Human Papillomavirus Type Research Articles

Cytological features of human papillomavirus-infected immature squamous metaplastic cells from cervical intraepithelial neoplasia grade 2.

In reflex cytology, the presence of prominent nucleoli in immature metaplastic squamous cells (IM) may be underdiagnosed due to variations in interpretation. The aim of this study is to identify human papillomaviruses (HPVs) that infect IM clusters in cervical intraepithelial neoplasia 2 (CIN2) on Papanicolaou (Pap) smears to determine the cytological features of lesion-derived cells. Thirty-two patients with a simultaneous diagnosis of CIN2 on biopsy and high-grade squamous intraepithelial lesions (HSIL) on cytology as well as with IM clusters on HSIL smears were included. CIN2 tissues and HSIL and IM clusters on Pap smears were isolated by manual microdissection, and HPV types were identified by PCR-based genotyping. The nuclear area within the IM clusters was also measured. The median nuclear area of HPV-negative IM clusters was 48 μm2 , with a coefficient of variation (CV) of 0.20; those of HPV-positive clusters were 66 μm2 and 0.34, respectively. The cut-off values of the nuclear area and CV for HPV positivity were 62 μm2 and 0.25, respectively. IM clusters composed of cells with a nuclear area of more than twice that of neutrophils or cells with a wide variation in nuclear sizes are likely to be neoplastic cells caused by HPV.

Prospective, multi-center post-marketing surveillance cohort study to monitor the safety of the human papillomavirus-16/18 AS04-adjuvanted vaccine in Chinese girls and women aged 9 to 45 years, 2018–2020

ABSTRACT Following the approval of Cervarix for the immunization of girls and women in China against high-risk human papillomavirus types 16 and 18, a non-interventional post-authorization safety study was performed. A multi-center prospective cohort study assessed safety following Cervarix vaccination of Chinese girls and women aged 9–45 years between 31 May 2018 and 3 December 2020. Adverse events following immunization (AEFIs), potential immune-mediated diseases (pIMDs), and pregnancy-related outcomes were collected up to 12 months from the third immunization or 24 months from the first immunization, whichever came first. Among 3,013 women who received 8,839 Cervarix doses, 167 (5.5%) reported ≥ 1 any AEFI, and 22 (0.7%) reported 40 serious AEFIs. During the 30 days after each dose, 147 women (4.9%) reported 211 medically attended AEFIs, including 3 serious AEFIs reported by 1 woman (0.03%). One woman reported a pIMD. Cervarix was inadvertently administered to 65 women (2.2%) within 60 days before conception or during pregnancy. Of these women, 34 (52.3%) gave birth to live infant(s) with no apparent congenital anomalies, and 1 (1.5%) woman gave birth to a live infant with a congenital anomaly. No serious AEFIs or pIMDs were considered to be related to the vaccination. In Chinese women aged 9–45 years, immunization with the Cervarix three-dose schedule was well tolerated. Overall, no safety concerns were identified, although rare adverse events may have been missed due to the study sample size. Clinical trial registration: NCT03438006.

Cost-effectiveness of human papillomavirus (HPV) vaccination in Burkina Faso: a modelling study

