Persistent Human Papillomavirus Research Articles

Immunogenicity and safety of the fourth dose of quadrivalent human papillomavirus (HPV) vaccine in immunosuppressed women who did not seroconvert after three doses

IntroductionImmunocompromised persons have high risk of persistent human papillomavirus (HPV) infection and HPV-related diseases, and lower immune response to vaccines. This study evaluated the immunogenicity and safety of administering a fourth dose of quadrivalent (4v)HPV vaccine in immunosuppressed women who did not seroconvert after three doses.MethodsAn open-label, not-controlled trial included immunosuppressed women (solid organ transplant patients and women receiving treatment for SLE) who did not seroconvert to at least one of the four HPV vaccine types after three 4vHPV vaccine doses. All participants received a fourth 4vHPV vaccine dose (median 27 months after third dose). Immunogenicity was evaluated a month after the fourth dose, by measuring seroconversion rates and antibody geometric mean concentration (GMC).ResultsTwenty-three women were included. Among women who did not seroconvert for each vaccine type after three doses, 2/10 seroconverted to HPV6, 3/10 to HPV11, 3/10 to HPV16 and 6/18 to HPV18, after the fourth 4vHPV dose. There was an increase in antibody GMC for HPV 6, 16, 18, with highest increase for HPV16 (from 6.02 to 44.63 International Units). There was no increase of anti-HPV-11. Within seven days after vaccination, only three of the 23 vaccinees reported any adverse event, none of which were classified as serious.ConclusionsAlthough safe, the fourth 4vHPV vaccine dose led to seroconversion in only few immunosuppressed women who had not seroconverted after three doses.

Mapping the HPV Landscape in South African Women: A Systematic Review and Meta-Analysis of Viral Genotypes, Microbiota, and Immune Signals

This systematic review and meta-analysis evaluate human papillomavirus (HPV) prevalence, genotype distribution, and associations with cervicovaginal microbiota and cytokine profiles among South African women, where cervical cancer ranks as the second most common cancer. PubMed, SCOPUS, and Web of Science were searched for studies on HPV infection up to 21 September 2024. The pooled prevalence was estimated using a random-effects model, with subgroup analyses by province, sample type, and HIV status. Publication bias was evaluated using funnel plots and Egger’s test. Of the 19,765 studies screened, 120 met the inclusion criteria, comprising 83,266 participants. Results indicate a high HPV burden, with a pooled prevalence of 58% (95% CI: 52–64%), varying regionally from 53% (95% CI: 41–65%) to 64% (95% CI: 55–73%), with some regions under-researched. Cervical samples had the highest HPV prevalence (60% (95% CI: 54–66%)), while non-genital samples were less studied. High-risk (HR) HPV types, notably HPV 16 (7.5%), HPV 35 (4.1%), and HPV 18 (3.9%), were prominent, with HPV 35 emphasizing the need for expanded vaccine coverage. HIV-positive women had a higher pooled HPV prevalence (63% (95% CI: 55–71%)). Funnel plot analysis and Egger’s test suggested a potential publication bias (p = 0.047). HPV-positive women exhibited lower Lactobacillus levels and an increase in Bacterial Vaginosis (BV)-associated species like Gardnerella, potentially supporting HPV persistence. Cytokine analysis showed elevated MIP-1α and MIP-1β in HPV infections, though cytokine profiles may depend on HPV genotypes. These findings underscore the need for research on HPV–microbiome-immune interactions and call for comprehensive HPV-prevention strategies, including vaccines targeting regional HPV types and tailored interventions for HIV-positive populations.

Genome-Wide Association Study of Persistent Anal Human Papillomavirus Infection Among HIV-Positive Males in Taizhou, China: A Cohort Study.

