Persistent Human Papillomavirus Research Articles

Abstract 4110: Non-classical HLA epigenetic biomarkers associated with concordant cervical and oral HPV infection

Background: Human papillomavirus (HPV) is prevalent in mucocutaneous surfaces, with the persistence of infections causing approximately 5% of human cancers. While HPV presence at one site increases the risk at others and, possibly, increases the risk of cancer(s) in other anatomical sites, this risk varies among individuals despite similar sexual behaviors. Identifying women with high-risk cervical HPV who are also at risk for high-risk oral HPV could help reduce HPV-associated cancers. This study aims to identify methylation biomarkers explaining the risk of concordant high-risk oral HPV in women with cervical high-risk HPV infections. Methods: As part of the Sexual Behavior and HPV Infections in Nigerians in Ibadan study, we conducted a cross-sectional analysis of sexually active women aged 18-45 years in Ibadan, Nigeria. Participants had interviews and clinical examinations and provided oral rinse and cervical swab samples. DNA was extracted and genotyped for HPV using the Anyplex™ II HPV28 assay. An epigenome-wide association study compared DNA methylation patterns between women with high-risk HPV types 16, 18, or 35 detected in both oral and cervical samples (concordant group) and those with high-risk HPV only in cervical samples (control group), matched by age, sexual behaviors, and lifestyle factors. Genome-wide DNA methylation profiling was performed on both sample types (total n=32) using the Infinium Methylation EPIC v2.0 BeadChip. Results: We identified 61 differentially methylated CpG sites in the concordant group, with consistent associations in both cervical and oral samples (Pearson's r = 0.91, p<0.001). Notably, cg11201654 in the promoter region of a non-classical human leukocyte antigen (HLA) gene, HLA-F, was one of the top significant CpGs and showed approximately two-fold hypermethylation in the concordant group in cervical (p = 0.00080) and oral samples (p = 0.00005). Similarly, cg27020253 in the promoter of another non-classical HLA gene, HLA-L, exhibited ∼1.7-fold hypermethylation in both cervical (p = 0.00039) and oral samples (p = 0.00025). These epigenetic modifications suggest that HPV may facilitate immune evasion and persistent infection by suppressing non-classical HLA genes, which are known for modulating immune responses through interactions with natural killer cells. Conclusion: Hypermethylation of non-classical HLA genes may serve as novel biomarkers for identifying women at elevated risk for persistent high-risk HPV infections and related malignancies, offering insights into HPV-mediated immune evasion mechanisms. The consistent methylation patterns across oral and cervical tissues highlight the capacity of HPV to broadly influence host gene regulation. These epigenetic biomarkers could have applications in broader contexts of immunogenetics and cancer risk prediction, potentially refining the stratification of high-risk women. Citation Format: Yinan Zheng, Imran Morhason-Bello, Yishu Qu, Jun Wang, Adeola Fowotade, Adekunle Daniel, Akinyele Adisa, Olutosin Awolude, John Ogunbiyi, Miquel Pavon, Robert Murphy, Isaac Adewole, Deborah Watson-Jones, Lifang Hou. Non-classical HLA epigenetic biomarkers associated with concordant cervical and oral HPV infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4110.

Abstract 6414: Epigenetic signatures of oral HPV-related cancer risk in HIV-positive subjects from Puerto Rico