BackgroundAfrica has some of the highest cervical cancer incidence and mortality rates globally. Burkina Faso launched a human papillomavirus (HPV) vaccination programme for 9-year-old girls in 2022 with support from Gavi, the Vaccine Alliance (Gavi). An economic evaluation of HPV vaccination is required to help sustain investment and inform decisions about optimal HPV vaccine choices.MethodsWe used a proportionate outcomes static cohort model to evaluate the potential impact and cost-effectiveness of HPV vaccination for 9-year-old girls over a ten-year period (2022–2031) in Burkina Faso. The primary outcome measure was the cost (2022 US$) per disability-adjusted life year (DALY) averted from a limited societal perspective (including all vaccine costs borne by the government and Gavi, radiation therapy costs borne by the government, and all other direct medical costs borne by patients and their families). We evaluated four vaccines (CERVARIX®, CECOLIN®, GARDASIL-4®, GARDASIL-9®), comparing each to no vaccination (and no change in existing cervical cancer screening and treatment strategies) and to each other. We combined local estimates of HPV type distribution, healthcare costs, vaccine coverage and costs with GLOBOCAN 2020 disease burden data and clinical trial efficacy data. We ran deterministic and probabilistic uncertainty analyses.ResultsHPV vaccination could prevent 37–72% of cervical cancer cases and deaths. CECOLIN® had the most favourable cost-effectiveness (cost per DALY averted < 0.27 times the national gross domestic product [GDP] per capita). When cross-protection was included, CECOLIN® remained the most cost-effective (cost per DALY averted < 0.20 times the national GDP per capita), but CERVARIX® provided greater health benefits (66% vs. 48% reduction in cervical cancer cases and deaths) with similar cost-effectiveness (cost per DALY averted < 0.28 times the national GDP per capita, with CECOLIN® as the comparator). We estimated the annual cost of the vaccination programme at US$ 2.9, 4.1, 4.4 and 19.8 million for CECOLIN®, GARDASIL-4®, CERVARIX® and GARDASIL-9®, respectively. A single dose strategy reduced costs and improved cost-effectiveness by more than half.ConclusionHPV vaccination is cost-effective in Burkina Faso from a limited societal perspective. A single dose strategy and/or alternative Gavi-supported HPV vaccines could further improve cost-effectiveness.

Treatment of Cervical Precancers is the Major Remaining Challenge in Cervical Screening Research.

Deepening understanding of cervical cancer pathogenesis has yielded one-dose prophylactic human papillomavirus (HPV) vaccines and accurate HPV-based cervical screening tests. Knowing the heterogeneous carcinogenic potential of the individual high-risk HPV types permits prioritization of vaccination and screening strategies. However, "correct" (i.e., safe and effective) treatment of women found to have precancer is still undefined, forcing reliance on one or more rounds of untargeted destructive/excisional treatment. Both over-treatment and under-treatment are common results. Until safe and effective anti-HPV therapies are invented, defining optimal destructive/excisional treatment of precancer remains a fundamental and under-researched challenge, especially in resource-constrained settings. See related article by King et al., p. 681.

Exploring HPV as an Etiologic Factor for Breast Cancer

Abstract Introduction/Objective Breast ducts communicate with skin, which can expose one to infectious agents. Recent studies demonstrate differences between breast microbiome in normal tissues versus tumor, suggesting a potential role in carcinogenesis. Human Papilloma Virus (HPV) is the etiologic factor in numerous cancers, and studies suggest it may play a role in breast carcinoma. A recent case report identified an analogue to HPV-related multiphenotypic sinonasal carcinoma in the breast. This sinonasal tumor, closely associated with HPV type 33, consists of adenoid cystic-like morphology, basaloid and/or squamous cytology and multi-lineage differentiation (ductal and myoepithelial). Our aim was to determine if HPV is a driver of breast carcinomas with the outlined phenotype by testing with immunohistochemistry (IHC) for p16 and in-situ hybridization (ISH) for High Risk HPV (HR-HPV) E6/E7 mRNA. Methods/Case Report Breast cases from 2010- June 2022 were searched with the terms “adenoid cystic,” “myoepithelial differentiation,” or “basaloid.” Cases of adenoid cystic carcinoma with a diagnostic fusion were excluded. Those with basaloid and/or squamous morphologic features containing ductal and myoepithelial differentiation proven by IHC were included. Nine identified cases were submitted for p16 IHC and HR-HPV ISH. Results (if a Case Study enter NA) Patients ranged in age from 50 to 85. No cases resulted with positive HR-HPV, however all cases displayed staining for p16. All cases with benign breast tissue (6/9) exhibited some p16 positivity within luminal and myoepithelial cells. Conclusion HR-HPV ISH is a sensitive test; however, no cases were positive. Most tumors and benign breast expressed p16 in some form. p16 in basal-like breast cancer has been described, but only 3/7 cases with biomarkers were triple negative. Accordingly, p16 is not a reliable screening tool if detection of HPV becomes clinically relevant in the future. In this series, the phenotypic features assessed do not appear to be consistent harbingers of HPV infection. More studies are needed to assess the breast microbiome and oncogenic organisms to identify potential new therapeutic targets.