The determinants of persistent human papillomavirus (HPV) infection remain largely unknown, and existing studies have predominantly focused on the female population. Individual genetic background may influence the persistence of HPV infection, we the evidence overall and among human immunodeficiency virus (HIV)-positive males are very limited. We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with anal HPV persistence, based on a cohort designed to study the natural history of anal HPV infection among HIV-positive males in Taizhou, China from 2016 to 2022. A total of 322 HIV-positive males with anal HPV infection, with a mean age of 43.0 (standard deviation [SD]: 13.8) years, were included in this GWAS. The median follow-up time was 1.8 (interquartile range [IQR]: 1.5-2.0) years. The persistence of any type of HPV infection was 53.4%. After adjusting for age and sexual orientation, there were 2 SNPs with p < 1 × 10-5 and 24 SNPs with p < 1 × 10-4. The most closely associated with HPV persistence in additive models were rs7359031 (LOC105370461, odds ratio [OR]T/C = 0.36, 95% confidence interval [CI]: 0.24-0.56; p = 6.67 × 10-6) located at 14q21.1, and rs11046048 (PYROXD1, ORC/A = 0.41, 95% CI: 0.28-0.60; p = 7.80 × 10-6) located at 12p12.1. Other SNPs were mainly located at 6q23.3 (HBS1L-MYB) and 6p21.33 (CCHCR1, PSORS1C3). LOC105370461, PYROXD1, HBS1L-MYB, CCHCR1, and PSORS1C3 may be susceptible genes for HPV persistence. We appeal further studies to validate these associations and examine the underlying mechanisms.

Human umbilical cord mesenchymal stem cells small extracellular vesicles-derived miR-370-3p inhibits cervical precancerous lesions by targeting DHCR24

Abstract Background Cervical cancer is often caused by persistent high-risk human papillomavirus (HPV) infection, causing precancerous lesions. Human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (hucMSC-sEV) exhibit diverse effects on tumors. This study investigates hucMSC-sEV, the impact and mechanisms on HPV-positive cervical precancerous lesion cells to provide new treatment insights. Materials and Methods We previously obtained hucMSC and hucMSC-sEV. In vitro experiments evaluated hucMSC-sEV effects on the proliferation and migration of S12 cells (derived from cervical precancerous lesions). Bioinformatics identified key microRNA components, and their impact on S12 cell proliferation and migration was investigated. The target gene of the microRNA component was predicted and confirmed via bioinformatics and dual-luciferase reporter assays. Lentiviral systems overexpressed target gene in S12 cells to examine the effects on microRNA impacts. SH-42 inhibitor was used to investigate target gene treatment potential. Immunohistochemistry assessed target gene expression in cervical precancerous lesions tissue. Results hucMSC-sEV significantly inhibited S12 cell proliferation and migration. Bioinformatics identified miR-370-3p as an effective cargo, which also suppressed S12 cell proliferation and migration. miR-370-3p was confirmed targeting DHCR24 (24-Dehydrocholesterol Reductase). DHCR24 overexpression reversed miR-370-3p’s inhibitory effects, while SH-42 counteracted DHCR24 overexpression’s promoting effects. Clinical specimen analysis supported these findings, demonstrating a positive correlation between DHCR24 protein expression and cervical precancerous lesions’ progression. Conclusions hucMSC-sEV inhibits S12 cell proliferation and migration, mediated by miR-370-3p targeting DHCR24 to regulate cellular cholesterol content. DHCR24 inhibition reduces the cholesterol level and cell functions, suggesting its potential as a therapeutic target in cervical precancerous lesions.

Abstract PR003: Preventing and treating HPV-related Cancer with mRNA Therapy Expressing A DC-targeting Antigen

Abstract Persistent human papillomavirus (HPV) infection is linked to several malignancies, highlighting the need for effective therapeutic vaccines. In this study, we tested a lipid nanoparticle-encapsulated mRNA vaccine expressing tHA-mE7-mE6. By mutating the E6 and E7 proteins to reduce their tumorigenicity and fusing them with a truncated influenza hemagglutinin protein (tHA) for better antigen uptake, we improved the vaccine’s efficacy. The tHA-mE7-mE6 mRNA vaccine showed superior results compared to mE7-mE6 mRNA, achieving complete tumor regression and preventing new tumors in an E6 and E7 positive model. It elicited a strong CD8+ T-cell response, with antigen-specific CD8+ T-cells found in the spleen, blood, and tumors. Additionally, the therapy increased DC and NK cell infiltration into tumors. Overall, this study demonstrates that the tHA-mE7-mE6 mRNA vaccine induces a potent anti-tumor immune response, showing promise for treating HPV-induced cancers and preventing recurrence. Citation Format: William Jia. Preventing and treating HPV-related Cancer with mRNA Therapy Expressing A DC-targeting Antigen [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr PR003.