Abstract Background: Advances in antiretroviral therapy (ART) have not reduced the disproportional incidence and prevalence of oral Human Papillomavirus (HPV) and oropharyngeal cancers in people with HIV (PWH), suggesting ART alone may not fully restore immunity. While DNA methylation is an epigenetic marker strongly linked with aging and cancer, the putative role of epigenetic regulation in HPV-related cancers, particularly in PWH, remains scarce. Methods: We evaluated the methylation profiles from saliva of 16 sexually active PWH (9 HPV-, and 7 HPV+). Oral rinse samples were collected and analyzed for HPV infection and genotyped using the DNA ELISA kit HPV SPF10 and RHA kit HPV SPF10-LiPA25. We measured the genome-wide methylation levels using the Illumina Infinium Methylation BeadChip arrays. We performed enrichment and functional analyses of differentially methylated loci and genes with differential methylation using GREAT and Metascape, respectively. Physical and functional protein-protein interaction networks were constructed using STRINGdatabase. Results: We identified 521 loci with significant differences in the levels of DNA methylation (p<0.1). There was genome-wide hypermethylation in HPV+ participants. Differential methylation analysis associated to cis-regulatory elements showed that 136 loci were associated to one gene, and 381 loci were associated to two or more genes, while four loci were not associated to any genes. Functional analysis of gene-associated loci with differential methylation illustrated significantly impacted biological processes and pathways, including: regulation of G1/S transition of mitotic cell cycle, RAC1 GTPase cycle, oxidative stress response, MAPK cascade, among others (adjusted p<0.05). Additionally, physical and functional interaction networks showed H3C12 as a major hub with 8 interactions with other genes including EGF, RBFOX3, NTRK3, and SIN3B. Conclusion: We found a distinct methylation profile by HPV status associated with cancer-related genes, which may represent novel biomarkers of early identification for HPV-related cancers in PWH in Puerto Rico. Reprogramming DNA methylation patterns may be a safe way to identify, prevent, or treat HPV persistence. Citation Format: Jurelis Torres-Reyes, Mayra S. Haedo-Cruz, Juliana M. Serrano-Rodríguez, Jeannette L. Salgado-Montilla, Maria M. Sánchez-Vázquez, Magaly Martínez-Ferrer, Gabriel Borges-Velez, Josué Pérez-Santiago. Epigenetic signatures of oral HPV-related cancer risk in HIV-positive subjects from Puerto Rico [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6414.

Abstract 3535: Targeting cervical cancer: VC-2 as a vaccine and treatment for HPV infections

Abstract Cervical cancer is a major cause of mortality worldwide and has been attributed to long-lasting (persistent) infections with the human papillomavirus (HPV). Although more than 50 types of HPVs are known the infect the genital tract, fewer than a dozen of them are regularly linked to cervical cancers leading to these types being designated as “high risk” HPVs. The infectious nature of HPVs procures the need for preventative vaccines against cervical cancer, and current vaccines such as Gardasil-9 and Ceravix achieve high efficacy in protection. However, once infections are established, preventative vaccines are inefficient in treating the malignancies. In HPV-associated tumors, the E7 oncoprotein is an ideal target for immunotherapeutic strategies and has been shown to be a likely target to treat cervical cancer. HSV, particularly HSV-2, often coexists with HPV due to similar transmission routes. Studies suggest that HSV infections may enhance the oncogenic effects of HPV by increasing inflammation, immune system modulation, and promoting a more favorable environment for HPV persistence and progression to cancer. Engineered Herpes Simplex Virus Type-1 (HSV-1) has been a promising candidate in treating established cancers and has been shown to be efficacious in improving anti-tumors responses and controlling tumor metastasis. Therefore, in this study, we aim to utilize the engineered HSV-1 strain (VC-2) to treat established cervical cancers and evaluate its efficacy as a prophylactic vaccine. The mice inoculated with the Tal-3 cervical cancer cell line show metastasis in the lungs and formation of large tumors. Moving forward, we would like to conduct therapeutic and prophylactic studies evaluating the reengineered VC-2 towards treating cervical cancer. Citation Format: Mohammed T. Hussain, Robert Ellis, Kiran Fida, Mariano Carossino, Brent A. Stanfield. Targeting cervical cancer: VC-2 as a vaccine and treatment for HPV infections [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3535.

Vaginal microbiota changes of persistent human papillomavirus infection after cervical conization

