA positivity. Conclusions: hrHPV infection and cervical lesions were more frequent in younger and HIV-positive women, highlighting the need for strengthened targeted screening within HIV care services in Mozambique.

Cervical cancer remains a major global public health concern, with persistent infection by high-risk human papillomavirus (hrHPV) types recognized as the primary etiological factor. This review explores the multifactorial nature of the disease, focusing on the complex interplay between host genetic susceptibility and epigenetic alterations that drive cervical carcinogenesis. Evidence from genome-wide association studies (GWAS) is discussed, highlighting the contribution of specific genetic loci, predominantly within the HLA region, to susceptibility to HPV infection and disease progression. In parallel, the review examines the molecular mechanisms by which the viral oncoproteins E6 and E7 promote genetic instability and epigenetic reprogramming, including histone modifications and dysregulation of non-coding RNAs. Particular emphasis is placed on DNA methylation, affecting both the viral genome and host genes such as FAM19A4, CADM1, PAX1, and MAL, as a promising biomarker for triage and detection of high-grade intraepithelial lesions (CIN2+). Finally, the review evaluates currently available methylation-based assays and self-sampling devices, highlighting their potential to enhance diagnostic accuracy and increase participation in cervical cancer screening programs.

Human papillomavirus (HPV) vaccination may eventually eradicate oncogenic vaccine-targeted HPVs but only with a strategy that also protects unvaccinated individuals. We compared the impact of gender-neutral and girls-only vaccination strategies on the indirect and direct protection of unvaccinated and vaccinated young women against HPV16/18 infection using HPV16/18 seropositivity and PCR positivity 3–7 years post vaccination as the outcome measure. A total of 33 Finnish communities were randomized to one of three vaccination strategies: bivalent gender-neutral HPV vaccination (Arm A), girls-only HPV vaccination (Arm B), or control hepatitis B vaccination (Arm C). All individuals born between 1992 and 1995 and residing in these communities (n = 80,272) were invited to participate. Overall, 11,662 males and 20,513 females consented, corresponding to vaccination coverages of 25% and 45%, respectively, in 2007–2009. Between 2010 and 2014, 11,396 cervical samples were collected from 18-year-old participants and subjected to high-throughput PCR-based HPV genotyping. In addition, serum samples were obtained from 8022 unvaccinated women under 23 years of age residing in Arm A (n = 2657), Arm B (n = 2691), or Arm C (n = 2674) communities during the pre-vaccination (2005–2010) and post-vaccination (2011–2016) periods. To assess indirect vaccine effects using PCR and serological outcomes in unvaccinated women, we compared reductions in HPV16/18 prevalence from baseline within the gender-neutral and girls-only vaccination arms, using the control arm as a reference. A significant decrease in seroprevalence between the pre- and post-vaccination periods was detected in the gender-neutral communities for both HPV16 (seroprevalence ratio = 0.64) and HPV18 (0.72), whereas no comparable reductions were observed in the girls-only or control communities. In contrast, a significant reduction in HPV18 PCR-based prevalence from baseline to the post-vaccination period was observed in both the gender-neutral (0.32) and girls-only (0.61) communities. However, after accounting for ratios of seroprevalence rations for secular trends, the corresponding decrease in HPV18 seroprevalence was no longer statistically significant. Vaccine efficacy (VE) in Arm A or Arm B versus Arm C of vaccinated women measured the direct protection of vaccinated women by vaccination strategy. HPV16/18 VEs varied between 89% and 96% with some indication of herd effect against HPV18. Robust effectiveness of vaccination against PCR-confirmed cervical HPV16/18 infections, along with rapid indirect protection against HPV16/18 and HPV18 infections, was evident even with vaccination reaching only 25% and 45% coverage. Our results suggest that vaccine efficacy and herd effect induced by gender-neutral 2vHPV vaccination sets the stage for comprehensive HPV eradication, including the unvaccinated in the vaccinated communities.