Quadrivalent HPV (4vHPV) vaccine immunogenicity and safety in women using immunosuppressive drugs due to solid organ transplant.

Immunocompromised persons are at high risk of persistent Human Papilloma Virus (HPV) infection and associated diseases. Few studies evaluated HPV vaccines in immunocompromised persons. This study aimed to evaluate the quadrivalent HPV vaccine (4vHPV) immunogenicity and safety in solid organ transplant (SOT) recipients, in comparison to immunocompetent women (IC). Open-label clinical trial that enrolled SOT recipients and immunocompetent women aged 18 to 45 years. All participants received three doses of 4vHPV vaccine. Blood samples were drawn for evaluation of immune responses at baseline and one month after the third vaccination. Seroconversion rates and antibody geometric mean concentration (GMC) against HPV 6, 11, 16, 18, 31, 35, 52 and 58 were measured with in-house multiplexed serology assay (xMAP technology). Follow-up for the local and systemic adverse events (AEs) continued for seven days after each vaccination. Severe AEs were evaluated throughout the study. 125 SOT and 132 immunocompetent women were enrolled; 105 (84%) SOT and 119 (90%) immunocompetent women completed the study. At baseline, HPV seropositivity was not significantly different between groups. Seroconversion rates were significantly lower in SOT (HPV18, 57%; HPV6 and 16, 69%; and HPV11, 72%) than in immunocompetent women (100% seroconversion to all vaccine types) (p<0.001). Antibody GMCs of all four HPV vaccine types were also significantly lower in SOT (p<0.001). Pain in the injection site and headache were the most frequent adverse event in both groups. Local pain was more frequent in immunocompetent women than in SOT recipients. Rates of other AEs were comparable in both groups. 4vHPV vaccine was well-tolerated by SOT recipients. We found strong evidence of lower humoral immune responses to 4vHPV vaccine in SOT compared to immunocompetent women, which strengthen recommendation of routine cervical cancer screening in SOT recipients regardless of HPV vaccination status.

A Narrative Review of the Putative Etiologic Role and Diagnostic Utility of the Cervicovaginal Microbiome in Human Papillomavirus-Associated Cervical Carcinogenesis.

The cervicovaginal microbiome (CVM) may contribute to human papillomavirus (HPV)-associated cervical carcinogenesis. We summarized the literature on the CVM in cervical carcinogenesis by searching Medline, Web of Science, and Embase for articles that sequenced the CVM using metagenomics. Additionally, we identified studies assessing the diagnostic role of the CVM in cervical carcinogenesis by searching PubMed. We performed an environmental scan of Google and Google Scholar to review common CVM characterization techniques. Twenty-eight records presented or summarized associations between the CVM and HPV acquisition, prevalence, persistence, clearance, and cervical lesions or cancer, while three studies identified bacterial taxa detecting high-risk HPV prevalence or cervical lesions. The area under the curve ranged from 0.802 to 0.952. 16S ribosomal RNA gene sequencing and whole metagenome sequencing have sufficient resolution to study the CVM bacteriome. Bacterial communities may have important implications in cervical cancer; however, there is a need for methodological standardization for CVM characterization.

Differential study on the relationship between HPV infection and vaginal microbiota composition in Uygur and Han women