ObjectiveWe investigated the changes in vaginal microbiota among females with persistent human papillomavirus (HPV) infection following cervical conization in Xinjiang, China.MethodsA total of 108 female participants were enrolled in the study, including 37 HPV-positive females without cervical conization (Group P1), 37 HPV-positive females after cervical conization (Group P2), and 34 HPV-negative females after cervical conization (Group N). DNA was extracted from vaginal secretions, and the V3-V4 regions of bacterial 16S rDNA were amplified and sequenced using NovaSeq technology. The diversity analysis of the bacterial microbiota was conducted using QIIME2 and R software, while the phenotypic analysis was performed with Bugbase software.ResultsLactobacillus was the predominant genus in the vaginal microbiota of women with persistent HPV infection after cervical conization in Xinjiang. Following partial cervical resection, the α-diversity of the vaginal microbiota decreased, particularly among patients who had cleared HPV. Bacterial vaginosis-associated anaerobes were common in the vaginal environment, with their relative abundance increasing in cases of persistent HPV infection. Postoperative persistent HPV infection was found to be correlated not only with pathogens linked to bacterial vaginosis but also with those associated with aerobic vaginitis. Gardnerella and Atopobium, as well as Bifidobacterium and Streptococcus, demonstrated a symbiotic synergy. Both Lactobacillus and Gardnerella exhibited negative correlations with many pathogenic bacteria. Anaerobic and biofilm formation were the most evident phenotypes in individuals with persistent HPV infection after conization.ConclusionThe vaginal microbiota of women with persistent HPV infection following cervical conization is characterized by the coexistence of Lactobacillus dominance and increased microbial diversity. Anaerobic bacteria and biofilm formation may play a significant role in the persistence of HPV infection post-surgery, and the role of Gardnerella in the vaginal flora under an HPV-infected state warrants further study.

THE ROLE OF THE CERVICOVAGINAL MICROBIOME AND LOCAL IMMUNITY IN HUMAN PAPILLOMAVIRUS PERSISTENCE AND PRECANCEROUS CERVICAL CHANGES

Annotation Background. This study provides a detailed review of the interactions between the cervicovaginal microbiome, local immune responses, and human papillomavirus infection outcomes. Methods. A literature review was conducted covering the period from 2015 to 2024 using the PubMed, Scopus, Embase, and Google Scholar databases. The search included keywords such as human papillomavirus, cervicovaginal microbiome, dysbiosis, cytokines, cervical cancer, Boolean operators, and Medical Subject Headings terms for search refinement.Inclusion criteria: Peer-reviewed publications in English and Russian focusing on the cervicovaginal microbiome, immune responses, human papillomavirus persistence, and cervical neoplasia; observational studies, clinical trials, and reviews. Exclusion criteria: Non-peer-reviewed sources, gray literature, and studies unrelated to microbiome-immune system interactions or human papillomavirus outcomes. Results. Lactobacillus species, particularly L. crispatus, play a key role in maintaining an acidic vaginal environment that modulates local immunity and promotes human papillomavirus clearance. Dysbiosis, characterized by an overgrowth of Gardnerella, Prevotella, and Sneathia, leads to inflammation, disruption of the epithelial barrier, and human papillomavirus persistence. Hormonal fluctuations and environmental factors influence these processes, determining infection outcomes and disease progression. Conclusion. The cervicovaginal microbiome and local immunity are integral to human papillomavirus pathogenesis and cervical cancer prevention.

Optimizing the Follow-Up Interval After Successful Cold Knife Conization of CIN3: A 10-Year Retrospective Cohort Study.

This study was conducted to identify the risk of residual or recurrent high-grade squamous intraepithelial lesions or worse (HSIL+) in patients with successful conization and to develop a customized management strategy. This retrospective study included 939 patients who underwent cold knife conization (CKC) for cervical intraepithelial neoplasia 3 at a hospital in China between January 1, 2013 and December 31, 2020. Demographic characteristics and test results were obtained before and 6, 12, and 24 months after CKC and annually thereafter. Human papillomavirus (HPV) persistence was defined as HPV positive at both 6 and 12 months after CKC, and the primary endpoint was residual or recurrent HSIL+ after CKC. The mean follow-up period was 68.8 months. In total, 61 (6.5%) patients had HPV persistence, and 19 (2.0%) had residual or recurrent HSIL+. The risk of residual or recurrent HSIL+ was increased in patients with HPV infection at 6 months (hazard ratio [HR], 84.6; 95% confidence interval [CI], 11.2-641) and 12 months (HR, 214; 95% CI, 28.1-1625) after CKC, and HPV persistence after CKC (HR, 244; 95% CI, 32.2-1854). Comparing two different colposcopic referral criteria for HPV persistence and HPV positive 6 months post-CKC, substantially fewer colposcopies were performed per case of residual or recurrent HSIL+ detected in patients with HPV persistence after CKC (3.39 vs. 8.28). The risk of residual or recurrent HSIL+ was higher in patients with HPV persistence after CKC. In patients with negative margins, extending the follow-up interval to 12 months may reduce the number of HPV tests and colposcopy referral rates while maintaining HSIL+ detection.