Detection of high-risk HPV 16 genotypes in cervical cancers using isothermal DNA amplification with electrochemical genosensor

Cervical cancer emerges as the third most prevalent types of malignancy among women on a global scale. Cervical cancer is significantly associated with the persistent infection of human papillomavirus (HPV) type 16. The process of diagnosing is crucial in order to prevent the progression of a condition into a malignant state. The early detection of cervical cancer through initial stage screening is of the utmost significance in both the prevention and effective management of this disease. The present detection methodology is dependent on quantitative polymerase chain reaction (qPCR), which necessitates the use of a costly heat cycler instrument. In this study, we report the development of an electrochemical DNA biosensor integrated with an isothermal recombinase polymerase amplification (RPA) reaction for the detection and identification of the high-risk HPV-16 genotype. The electrochemical biosensor exhibited a high degree of specificity and sensitivity, as evidenced by its limit of detection (LOD) of 0.23 copies/μL of HPV-16 DNA. The validity of this electrochemical platform was confirmed through the analysis of 40 cervical tissues samples, and the findings were consistent with those obtained through polymerase chain reaction (PCR) testing. Our straightforward electrochemical detection technology and quick turnaround time at 75 min make the assay suitable for point-of-care testing in low-resource settings.

Cervical Cancer Stages, Human Papillomavirus Integration, and Malignant Genetic Mutations: Integrative Analysis of Datasets from Four Different Cohorts

Cervical cancer represents a significant global health concern, stemming from persistent infections with high-risk types of human papillomavirus (HPV). The understanding of cervical cancer’s clinical correlates, risk factors, molecular mechanisms, stages, and associated genetic mutations is important for early detection and improved treatment strategies. Through integrated analysis of clinical and molecular datasets, this study aims to identify key factors that are overlapping and distinct across four cohorts of different races and regions. Here, datasets from four distinct cohorts of patients from Uganda (N = 212), the United States of America (USA) (N = 228), China (N = 106), and Venezuela (N = 858) were examined to comprehensively explore the relationships between cervical cancer stages, HPV types (clades), productive HPV integration, and malignant genetic mutations. Cohort-specific findings included the occurrence frequencies of cervical cancer stages and grades. The majority of patients from the USA and China were diagnosed with stages I and II, while those from Uganda were diagnosed with stages II and III, reflecting levels of awareness and the availability of HPV vaccines and screening services. Conversely, cervical cancer and its stages were positively correlated with HPV types (clades), HPV integration, and risk-factor habits across the cohorts. Our findings indicate that the more common squamous cervical cancer can be potentially due to productive HPV16 (clade 9) integration. At the molecular level, pathways related to HPV infection, cancer-related conditions, and viral carcinogenesis were among the most significant pathways associated with mutated genes in cervical cancer (across cohorts). These findings collectively corroborate the prominent role of HPV infection and integration leading to genetic mutation and hence to the development of cervical cancer and its stages across patients of distinct races and regions.

Erratum: Prevalence and distribution of selected cervical human papillomavirus types in HIV infected and HIV uninfected women in South Africa, 1989–2021: A narrative review

Erratum: Prevalence and distribution of selected cervical human papillomavirus types in HIV infected and HIV uninfected women in South Africa, 1989–2021: A narrative review

Epidemiology, Molecular Pathogenesis, Immuno-Pathogenesis, Immune Escape Mechanisms and Vaccine Evaluation for HPV-Associated Carcinogenesis.