ObjectiveTo analysis the differential composition in vaginal microbial communities following HPV infection in Uygur and Han women, and to Explore the correlation between these difference and the degree of Human Papillomavirus (HPV) infection in Uygur women compared to Han women. MethodsA total of 151 Uygur and Han women, with and without HPV, were studied at Xinjiang Uygur Autonomous Region People's Hospital (June 2021–June 2022). These participants were divided into six groups: Uygur control (CV), Uygur transient infection (TPV), Uygur persistent infection (PPV), Han control (CH), Han transient infection (TPH), Han persistent infection (PPH). Vaginal microbiota diversity and dominant bacteria with or without HPV infection were compared using 16S rDNA sequencing. ResultsAfter HPV infection, vaginal pH increased significantly in Uygur and Han women. Vaginal environment cleanliness decreased notably only in Han women (P < 0.05). In Han women, Lactobacillus and Gardnerella dominated both with or without HPV infection. Prevotella, Streptococcus, and Atopobium decreased, while Sneathia increased significantly in persistent HPV cases. Among Uygur women, Gardnerella, Streptococcus, Prevotella, and Shuttleworthia increased significantly in the TPV group, with lower Lactobacillus compared to CV and PPV groups. Bacterial diversity indices (Chao1, Shannon, Simpson) were significantly lower in TPH compared to CH (P < 0.05), with no significant difference in PPH compared to CH (P > 0.05). Chao1 index was significantly lower in TPH than TPV (P < 0.05), with no difference between PPH and PPV (P > 0.05). CV group's Chao1 index was significantly lower than CH (P < 0.01). PCoA and NMDS analyses showed distinct vaginal microbiota between TPH and TPV groups. LEfSe identified 20 differentially expressed taxa in CH-TPH-PPH comparison and 17 in CV-TPV-PPV. ConclusionOur study reveals ethnic-specific differences in vaginal microbial responses to HPV infection, with notable alterations in diversity and composition. The differential patterns observed between Uygur and Han women underscore the importance of considering host ethnicity in HPV-related microbial dysbiosis, emphasizing the need for tailored interventions targeting microbial signatures to enhance HPV prevention and management strategies.

A prospective cohort study comparing efficacy of 1 dose of quadrivalent human papillomavirus vaccine to 2 and 3 doses at an average follow up of 12 years postvaccination.

While recommending a human papillomavirus (HPV) single-dose vaccination schedule in 2022, the World Health Organization highlighted the need for long-term follow-up studies to monitor waning of protection. We report on vaccine efficacy against HPV infections in 1-, 2-, and 3-dose schedules and protection against cervical precancers at a median follow-up of 12 years postvaccination. This randomized multicenter study in India was originally designed to vaccinate unmarried girls aged 10-18 years with either 2 or 3 doses of quadrivalent HPV vaccine. A ministerial decree to halt vaccination in trials resulted in the creation of cohorts receiving different doses, including just a single dose. Cohorts were assessed for incident and persistent infections by genotyping cervical samples collected yearly for 4 consecutive years after participants were married. Cervical screening with an HPV test was initiated at age 25 years for married participants. Age- and site-matched unvaccinated married women were recruited to be compared with vaccinated cohorts. Vaccine efficacy was assessed using proportional incidence ratios. The number of participants in the 1-, 2- (at 0 and 6 months), and 3-dose cohorts was 4949, 4980, and 4348, respectively. Of the recipients, 71%-82% in the different cohorts were eligible to provide samples for genotyping. Vaccine efficacy against persistent HPV 16 and 18 infection was 92.0% (95% confidence interval [CI] = 87.0% to 95.0%) in 3022 recipients of the single dose; and comparable with that observed in the 2-dose arm (94.8%, 95% CI = 90.0% to 97.3%) and the 3-dose arm (95.3%, 95% CI = 90.9% to 97.5%). No high-grade precancer associated with HPV 16 and 18 was detected among vaccinated participants compared with 8 precancers detected among the unvaccinated women. This observational cohort study has established that a single dose of HPV vaccine provides high protective efficacy against persistent HPV 16 and 18 infections and associated neoplasia 15 years postvaccination.

Long-Term Infection With a Particular Human Papillomavirus (HPV) Genotype, HPV Subtype, or HPV Genomic Variant Does not Significantly Influence the Clinical Course of Recurrent Respiratory Papillomatosis.

Recurrent respiratory papillomatosis (RRP) is caused by human papillomaviruses (HPV) 6 and 11, but the role of their genomic variants in the disease's clinical course is unclear. This study investigated whether long-term persistence of a particular HPV genotype, subtype or genomic variant influences the RRP clinical course. HPV genotyping was performed in paired baseline and follow-up RRP laryngeal tissue specimens of 59 patients. HPV6 and HPV11 genomic variants were determined in paired tissue specimens taken at least 10 years apart in 20 selected patients. HPV was identified in 58/59 patients, most commonly HPV6 (40/58), followed by HPV11 (17/58). The most prevalent HPV genomic variant was HPV11 A2. HPV6 A and HPV6 B1 were most frequent in aggressive RRP. In all patients, identical HPV genomic variants were identified in both paired specimens. RRP results from a long-term infection with the same HPV genomic variant that can be identified decades after disease onset. We report the longest duration of genetically confirmed persistent HPV infection in peer-reviewed literature, during a 44-year interval in a patient with HPB6 B1. This study suggests that infection with a particular HPV genotype, subtype, or genomic variant does not significantly influence the clinical course of RRP.