Association of HPV16/18 genotype infection with the Silva pattern classification system in human papilloma virus-associated endocervical adenocarcinomas.

Association of HPV16/18 genotype infection with the Silva pattern classification system in human papilloma virus-associated endocervical adenocarcinomas.

Educational Needs for Preventing and Managing Human Papillomavirus-Related Diseases in Men Living with HIV in Mexico.

Men living with HIV are at significantly higher risk of persistent high-risk human papillomavirus (hrHPV) infections and related diseases, including anal cancer. The optimal approach for anal cancer prevention remains unclear. In addition, limited knowledge and training among healthcare providers further hinder the implementation of effective screening and management strategies. To describe hrHPV prevalence and cytological abnormalities in men living with HIV and identify educational gaps in provider knowledge, this cross-sectional study recruited 178 men living with HIV (aged 18-60 years) from an HIV care clinic in Morelos, Mexico. Participants provided anal canal samples for hrHPV DNA testing and cytological evaluation. Descriptive statistics were used to report prevalence rates for hrHPV genotypes and cytological abnormalities. hrHPV prevalence was 80.9%. LSIL was most common (39.87%), with HSIL detected in 3.27%. The high prevalence of hrHPV and associated cytological abnormalities in men living with HIV underscores the need for educational programs to enhance provider knowledge and skills in HPV vaccination, screening, and management. Targeted training for physicians and other HIV care providers can address gaps in prevention and care, ultimately reducing the burden of HPV-related diseases in this high-risk population. The study may have implications for similar special populations with high HIV and HPV infection rates.

Unlocking the Interactions Between the Whole-Body Microbiome and HPV Infection: A Literature Review.

The human microbiome plays a vital role in maintaining human homeostasis, acting as a key regulator of host immunity and defense mechanisms. However, dysbiotic microbial communities may cause disruption of the symbiotic relationship between the host and the local microbiota, leading to the pathogenesis of various diseases, including viral infections and cancers. One of the most common infectious agents causing cancer is the human papilloma virus (HPV), which accounts for more than 90% of cervical cancers. In most cases, the host immune system is activated and clears HPV, whereas in some cases, the infection persists and can lead to precancerous lesions. Over the last two decades, the advent of next-generation sequencing (NGS) technology and bioinformatics has allowed a thorough and in-depth analysis of the microbial composition in various anatomical niches, allowing researchers to unveil the interactions and the underlying mechanisms through which the human microbiota could affect HPV infection establishment, persistence, and progression. Accordingly, the present narrative review aims to shed light on our understanding of the role of the human microbiome in the context of HPV infection and its progression, mainly to cervical cancer. Furthermore, we explore the mechanisms by which the composition and balance of microbial communities exert potential pathogenic or protective effects, leading to either HPV persistence and disease outcomes or clearance. Special interest is given to how the microbiome can modulate host immunity to HPV infection. Lastly, we summarize the latest findings on the therapeutic efficacy of probiotics and prebiotics in preventing and/or treating HPV infections and the potential of vaginal microbiota transplantation while highlighting the significance of personalized medicine approaches emerging from NGS-based microbiome profiling and artificial intelligence (AI) for the optimal management of HPV-related diseases.

The Role of CK7 and CK19 immunohistochemistry in the Evaluation of HPV-induced Cervical Squamous Precursor Epithelial Lesions.