Human papillomavirus (HPV) is implicated in over 90% of cervical cancer cases, with factors like regional variability, HPV genotype, the population studied, HPV vaccination status, and anatomical sample collection location influencing the prevalence and pathology of HPV-induced cancer. HPV-16 and -18 are mainly responsible for the progression of several cancers, including cervix, anus, vagina, penis, vulva, and oropharynx. The oncogenic ability of HPV is not only sufficient for the progression of malignancy, but also for other tumor-generating steps required for the production of invasive cancer, such as coinfection with other viruses, lifestyle factors such as high parity, smoking, tobacco chewing, use of contraceptives for a long time, and immune responses such as stimulation of chronic stromal inflammation and immune deviation in the tumor microenvironment. Viral evasion from immunosurveillance also supports viral persistence, and virus-like particle-based prophylactic vaccines have been licensed, which are effective against high-risk HPV types. In addition, vaccination awareness programs and preventive strategies could help reduce the rate and incidence of HPV infection. In this review, we emphasize HPV infection and its role in cancer progression, molecular and immunopathogenesis, host immune response, immune evasion by HPV, vaccination, and preventive schemes battling HPV infection and HPV-related cancers.

Epidemiology of genital human papillomavirus infections in sequential male sex partners of young females

ObjectivesCouple-based studies have considered human papillomavirus (HPV) transmission between current heterosexual partners (male↔female). Using data from young women and their sequential male partners, we analysed HPV transmission from upstream sexual partnerships (male 1↔female) to downstream sex partners (→male 2). MethodsAmong 502 females enrolled in the HPV Infection and Transmission among Couples through Heterosexual activity study (2005–2011, Montréal, Canada), 42 brought one male sex partner at baseline (male 1) and another during follow-up (male 2). Female genital samples, collected at six visits over 24 months, and male genital samples, collected at two visits over 4 months, were tested for 36 HPV types (n = 1512 detectable infections). We calculated observed/expected ratios with 95% CIs for type-specific HPV concordance between males 1 and 2. Using mixed-effects regression, we estimated ORs with 95% CIs for male 2 testing positive for the same HPV type as male 1. ResultsDetection of the same HPV type in males 1 and 2 occurred 2.6 (CI 1.9–3.5) times more often than chance (29 instances observed vs. 10.95 instances expected). The OR for male 2 positivity was 4.2 (CI 2.5–7.0). Adjusting for the number of times the linking female tested positive for the same HPV type attenuated the relationship between male 1 and 2 positivity, suggesting mediation. ConclusionsHigh type-specific HPV concordance between males 1 and 2 confirms HPV's transmissibility in chains of sequential sexual partnerships. HPV positivity in an upstream partnership predicted positivity in a downstream male when the linking female partner was persistently positive.

Human papillomavirus type 16 E6 promotes cervical cancer proliferation by upregulating transketolase enzymatic activity through the activation of protein kinase B.

Over 99% of precancerous cervical lesions are associated with human papillomavirus (HPV) infection, with HPV types 16 and 18 (especially type 16) found in over 70% of cervical cancer cases globally. E6, a critical HPV gene, triggers malignant proliferation by degrading p53; however, this mechanism alone cannot fully explain the oncogenic effects of HPV16 E6. Therefore, we aimed to investigate new targets of HPV oncogenic mechanisms. Our results revealed significant changes in nonoxidative pentose phosphate pathway (PPP) metabolites in HPV16-positive cells. However, the role of nonoxidative PPP in HPV-associated cell transformation and tumor development remained unexplored. In this study, we investigated the impact and mechanisms of HPV16 E6 on cervical cancer proliferation using the HPV-negative cervical cancer cell line (C33A). HPV16 E6 was found to promote cervical cancer cell proliferation both in vitro and in vivo, activating the nonoxidative PPP. Transketolase (TKT), a key enzyme in the nonoxidative PPP, is highly expressed in cervical cancer tissues and associated with poor prognosis. HPV16 E6 promotes cervical cancer cell proliferation by upregulating TKT activity through the activation of AKT. In addition, oxythiamine (OT), a TKT inhibitor, hindered tumor growth, with enhanced effects when combined with cisplatin (DDP). In conclusion, HPV16 E6 promotes cervical cancer proliferation by upregulating TKT activity through the activation of AKT. OT demonstrates the potential to inhibit HPV16-positive cervical cancer growth, and when combined with DDP, could further enhance the tumor-suppressive effect of DDP.