Prospectives of developing therapeutic HPV vaccines

Human papillomavirus (HPV) represents one of the most serious global public health problems. Malignant female and male diseases mainly result from persistent HPV infection. Cancer belongs to a high mortality rate disease. It has been established that HPV infection causes about 70% vaginal cancer, 50% male genital cancer, 90% anal cancer and 60% head-and-neck cancer. Annually, a large number of people develop various HPV-caused cancer types, dominated by cervical cancer, one of the most common and aggressive types of cancer that threatens health holding the fourth place among most female common cancer worldwide. According to the World Health Organization (WHO), in 2020, about 600 cases of cervical cancer are recorded daily in different countries. Emergence of cervical cancer is closely related to factors such as long-term (persistent) HPV infection and somatic mutations of the host genome. Although HPV infection can be detected and cured early with highly effective screening methods and surgical procedures, the carcinogenic risk of HPV related diseases constantly increases, which elimination faces certain difficulties, especially in low- and mid-developed countries. The most acceptable solution to this is development and implementation of therapeutic vaccines for prevention and treatment of HPV related diseases. Three licensed HPV vaccines based on L1 type virus-like particles (L1-VLPs) technology are available globally: bivalent (HPV-2), quadrivalent (HPV-4) and nonavalent (HPV-9) vaccines. These vaccines demonstrated effectiveness in reducing HPV-related cervical cancer rate by up to 90% worldwide. However, the therapeutic effect of these vaccines on persistent HPV infection and lesions has not been observed. Therapeutic HPV vaccines candidates targeted Ye6/Ye7 cancer proteins activate cellular immunity that eliminates existing HPV infection. Here we review types, mechanisms of action and clinical effects of therapeutic HPV vaccines, as well as current and future developments in the field for prevention and treatment of HPV related diseases.

HPV Vaccines

Human papillomavirus (HPV) is a double-stranded DNA virus and a source of infection that primarily affects the skin and mucous membranes. It can be transmitted through sexual contact and contaminated surfaces. There are over 200 genotypes of HPV, approximately 40 of which infect the anogenital region. High-risk HPV types, such as HPV-16 and HPV-18, can lead to the development of various cancers, particularly cervical cancer. Factors that increase the risk of transmission include having multiple sexual partners, early initiation of sexual activity, and having an uncircumcised male partner. Low socioeconomic status, poor nutrition, immunosuppression, and co-infections with HIV, genital herpes, or chlamydia can result in persistent and severe HPV infection. Three types of vaccines have been developed against HPV: bivalent, quadrivalent, and nonavalent vaccines. The bivalent vaccine provides protection against HPV-16 and HPV-18; the quadrivalent vaccine is effective against HPV-16, HPV-18, as well as HPV-6 and HPV-11. The nonavalent vaccine offers the broadest protection, covering nine different types of HPV. All vaccines are approved for males and females aged 9 and older. Vaccination before the onset of sexual activity significantly increases protection against cervical cancer.

Design and antiviral assessment of a panel of fusion proteins targeting human papillomavirus type 16.

Cervical cancer ranks as the third most prevalent malignancy in women worldwide. The persistence of Human papillomavirus (HPV) infection stands out as the foremost risk factor for cervical cancer development. Among the numerous HPV subtypes, HPV16 infection emerges as the primary pathogenic determinant of cervical cancer. To date, no specific drugs have been approved. In this study, we engineered two high-affinity fusion protein targeting HPV16 L1 protein based on the alpaca-derived single-domain antibody 2C12 previously obtained in our laboratory. These two fusion proteins exhibited potent neutralizing activity against HPV16 pseudovirus with IC50 values of 7.8 nM and 6.5 nM, respectively. Molecular docking analysis revealed that 2C12 formed ten pairs of hydrogen bonds with HPV16 L1, among which Arg39 and Thr100 established multiple pairs of hydrogen bonds with HPV16 L1, indicating their crucial roles in antigen-antibody binding process. These structural and biological findings underscore the effective binding capacity of these fusion proteins to HPV16, leading to reduced viral load and providing valuable insights into therapeutic antibody and vaccine development against HPV 16 infection.