Cervical cancer is the fourth common cancer in women worldwide. In most cases, the disease is induced by persistent high risk Human Papilloma Virus (HPV) infection. This study aimed to assess the role of CK7 and CK19 in human papillomavirus (HPV) induced cervical epithelial lesions using tissue microarray (TMA). A retrospective cohort study included females with cervical low-grade and high-grade intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL), and squamous cell carcinoma (SCC). TMA was constructed using specimens of 270 cases and 233 control tissues. CK7 and CK19 immunohistochemistry was scored as negative or positive. Follow-up information was gathered. CK7 was negative in about 85% of LSILs and positive in 55% of HSILs (p<0.001). CK19 showed positivity in about 50% of LSILs and 77% of the HSILs (p<0.001). For cases with available follow-up data, about 69% of CK7 positive LSILs progressed to higher grade lesions and 64% of CK7 positive HSILs showed progression to higher grades (CIN2 to CIN3) or to SCC. Regarding CK19, nearly 66% positive LSILs progressed to HSIL whereas, 62% of positive HSILs showed progression. LSILs with positivity for both markers progressed to HSIL in 70% of cases. CK7 and Ck19 positivity is significantly associated with higher-grade HPV-induced cervical lesions. Lesions with combined CK7 and CK19 positivity have a higher risk of progression to higher grade lesions.

Characterization of human papillomavirus genotypes infections in patients with cervical lesions and cervical cancer in Urumqi, Xinjiang from 2016 to 2023

BackgroundThe persistence of high-risk human papillomavirus (HPV) infection is well-established as a key etiological factor in the progression to cervical intraepithelial neoplasia (CIN) and cervical cancer (CC). This study aims to investigate the clinical and epidemiological characteristics associated with HR-HPV infections diagnosed in conjunction with cervical intraepithelial lesions in Urumqi, Xinjiang.MethodsBetween 2016 and 2023, we collected clinical data from 4,389 patients with cervical lesions who underwent colposcopic histopathological examination at the People’s Hospital of Xinjiang Uygur Autonomous Region. Cervical samples were obtained for HPV DNA genotyping and cytological analysis. Patients presenting with cervical abnormalities or abnormal cytology results subsequently underwent cervical biopsy.ResultsThe prevalence of HPV infection among 4,389 patients with cervical lesions were found to be 98.95% (4,345/4,389). Specifically, the prevalence of HPV types 16 and 18 were 78.87% (1,314/1,666). The five most common genotypes identified were HPV types 16, 52, 58, 31, and 33, with infection rates of 34.57%, 19.54%, 12.45%, 8.98%, and 7.66%, respectively. Among the patients with cervical lesions, cervical inflammation was observed in 522 individuals (11.90%), while the distribution of cervical intraepithelial neoplasia (CIN) was as follows: CIN I in 644 patients (14.67%), CIN II in 1,067 patients (24.31%), CIN III in 1,041 patients (23.72%), and CC in 1,115 patients (25.40%). The distribution of patients in the CC group was most prevalent among those aged ≥ 60 years (47.99%, 322/671). A high prevalence was also observed in the 30~39 year age group within the CIN III group (29.47%, 275/933). Han and Uygur patients accounted for 85.90% of cervical lesion cases (3,770/4,389). Hui patients were predominantly identified within the CIN II group (34.12%), whereas Uighur patients were most frequently observed in CC group (36.60%) (P < 0.005).ConclusionsPatients with cervical lesions had high HPV prevalence in Urumqi, Xinjiang. The five most prevalent HPV types identified in this population are HPV 16, 52, 58, 31, and 33. Epidemiological studies focusing on high-risk HPV types hold significant clinical implications, particularly in informing and guiding HPV vaccination strategies.

Efficacy of human papillomavirus vaccines in the prevention of male genital diseases: a systematic review.

To evaluate the results of randomised controlled trials (RCTs) regarding the efficacy of human papillomavirus (HPV) vaccination in preventing male genital-related diseases. A systematic search of English language literature using PubMed, Scopus, and Cochrane Library was performed in April 2024 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Evidence from four RCTs (including 7008 male participants) support the efficacy of the quadrivalent HPV vaccine in preventing genital warts and persistent HPV infection in HPV-naïve men. The low incidence of male genital malignancies in the control groups of the reported studies lead to underpowered evidence. However, vaccination leads to durable protection with a long-term follow-up of 10 years showing efficacy of 91.8% to prevent HPV 6-, 11-, 16-, or 18-related external genital lesions (EGLs) in HPV-naïve subjects. Additionally, the quadrivalent vaccine seems to effectively reduce the detection of DNA from all four HPV types. In summary, early quadrivalent HPV vaccination demonstrates efficacy in preventing HPV infection and EGLs in males. Well controlled prospective studies are needed to confirm the long-term efficacy, specifically in cancer prevention, in all men and specific subject subgroups, and to identify the targeted population who is most likely to benefit from early vaccination.