Prevalence and Risk Assessment of Human Papillomavirus Infection in a Bengali Cohort

Cervical cancer is a notable cause of mortality and morbidity among women of reproductive age. Human papillomavirus (HPV) is the leading cause of cervical cancer among women. Among 170 types of HPV; HPV-16 and -18 are responsible for cervical cancer. The overexpression of oncoproteins E6 and E7 are predominantly responsible for causing neoplasia. The presence of koilocytosis/koilocytotic atypia is the diagnostic point of HPV infection in pap smears. To identify the circulating types of HPV and determine the various risk factors associated with HPV infection, 100 vaginal biopsies or swabs were taken from patients suspected with cervical cancer, and qualitative and semi-quantitative real-time PCR were performed. PCR primers (GP5+/GP6+) based on a conserved region of the HPV-L1open reading frame(ORF) gene were used for the detection of HPV strains, while another set of primers was used for detecting the E6 gene (HPV-16) and E7 gene (HPV-18). The results showed an HPV infection rate of 23%. Furthermore, the prevalent genotype was found to be HPV-16 (73.91%), followed by HPV-18 (26.1%), while mixed infections of both HPV-16 and -18 accounted for 21.74%. In addition, an age of above 45 years, multiple pregnancies, low socioeconomic status, postmenopausal state, anemia, and early coitarche were significantly associated with HPV infection. These results provide the basis for the formulation of an appropriate strategy for disease monitoring to determine the frequency and distribution pattern of HPV infection.

Capillary-driven microfluidic device integrating recombinase polymerase amplification for human papillomavirus detection

Nucleic acid amplification tests (NAATs) have been widely used in clinical diagnosis. However, current NAATs lack of user-friendly operation, require expensive systems and rely on laboratory-based methods. Here, we present low-cost and easy-to-fabricate capillary-driven microfluidic device for detecting DNA targeting of Human papillomavirus (HPV) type 16. The combination of recombinase polymerase amplification (RPA), reagent mixing, and detection of amplified DNA can be completed in a single microfluidic platform. We made the microfluidic circuit by stacking layers of transparent film and double-sided adhesive film, creating capillary in the gap between two layers of transparent film that drives the flow. The different channel height in each part of microfluidic channel creates push valve that allowed sequential fluid flow to be stopped for RPA reaction for 30 min. Users open the valve by pressing it to transfer RPA product into the detection system and automatically mix with SYBR Green I for fluorometric readout. The microfluidic device could detect HPV 16 DNA within the range of 0.002–1.0 ng/μL, with a detection limit of 0.24 pg/μL. The device demonstrated great performance when applied to clinical sample. The innovative device design transforms NAATs development for real-world point-of-care use through streamlined single-device operation.

Development of a touchdown droplet digital PCR assay for the detection and quantitation of human papillomavirus 16 and 18 from self-collected anal samples