Single-dose HPV vaccination in the United States — a multi-modeling analysis

vaccination and screening are the most effective methods for reducing cervical cancer incidence and mortality. With high immunization coverage, there is a potential for changes in the pattern of HPV types circulating in the population, increasing the risk of reduced effectiveness of vaccination programs. Studying genotypic diversity, the prevalence of coinfections, and the interactions of HPV genotypes in different populations is a complex task for determining the oncogenic potential of the pathogen and assessing the effectiveness of vaccination. Study objective. To study the genotypic diversity and prevalence of highly oncogenic HPV types and to conduct an epidemiological assessment of coinfection patterns in patients at risk for sexually transmitted infections (STIs). Materials and methods. From 2005 to 2024, 9,056 patients were examined, including 1,269 women without complaints or clinical manifestations of disease and 751 patients with STIs. They were tested for STIs and identified 12 HPV genotypes. Research methods included PCR, clinical, epidemiological, and statistical methods. Results and discussion. The prevalence of HPV among patients with dermatovenereological profile was 28.4 %. The most common HPV types in patients at risk for STIs are both vaccine-relevant (HPV 16) and non-vaccine-relevant (HPV 31, 33, 35, 45, 56, 58) genotypes of the virus, which is important to consider when developing screening and prevention programs. The prevalence of HPV and STI coinfections was revealed in 74.7 % of cases, including 74.9 % in mycoureaplasmosis. Multiple HPV infection was detected in 15 % of cases, while the most frequent combinations of HPV VCR included genotypes 16, 31, 33, 35 and 56. Based on statistical analysis, competitive interactions are suggested between certain pairs of HPV genotypes.

Persistent infection with high-risk HPV in women can progress to cervical intraepithelial neoplasia and even cervical cancer. This study investigated the cytotoxic and immunomodulatory effects of the TBTCN-TDG photodynamic therapy (PDT) probe in treating HPV-associated cervical lesions. The TBTCN-TDG probe was designed by integrating a donor-acceptor-π-acceptor 1 (D-A-π-A1) structure (TBTCN) with TDG, a moiety targeting Galectin-1, and its targeting ability in HPV-positive SiHa cells was confirmed. The in vitro results demonstrated that TBTCN-TDG combined with light treatment significantly inhibited SiHa cell proliferation, increased apoptosis, and activated immune responses by stimulating dendritic cells, macrophages, and NK cells, through enhanced NF-κB pathway signaling. In vivo, this targeted photosensitizer exhibited substantial therapeutic effects under laser excitation, as evidenced by TUNEL staining, which showed increased apoptosis in lesions. Immune analysis indicated that TBTCN-TDG enhanced NK cell viability and elevated the levels of pro-inflammatory cytokines under laser excitation, such as TNF-α, IFN-γ, and IL-6, confirming immune response activation. In conclusion, the combination of TBTCN-TDG and PDT effectively targets cells infected with HPV, enhances immune responses, and suppresses HPV infection. This suggests a novel therapeutic strategy for photodynamic immunotherapy in patients with cervical high-risk HPV infections.

Human Papillomavirus (HPV) types 16 and 18 are well-established causative agents in cervical cancer. However, the mechanism of malignant transformation remains unclear. Although epithelial-mesenchymal transition (EMT) is regulated by Ca2+ signaling, the functions of transient receptor potential canonical (TRPC) channel in cervical cancer have not been reported. Herein, employing multiple biological approaches, we first revealed that HPV16 and HPV18 infections significantly upregulated the expression of TRPC3 that orchestrated Ras-MAPK and MEK-ERK pathways in the abnormal transformation of cervical epithelial cells. Our transcriptomic sequencing of HPV-infected cervical epithelial cells with depletion of TRPC3 suggested the significant influence of TRPC3 on genes involved in the process of epithelial-mesenchymal transition (EMT). Consistently, inhibition of TRPC3 successfully suppressed HPV-triggered cell viability and EMT. Moreover, we found TRPC3 maintained the viability of HPV - infected cells by suppressing excessive MAPK activation through regulating Ras GTPase - activating protein 4 (RASA4), which was validated by the detection of phosphorylated ERK1/2 (p-ERK1/2).These findings were further confirmed in the HPV-infected female BALB/c mice, highlighting TRPC3 as a key hub in mediating transformation This study advances the knowledge about the Ca2+ signaling-related molecular mechanism underlying HPV-driven malignant transformation. Targeting TRPC3 may have broader therapeutic implications.