Persistence and clearance rates of human papillomaviruses in a cohort of women treated or not treated for cervical dysplasia in northwest Ethiopia

Persistence of high-risk Human papillomaviruses (HR-HPV) infection increases the risk of precancerous lesions development. The aim of this study was to assess the persistence and clearance rate of HPV infection. A prospective cohort study was conducted between January and December 2023 among patients attending gynecology unit of FHCSH in Bahir Dar, northwest Ethiopia. Out of 297 study participants, 95 women with HPV infected and cytological abnormalities were followed; of these 93.7% were HPV positive at the baseline study. Of which, 46.1% did not receive treatment, the rest 53.9% were treated. Among the women without treatment, HPV persistence and clearance rates were 65.9% and 34.1% respectively while persistence rate of 46.3% and clearance rate of 53.7% were observed in 12-month follow up period. Among women who received treatment, HPV persistence rate of 45.8% and clearance rate of 54.2% were recorded in six while persistence rate of 33.3% and clearance rate of 66.7% were observed in 12- month follow up period. The findings of our study indicated that the high persistence rate and low clearance rate of HPV infection. Detection of persistent HPV infection without treatment or after treatment should be considered as the main risk factor for the development or recurrence of cervical neoplasia.

Neutrophil/Lymphocyte Ratio (NLR) as a Predictive Marker for p16 Positivity and Cervical Cancer Progression: Insights from the SCOPE Study.

Background: Cervical cancer, primarily driven by persistent high-risk human papillomavirus (HPV) infections, remains a significant global health challenge. Systemic inflammatory markers, such as neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR), may reflect disease progression. This study examines the association between these markers and p16 positivity in cervical intraepithelial neoplasia (CIN) cases. Methods: This retrospective analysis included 395 patients undergoing LEEP conization. Data on HPV status, p16 immunostaining, and hematological parameters were collected. Statistical analyses, including Mann-Whitney U and chi-square tests, assessed relationships between markers and outcomes, with significance set at p < 0.05. Results: Elevated NLR was significantly associated with p16 positivity (p = 0.011) and HPV DNA positivity (p = 0.04). HPV-positive individuals showed higher mean NLR (2.15) compared to HPV-negative individuals (1.61). Receiver operating characteristic (ROC) analysis demonstrated moderate diagnostic accuracy for NLR (AUC = 0.610), highlighting its potential as a biomarker. No significant associations were observed for PLR or LMR with p16 positivity. These findings suggest systemic inflammation, indicated by NLR, contributes to HPV persistence and CIN progression. Conclusions: NLR is a valuable prognostic biomarker for HPV-related cervical disease, correlating with both p16 and HPV DNA positivity. Incorporating hematological and immunohistochemical markers may enhance personalized cervical cancer management.

Interconnectedness threat: unveiling the mechanisms behind human papillomavirus-induced cervical cancer