Germline variants of homology-directed repair or mismatch repair genes in cervical cancer.

While cervical cancer is associated with a persistent human papillomavirus (HPV) infection, the progression to cancer is influenced by genomic risk factors that have remained largely obscure. Pathogenic variants in genes of the homology-directed repair (HDR) or mismatch repair (MMR) are known to predispose to diverse tumour entities including breast and ovarian cancer (HDR) or colon and endometrial cancer (MMR). We here investigate the spectrum of HDR and MMR germline variants in cervical cancer, with particular focus on the HPV status and histological subgroups. We performed targeted next-generation sequencing for 5 MMR genes and 12 HDR genes on 728 German patients with cervical dysplasia or invasive cancer. In total, 4% of our patients carried a pathogenic germline variant, based on ClinVar classifications and additional ESM1b and AlphaMissense predictions. These included 15 patients with truncating variants in HDR genes (BARD1, BRCA1, BRCA2, BRIP1, FANCM, RAD51D and SLX4). MMR-related gene variants were less prevalent and mainly of the missense type. While MMR-related gene variants tended to associate with adenocarcinomas, HDR gene variants were commonly observed in squamous cancers. While one patient with HPV-negative cancer carried a pathogenic MMR gene variant (in MSH6), the HDR germline variants were found in patients with HPV-positive cancers and tended to associate with HPV18. Taken together, our study supports a potentially risk-modifying role of MMR and HDR germline variants in cervical cancer but no association with HPV-negative status. These variants may be exploitable in future therapeutic managements.

An integrated approach to secondary prevention of cervical intraepithelial neoplasia

Secondary prevention of cervical precancer is aimed at preventing recurrence of cervical intraepithelial neoplasia (CIN) after excisional treatment. Recurrence of CIN after surgical treatment occurs in 8.1–14.4% of cases, which increases the risk of developing cervical cancer (CC). Despite the high effectiveness of local surgical treatment of patients with high-grade intraepithelial lesions (HSIL), an increased risk of late diagnosis of cervical cancer has been proven in comparison with the risk in the general population. The review article presents current data on factors that increase the potential risk of recurrence of precancer. Human papillomavirus (HPV) persistence is considered one of the leading predictors of relapse of CIN2+, regardless of the type of excision treatment. The combination of persistent high-risk (HR) HPV and a positive sectional margin significantly increases the risk of persistent/recurrent CIN2+. A negative co-test after conization during follow-up contributes to a favorable prognosis and the development of HSIL is observed less frequently than in the population. Only an integrated approach, including detection of cervical HPV HR infection after excisional treatment of CIN, assessment of the radicality of resection and timely measures to eliminate ineffective treatment, as well as subsequent active monitoring of patients, allows avoiding its recurrence and progression of cervical precancer

HPV Infection and Prevention in Patients With Immune-Mediated Inflammatory Diseases: A Scoping Review.

Human papillomavirus (HPV) infections are a significant public health concern as they cause various cancers, including those of the cervix, vulva, vagina, anus, penis, and oropharynx, in both women and men. Individuals with immune-mediated inflammatory diseases, particularly systemic lupus erythematosus, have an increased risk of developing persistent HPV infection and subsequent precancerous lesions due to their immunosuppression. Vaccination and screening for precancerous lesions are 2 central management strategies that must be implemented in patients with immune-mediated inflammatory diseases. Although HPV vaccination has been proven to be safe and effective in these patients, coverage remains low and should be encouraged. Screening for cervical cancer should be more widely implemented in this population, as recommended in guidelines for other immunosuppressed patients. Catch-up vaccination, vaginal self-sampling screening for HPV detection, and therapeutic vaccination are new options that should be considered.