Age distribution of high-risk HPV infection and cervical lesions in an unvaccinated adult Brazilian population within an organized screening program

BackgroundHuman papillomavirus (HPV) is the most frequent sexually transmitted virus, with high importance due its oncogenic risk. Previous studies have reported an association between genital dysbiosis and HPV infection in women and also in men co-infected with HPV and HIV. However, it remains to be determined whether penile skin dysbiosis is associated with HPV infection in men who are HIV-negative. This study characterizes the penile skin microbiota (PSM) of HPV-positive and HPV-negative men, hypothesizing that HPV infection is linked to dysbiotic anaerobic-dominated communities.MethodsA cross-sectional study was conducted on 103 sexually active HIV-negative men (70 HPV-negative, 33 HPV-positive). Those who tested HPV-positive were genotyped. The PSM of all samples was analyzed using 16S rRNA sequencing of the V4 region. Alpha and beta diversity were compared. Community State Types (CSTs) were identified using hierarchical clustering. Associations between CSTs and HPV status were tested adjusting for sexual preference.ResultsHPV-positive men exhibited significantly higher microbial richness than HPV-negative men (Chao1 p = .02), particularly those with high-risk genotypes (Chao1 p = .03). Five CSTs were identified, with CST-5 (dominated by Finegoldia and other anaerobes) showing a three-fold higher likelihood of HPV positivity (OR = 3.11, 95% CI: 1.22-8.22) compared to other CSTs. CST-5 also displayed reduced abundance of commensals like Corynebacterium and Staphylococcus.ConclusionsSubclinical HPV infection in HIV-negative men was associated with a dysbiotic PSM, characterized by an increased abundance of anaerobic bacteria alongside with a reduced proportion of facultative anaerobic genera. These findings suggest that PSM composition may influence HPV susceptibility or persistence. Longitudinal studies are needed to explore causality.

To provide the psychometric properties of a novel patient-reported outcomes measurement (PROM), the HPV-Know-Q questionnaire, to assess the HPV-related knowledge in adult women in Spain. After reviewing literature and interviewing women with HPV infection, instrument items and domains were developed. A draft self-administered, multiple-choice questionnaire including relevant questions about HPV infection was pilot tested for comprehension and ease of completion. Psychometric evaluation of the final HPV-Know-Q questionnaire was performed in a cross-sectional, multicenter, validation study conducted in a representative sample of women with HPV infection attending gynecology consultations in Spain. A total of 349 (153 HPV+/196 HPV-) women participated. HPV-Know-Q questionnaire had acceptable metric properties of feasibility, internal consistency and temporal stability (reliability). Construct validity was supported by analyzing item-to-item and item-to-domain correlation and know groups validity, which discriminated the knowledge on HPV of women related to their infection status, abnormal cytology, educational level and prior HPV vaccination. Concurrent validity was demonstrated with a significant correlation with other scales measuring mental and sexual functioning. The HPV-Know-Q questionnaire, a novel and innovative PROM, showed acceptable psychometric properties to evaluate the HPV knowledge in women that support its use in daily medical practice and research.

Despite evidence indicating a comparatively lower incidence of cervical cancer and HPV infection, there is a significant gap in research on their understanding and preventive behaviours. This study aims to reduce the risk of cervical cancer among Muslim women and to bridge existing gaps in cancer prevention strategies. A descriptive, cross-sectional study was conducted using an online questionnaire to collect information from participants. The research aimed to explore socio-demographic characteristics, perceived health concerns, and knowledge, attitudes, and practices related to cervical cancer prevention and screening. The incidence of cervical cancer increases with age. Eight percent of participants reported being diagnosed with cervical cancer. There is a noticeable correlation between age, education level, and cervical cancer diagnosis. All risk factors for cervical cancer were statistically significant (p < 0.001), indicating highly significant differences in awareness levels across the groups. Differences in sources of information were also highly significant (p < 0.001). Additionally, age, marital status, and education were found to be significantly associated with women's understanding and attitudes towards cervical cancer. The study found that educated Muslim women generally have a positive understanding and attitude towards cervical cancer. However, there remains a significant gap that limits women's overall understanding, attitudes, and practices related to the disease. Targeted educational interventions, involving community leaders and health workers, are essential to enhance awareness and improve health practices.

Reference gene evaluation for digital PCR; Applications for RNA biomarker testing in cervical precancer.

Within Host Dynamics of HPV Infection with Cellular Immunity and HPV-infected Dormant Cells Reactivation

Association of CMV, HSV-2, and HPV Infections with Spontaneous Abortion

Clinical impact of glandular involvement in high-grade squamous intraepithelial lesions of the cervix.