Cervical cancer is the fourth leading cause of cancer-related deaths among women worldwide, causing over 660,000 new cases and 350,000 deaths in 2022, with a disproportionately high burden in low-resource countries where access to treatment is limited. Human papillomavirus (HPV) is a common sexually transmitted infection that accounts for approximately 95% of cervical cancer cases. Persistent HPV infection can progress to cervical dysplasia, categorized into varying severities (CIN1, CIN2, and CIN3), which significantly increases cancer risk. The mechanism of HPV-induced malignancy involves the disruption of cellular apoptosis by integrating viral genetic material into cervical cells, particularly within the transformation zone. The viral proteins E6 and E7 play pivotal roles in cervical carcinogenesis by inhibiting tumor suppressor proteins, promoting uncontrolled cell proliferation, and evading immune responses, ultimately driving progression toward malignancy. Timely detection and intervention are essential for managing HPV-related cervical cancers. Preventative measures such as HPV vaccination have demonstrated substantial efficacy. Six vaccines targeting high-risk (HR) HPV strains are recommended before sexual activity or exposure. Despite these advancements, barriers, such as misinformation, logistical challenges, and limited healthcare infrastructure, persist, particularly in underserved regions. Advances in diagnostic and therapeutic technologies have offered new avenues for addressing these challenges. Next-generation sequencing and CRISPR gene editing are emerging as promising tools for HPV-related cancer treatment that enable precise and targeted interventions. Furthermore, artificial intelligence (AI) and imaging innovations have significantly enhanced diagnostic accuracy and personalized care. Pap smears and HPV DNA testing are indispensable tools for early detection. To tackle HPV-related cervical cancer globally, a multifaceted approach is required. Public health education, vaccination programs, research, and international collaboration are crucial. Public health campaigns should combat misinformation, strengthen vaccination programs, and focus on novel therapies, screening technologies, and next-generation sequencing.

Comparative analysis of SD biosensor standard™ M10 HPV and seegene anyplex™ II HPV HR for detecting high-risk human papillomavirus: a concordance study

BackgroundCervical cancer, primarily caused by persistent high-risk human papillomavirus (hrHPV) infections, is a significant health burden, particularly in low-resource settings such as Sarawak, Malaysia. Effective prevention depends on effective vaccination and early hrHPV detection. This study compares the performance of the point-of-care test (POCT) SD Biosensor Standard™ M10 HPV and laboratory-based Seegene Anyplex™ II HPV HR assay, focusing on their ability to detect and genotype hrHPV in self-collected high vaginal swab samples.MethodsA total of 151 archived self-sampled high vaginal swabs from the Sarawak Urban and Rural Action for Cervical Cancer Elimination Programme (Program SUARA) were analyzed. hrHPV detection and genotyping were performed using Anyplex, which identifies 14 hrHPV genotypes, and M10, which detects HPV16, HPV18, and other hrHPV categorized into six genogroups. Agreement between the assays was evaluated using Cohen’s Kappa (κ), McNemar’s test, and overall agreement percentages. Statistical significance was determined with p-values, and discordant results were further analyzed for potential diagnostic implications.ResultsThe overall agreement between M10 and Anyplex for hrHPV detection was 92.05% (κ = 0.84, 95% CI 0.75–0.93), indicating almost perfect agreement. M10 demonstrated comparable sensitivity for detecting HPV16, HPV18, and other hrHPV genotypes, achieving 96.91% agreement (κ = 0.89, 95%CI 0.73-1.00) in hrHPV classification when discordant results were excluded. Genogrouping also showed almost perfect agreement (κ = 0.91, 95% CI 0.82–0.98). McNemar’s test indicated no significant difference in hrHPV detection rates (p > 0.05), affirming their comparable performance in detecting clinically significant hrHPV infections.ConclusionThe SD Biosensor Standard™ M10 HPV POCT and the Seegene Anyplex™ II HPV HR assay demonstrated almost perfect agreement in hrHPV detection and classification, supporting their complementary roles in cervical cancer prevention. M10’s rapid, field-deployable design makes it suitable for resource-limited settings, while Anyplex provides enhanced genotyping capability in laboratory environments, allowing informed vaccine strategy. Incorporating both assays into cervical cancer prevention programs can improve screening coverage and accessibility, particularly in underserved areas. These findings align with the World Health Organization’s cervical cancer elimination goals, reinforcing the importance of adaptable diagnostic tools in diverse healthcare contexts.

Epidemiological, economic and humanistic burden of cervical intraepithelial neoplasia in Europe: A systematic literature review.

Epidemiological, economic and humanistic burden of cervical intraepithelial neoplasia in Europe: A systematic literature review.

Tissue microarray validation in cervical carcinoma studies. A methodological approach.