ABSTRACT Broad-spectrum droplet digital polymerase chain reaction (ddPCR) assays can be used to quantitate multiple human papillomavirus (HPV) types. However, the presence of nucleotide mismatches at the primer binding sites may result in different optimal annealing temperatures and, consequently, under detection of some HPV types. Touchdown PCR uses decreasing annealing temperature over the first PCR cycles allowing for specific and efficient amplification of the target sequence. Here, as a proof-of-concept, we assessed if touchdown ddPCR (TD-ddPCR) using broad-spectrum oligonucleotides and genotype-specific probes targeting HPV L1 can be used to quantitate HPV. We tested our hypothesis using HPV positive cell lines and anal samples which potentially contain PCR inhibitors. Using serial dilutions of HPV16 and HPV18 DNA, the TD-ddPCR assays were performed with linearity across the dilution series (Pearson’s correlation r = 0.9999) and detected one copy of both HPV types, with no cross-reactivity to 27 other low-risk and high-risk HPV types. The PCRs were highly reproducible, with inter- and intra-assay coefficient of variations ranging 2.0–6.3% for HPV16 and 4.9–11.6% for HPV18. Testing self-collected anal samples positive for HPV16 ( n = 29) or HPV18 ( n = 33) and those negative for both HPV types ( n = 22) with the ddPCR assay and Seegene Anyplex II HPV28 (Seegene, TD-ddPCR) showed high agreements between the two assays. In conclusion, HPV broad-spectrum primers containing mismatches at their target binding sites and a touchdown thermal cycling approach resulted in sensitive and specific amplification of HPV genome using ddPCR. The assay has potential clinical diagnostic applications for detection, quantitation, and monitoring of anal HPV infections. IMPORTANCE The quantity of the human papillomavirus (HPV) is associated with disease outcome. We designed an accurate and precise digital PCR assay for quantitating HPV in anal samples, a sample type that is typically problematic due to the presence of PCR inhibitors.

Development of a proficiency testing program for HPV serology assays used to evaluate antibody responses in vaccine trials

In this study, a proficiency panel was created for evaluation of assay performance and inter- and intra-laboratory assay comparisons, especially the ability to accurately measure negative, low, intermediate, and high levels of HPV type-specific antibodies. Comprised of 80 deidentified samples, this panel is designed for individual labs to evaluate assay performance characteristics on a biennial basis, to promote standardization of methodology and harmonization of data from human papillomavirus (HPV) serology tests in vaccine trials. The proficiency panel was qualified using 2 types of assays (singleplex Enzyme-Linked Immunosorbent Assays [ELISAs] or Multiplex antibody-binding assays and Pseudovirion-based neutralization assays [PBNAs]) in 10 laboratories from 7 countries, monitoring HPV antibody responses for up to 9 HPV types and using 3 different analysis methods. Sensitivity, specificity, and correlations (concordance, accuracy, and precision) were evaluated for each HPV type. In laboratories that tested all 80 samples, results from most (74/80) samples were reported with 100% accuracy across all 9 HPV types. The average sensitivity and specificity for singleplex and multiplex antibody binding assays ranged from 86.7% to 98.3% (sensitivity) and 84.2% to 94.3% (specificity), while the average sensitivity and specificity for the Pseudovirion (PsV)-based neutralization assays (PBNA) ranged from 87.6% to 99.4% (sensitivity) and 52.4% to 94.4% (specificity). This proficiency panel will help with assessing performance characteristics of HPV serology assays used in clinical trial studies and assure the data generated from these assays is harmonized.

Advances on two serological assays for human papillomavirus provide insights on the reactivity of antibodies against a cross-neutralization epitope of the minor capsid protein L2.

A second generation of prophylactic human papillomavirus (HPV) vaccines based on the minor capsid protein L2 has entered clinical trials as promising alternative to meet the gaps left out by the current vaccines concerning type-restricted protection, high costs and low penetrance in immunization programs of lowand middle-income countries. Most of the serological assays available to assess anti-HPV humoral responses are, however, not well suited for measuring vaccine-induced anti-L2 antibody responses. In this work, we have advanced our automated, purely add-on High-Throughput Pseudovirion-Based Neutralization Assay (HT-PBNA) in an L2-oriented approach for measuring antibody-mediated neutralization of HPV types 6/16/18/31/33/52/58. With the optimized settings, we observed 24- to 120-fold higher sensitivity for detection of neutralizing Ab to the L2 protein of HPV6, HPV16, HPV18, and HPV31, compared to the standard HT-PBNA. Alternatively, we have also developed a highly sensitive, cell-free, colorimetric L2-peptide capture ELISA for which the results were strongly concordant with those of the advanced neutralization assay, named HT-fc-PBNA. These two high-throughput scalable assays represent attractive approaches to determine antibody-based correlates of protection for the HPV L2 vaccines that are to come.