Prevalence of 14 high-risk human papillomavirus subtypes among volunteers of cervical cancer screening by Papanicolaou smear cytology from a tertiary care institute of Assam, India

Abstract: BACKGROUND: In India, cervical cancer is the second most prevalent cancer among women, constituting 18.3% of all cases. Persistent high-risk human papillomavirus (HPV) infection is a well-established risk factor for cervical cancer. OBJECTIVES: This study aimed to assess the prevalence of 14 high-risk HPV subtypes and their association with abnormal cytology among women in Upper Assam. MATERIALS AND METHODS: This descriptive cross-sectional study was conducted from February 2022 to April 2023 at a tertiary care center in Assam. A total of 100 women aged 23-72 years underwent cervical sample collection for HPV DNA analysis via real-time polymerase chain reaction and cytological examination of Papanicolaou (PAP) smears. RESULTS: The overall HPV prevalence was 13%, with 10% testing positive for HPV 16/18 and 6% for other high-risk subtypes. Coinfection with HPV 16/18 and other subtypes was found in 3% of cases. The mean age of HPV-positive participants was 46 years. Cytology results showed 87% normal, 11% inflammatory changes, and 2% epithelial cell abnormalities. The Chi-square analysis (α = 0.05) showed no significant association between age (P = 0.24), religion (P = 0.49), or education (P = 0.57) and HPV positivity, but the study showed a significant association of HPV infection with menstrual cycle (P = 0.04). The study also showed a significant association between cervical cytology and HPV positivity (P = 0.0087). DISCUSSION: The present study’s findings on the prevalence of all 14 high-risk HPV subtypes contribute new insights to the existing literature, although the slightly lower prevalence may be attributed to the sample size and demographic factors. The findings emphasize the need for regular screening by PAP smear as well as by HPV DNA detection, as cytological abnormalities were detected even in those without HPV infection. CONCLUSION: Along with 16/18 HPV subtypes, a longitudinal study may offer important insights into the development of coinfections and the other 12 subtypes of HPV infection, as well as the spectrum of dysplasia and in situ cervical cancer.

Entangled Connections: HIV and HPV Interplay in Cervical Cancer-A Comprehensive Review.

Cervical cancer (CC) remains a prevalent malignancy and a significant global public health concern, primarily driven by persistent human papillomavirus (HPV) infections. The infectious nature of HPV underscores the preventability of CC through vaccination and screening programs. In addition to HPV, factors such as age, parity, smoking, hormonal contraceptives, and HIV co-infection elevate the risk of CC. HIV-associated immunodeficiency exacerbates susceptibility to infections and cancers, making CC a defining condition for acquired immune deficiency syndrome (AIDS) and one of the most commonly diagnosed cancers among women living with HIV (WLWH). These women face higher risks of HPV exposure due to sexual behavior and often encounter economic, social, and psychological barriers to screening. HIV and HPV co-infection can potentially accelerate CC carcinogenesis, with WLWH typically being diagnosed with CC earlier than their HIV-negative counterparts. Antiretroviral therapy (ART), which reduces AIDS-related mortality, also lowers the risk of invasive CC. The interaction between HIV and HPV is intricate and bidirectional. This summary reviews current evidence on HPV infection and CC in WLWH, highlighting the connections across pathogenesis, prevention, diagnosis, and treatment.

Fibroblasts Regulate the Transformation Potential of Human Papillomavirus-positive Keratinocytes.

Persistent human papillomavirus (HPV) infection is necessary but insufficient for viral oncogenesis. Additional contributing co-factors, such as immune evasion and viral integration have been implicated in HPV-induced cancer progression. It is widely accepted that HPV+ keratinocytes require co-culture with fibroblasts to maintain viral episome expression, yet the exact mechanisms for this have yet to be elucidated. Here we present comprehensive RNA sequencing and proteomic analysis demonstrating that fibroblasts not only support the viral life cycle, but reduce HPV+ keratinocyte transformation. Our co-culture models offer novel insights into HPV-related transformation mechanisms.

Global pattern of persistent human papillomavirus infection in female genital tract: An update system review and meta-analysis

We analyzed the type-specific persistent infection of high-risk human papillomavirus (HR-HPV) across different continents, aiming to offer valuable insights into the implementation and development of HPV vaccines. There were 129 studies included 656,555 participants. The weighted mean time for any persistent HPV infection was 13.29months. The single and multiple HPV infection were persistent for median of 12.27 and 18.99months, respectively. HPV35 is the common genotype of persistent infection in Asia and Africa, as well as HPV53 in Europe. Individuals (>50 years old) were to be more prone to persistent infection. Our study revealed approximately 50% of persistent HPV infection resolved after two years. A 24-month interval for HPV testing is proposed as a way to identify persistent HPV infection. In addition, to develop region-specific guidelines for HPV vaccines can be utilized as references for the diagnosis and treatment of cervical cancer.