Tissue microarrays (TMAs) are a cost-effective tool to study biomarkers in clinical research. Cervical cancer (CC) is one of the most prevalent in women worldwide, with the highest prevalence in low-middle-income countries due to a lack of organized screening. CC is associated with persistent high-risk human papillomavirus infection. Several biomarkers have been studied for diagnostic, therapeutic, and prognostic purposes. We aimed to evaluate and validate the effectiveness of TMA in CC compared to whole slide images (WSs). We selected and anonymized twenty cases of CC. P16, cytokeratin 5 (CK5), cytokeratin 7 (CK7), programmed death-ligand 1 (PD-L1), and CD8 expression were immunohistochemically investigated. All WS were scanned and 10 representative virtual TMA cores with 0.6 mm diameter per sample were selected. Ten random combinations of 1-5 cylinders per case were assessed for each biomarker. The agreement of scoring between TMA and WS was evaluated by kappa statistics. We found that three cores of 0.6 mm on TMA can accurately represent WS in our setting. The Kappa value between TMA and WS varied from 1 for p16 to 0.61 for PD-L1. Our study presents an approach to address TMA sampling that could be generalized to TMA-based research, regardless of the tissue and biomarkers of interest.

Human Papillomavirus Infections and Sequela in Women.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States, with up to 90% of females infected at some point in their lifetime. While most HPV infections will be cleared by the immune system within 2 years, persistent HPV infection may result in anogenital warts, dysplasia of the cervix, vagina, vulva, and squamous cell carcinoma. This chapter will review the epidemiology, microbiology, progression, and treatment of HPV-related genital disease in women.

The role of HPV in the pathology of the lower genital tract in women with infertility

Human papillomavirus (HPV) is the most common sexually transmitted infection. An increasing number of scientific works are devoted to studying the role of HPV in reproductive disorders in infertile couples. This virus is one of the most common sexual infections among men and women. Although most studies have focused on the oncogenic properties of HPV, the impact of the virus on fertility and reproductive capacity remains poorly understood.The objective: to assess the clinical significance of the impact of HPV infection in women with infertility based on clinical and laboratory indicators of HPV viral load and the state of the vaginal microbiome.Materials and methods. A survey of 184 women of reproductive age (20–40 years, mean age – 31–35 years) with infertility was conducted. 58 persons of them were diagnosed with infertility, chronic inflammatory processes of the female genital organs and positive HPV status (main group). The comparison group included 50 healthy women of reproductive age without HPV infection.Polymerase chain reaction (PCR) was used to detect HPV, as well as bacterioscopic, bacteriological methods and PCR to determine microbiological status. The results were analyzed using parametric and nonparametric statistical methods.Results. HPV was found in 31.5% of women with infertility, of which 60.3% had high-risk oncogenic strains – the most common were HPV-16, HPV-31 and HPV-53. HPV persistence was determined in 63.8% of cases. Secondary infertility was diagnosed in 74.1% of women in the main group, while primary infertility was diagnosed in 25.9%. A relationship was established between the presence of HPV and an increased risk of pregnancy complications, such as spontaneous abortions (20.7%) and recurrent miscarriage (8.6%).Gynecological examinations revealed a high level of chronic inflammatory processes of the genital organs in patients in the main group: vulvovaginitis (51.7%), inflammation of the appendages (31%), uterus (17.2%), as well as cervical pathologies, including background diseases (22.4%) and precancerous conditions (75.8%). HPV infection was often combined with other infections, such as Chlamydia trachomatis (8.6%), Ureaplasma urealyticum (24.1%), Mycoplasma hominis (27.6%).Imbalance of the vaginal microbiome, manifested by a decreased number of Lactobacillus (87.9%) and an increased amount of opportunistic microflora (Staphylococcus spp., Enterococcus faecalis, Gardnerella vaginalis), correlated with HPV persistence. Women with HPV and bacterial vaginosis had the highest degree of microbiome imbalance.Conclusions. HPV infection and its persistence significantly affect the course of chronic inflammatory diseases of the female genital organs and the reproductive function of women. HPV infection is associated with an increased risk cervical dysplasia, inflammatory diseases and obstetric complications. It is important to introduce HPV vaccination to prevent infection, as well as correct the microbiome imbalance as a component of complex treatment.