Immunogenicity and safety of a new quadrivalent HPV vaccine in girls and boys aged 9–14 years versus an established quadrivalent HPV vaccine in women aged 15–26 years in India: a randomised, active-controlled, multicentre, phase 2/3 trial

Immunogenicity and safety of a new quadrivalent HPV vaccine in girls and boys aged 9–14 years versus an established quadrivalent HPV vaccine in women aged 15–26 years in India: a randomised, active-controlled, multicentre, phase 2/3 trial

Circulating cell-free HPV DNA is a strong marker for disease severity in cervical cancer.

For cervical cancer (CC), circulating cell-free HPV DNA (ccfHPV) may establish disease severity. Furthermore, HPV integration has been correlated to viral load and survival. In this study, pre-treatment plasma from 139 CC cases (50 primary surgery patients, 22 primary surgery + adjuvant oncological therapy patients, and 67 primary oncological therapy patients) was collected (2018-2020). Furthermore, plasma from 25 cervical intraepithelial neoplasia grade 3 patients and 15 healthy women (negative controls) were collected. Two next-generation sequencing (NGS) panels were used to establish ccfHPV presence and human papillomavirus type 16 (HPV16) integration status. ccfHPV was detected in four primary surgery (8.0%), eight primary surgery + adjuvant oncology (36.4%), and 54 primary oncology (80.6%) patients. For primary oncology patients with HPV16-related cancer (n = 37), more ccfHPVneg than ccfHPVpos patients had HPV16 integration (P = 0.04), and in patients with HPV16 integration (n = 13), ccfHPVpos patients had higher disease stages than ccfHPVneg patients (P = 0.05). In summary, ccfHPV presence is related to disease severity and may add to the debated Sedlis criteria used for identifying patients for adjuvant oncological therapy. However, ccfHPV detection is influenced by HPV integration status and disease stage, and these factors need to be considered in ccfHPVneg patients.

Ecological diversity profiles of non-vaccine-targeted HPVs after gender-based community vaccination efforts

The long-term effect of population-level human papillomavirus (HPV) vaccination on the viral ecology of the untargeted HPVs is poorly understood. We performed an 8-year follow-up of 33 communities randomized to gender-neutral HPV16/18 vaccination, girls-only HPV16/18 vaccination, and control communities without HPV vaccination. The 1992/93 and 1994 birth cohorts were invited in school years 2007/8 and 2008/9. Follow-up cervico-vaginal sampling at 18 and 22 years of age, 4 and 8 years post-vaccination, respectively, were attended by 11,396 and 5,602 participants. HPV types 6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68 were genotyped and used for the community-level ecological diversity estimations. Gender-neutral vaccination communities with a stronger herd immunity than girls-only vaccination communities show a significantly increased HPV α-diversity (p=1.1×10-8) from 4 to 8 years post-vaccination, despite the clearance of the vaccine-targeted HPVs in these communities. This likely sign of niche occupation by the non-vaccine-targeted HPVs will potentially affect the future cervical cancer screening programs but should not interfere with the WHO mission to eliminate cervical cancer.

HPV co-infections with other pathogens in cancer development: A comprehensive review.

High-risk human papillomaviruses (HR-HPVs) cause various malignancies in the anogenital and oropharyngeal regions. About 70% of cervical and oropharyngeal cancers are caused by HPV types 16 and 18. Notably, some viruses including herpes simplex virus, Epstein-Barr virus,and human immunodeficiency virusalong with various bacteria often interact with HPV, potentially impacting its replication, persistence, and cancer progression. Thus, HPV infection can be significantly influenced by co-infecting agents that influence infection dynamics and disease progression. Bacterial co-infections (e.g., Chlamydia trachomatis) along with bacterial vaginosis-related species also interact with HPV in genital tract leading to viral persistence and disease outcomes. Co-infections involving HPV and diverse infectious agents have significant implications for disease transmission and clinical progression. This review explores multiple facets of HPV infection encompassing the co-infection dynamics with other pathogens, interaction with the human microbiome, and its role in disease development.