Human Papillomavirus Infection Research Articles

Status of HPV disease and vaccination programmes in LMICs: Introduction to special issue

Sexually transmitted human papillomavirus (HPV) infections are extremely common in both men and women and while most will clear naturally, some may progress to cervical cancer and other cancers. Despite the availability of prophylactic vaccines and well-established screening and treatment practices, the global burden of HPV-related disease remains high, particularly in low-and-middle-income countries (LMICs). We outline the current global epidemiology of cervical cancer disease incidence and mortality, with the highest burden in Africa and Asia. As part of a strategy to eliminate cervical cancer as a public health problem, the WHO recommends a 3-fold approach combining the use of prophylactic vaccines with cervical cancer screening and treatment. This overview focuses on the globally available HPV vaccines and current status of vaccine introduction in LMICs. We describe decreased HPV vaccination coverage in recent years and highlight the need for emphasis on new vaccine introductions and existing vaccine programme strengthening in order to reach goals for the elimination of cervical cancer as a public health problem. It is estimated that US$3.20 will be returned on each dollar invested in cervical cancer prevention efforts through 2050 [1]. Success for these initiatives centers on strategic vaccine delivery and collaborations that foster political support and engagement with civil society organisations and educational sector stakeholders. Recent increases in vaccine supply and single-dose efficacy evidence pave the way for cervical cancer elimination through vaccination coupled with screening and treatment. Subsequent manuscripts in this supplement will outline case studies and lessons from two symposia held in Africa and South Asia by the Coalition to Strengthen the HPV Immunization Community in 2022 including evidence for a one-dose strategy, the challenges of maintaining vaccine programmes during the COVID-19 pandemic, and progress in cervical cancer screening programmes.

Clinical, Histological, and HPV-Related Factors Associated to Diffuse Presentation of Exophytic Nasal Papillomas

Background: Sinonasal exophytic papillomas (SNEP) are benign tumours arising from nasal mucosa. Human papillomavirus (HPV) infection seems to be related to the aetiology of a fraction of SNEP cases. SNEP presentation can be focal (FSNEP) or diffuse (DSNEP), but factors related to focal or diffuse presentation have not yet been well ascertained. This study aimed to analyse clinical, histological, and HPV-related differences between FSNEP and DSNEP. Methods: A retrospective cohort of 18 patients with SNEP from our centre were evaluated. Demographic, clinical and follow-up data were collected. All samples were subject to histopathological evaluation, DNA quality control, HPV-DNA detection, and viral load assessment. Univariate analyses were performed to evaluate differences between FSNEP and DSNEP. Results: Twelve SNEP patients were included in the final analysis. Seven patients had a diffuse nasal presentation, being younger than patients affected with FSNEP (42.7 years vs. 65.2 years, p = 0.019). The nasal septum was significantly more affected in DSNEP than in FSNEP (85.7% vs. 20%, p = 0.029). HPV-DNA was detected more frequently (100%) in DSNEP (HPV11 in six cases, HPV6 in one case) than in FSNEP (40%, p = 0.045, HPV6 in two cases). The median viral load among HPV6-positive samples was 626.8 virus/cell for FSNEP and 80.2 for DSNEP, and among HPV11-positive samples was 1673.7 for DSNEP. Recurrences were more frequent in the diffuse than in the focal group (85.7% vs. 20%, p = 0.029). Conclusions: The diffuse presentation of SNEP seems to be related to younger patients, nasal septum involvement, HPV infection, mostly HPV11, and a higher risk of recurrence.

Prevalence of vaginal and cervical HPV infection among 35-year age cohort ever-married women in Kalutara district of Sri Lanka and the validity of vaginal HPV/DNA specimen as a cervical cancer screening tool: a cross-sectional study.

Cervical cancer is the 2nd most common female cancer among Sri Lankan females and is almost associated with sexually transmitted cervicovaginal human papillomavirus (HPV) infection. The study objectives were to determine the prevalence of vaginal and cervical HPV infection among 35year old ever-married women and assess the validity of primary healthcare provider-collected vaginal HPV/DNA specimens as a cervical cancer screening tool to improve the coverage of the programme. A descriptive cross-sectional study was carried out from the 1st of September 2018 to the 31st of January 2019. Ever-married women 35 years of age in Kalutara district were the study population. Two women from each Public Health Midwife area (n = 413) were selected randomly from the relevant area eligible families register/s. HPV/DNA cervical specimen and vaginal specimen collection (n = 621) were carried out. Specimens were screened by the Cobas 4800 HPV/DNA automated Polymerase Chain Reaction (PCR) machine. Participants' profiles were recorded by the research assistants using an interviewer-administered questionnaire. The overall prevalence of vaginal and cervical HPV infection was 7.08% (95% CI; 5.2-9.4%) and 6.12% (95% CI; 4.26-8.3%) respectively. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic accuracy, and the kappa coefficient of the vaginal HPV/DNA screening method vs. cervical HPV/DNA screening method were 100%, 98.9%, 86.4%, 100%, 99% and 0.92 respectively. Vaginal HPV/DNA specimen screening method can be used as a cervical cancer screening tool due to its high validity. Pilots of the feasibility should be set up before the regional or national rollout of vaginal sampling strategies.

Retrospective analysis of HPV infection: Cotesting and HPV genotyping in cervical cancer screening within a large academic health care system.

In 2019, the American Society for Colposcopy and Cervical Pathology introduced fundamental shifts toward "risk-based" guidelines, with human papillomavirus (HPV) genotyping as a principal test for investigating squamous intraepithelial lesions. This study aims to provide practice-based evidence and supplement the updated guidelines by investigating HPV demographic distribution and uncovering the pathological features of high-grade squamous intraepithelial lesions (HSILs) caused by high-risk HPV (hrHPV) subtypes. Patients who underwent Papanicolaou screening and HPV testing in two hospital systems over the course of 4 years were recruited. The cytology results were categorized on the basis of the 2014 Bethesda classification. DNA sequences of 14 types of hrHPV were detected by Aptima test. The histological features of HSILs caused by different subtypes were compared between biopsies and excisions. A total of 63,709 cases were included. The HPV prevalence was 14.70%, predominantly in the 30 to 39-year-old age group, with slightly higher rates observed in African Americans. There was no significant racial distribution difference between HPV 16/18/45 and other types. HPV 16/18/45 infection was directly correlated with the severity of abnormal cytology, although the other subtypes were the major causes of cytological abnormalities. The trend for HPV prevalence was consistent across calendar years, and was associated with 8.77% negative for intraepithelial lesion or malignancy, 30.46% atypical squamous cell of undetermined significance, 64.62% low-grade squamous intraepithelial lesion, 66.75% atypical squamous cell-cannot exclude a high-grade squamous intraepithelial lesion, and 91.80% HSIL. Furthermore, 29.09% of HSILs associated with other subtypes were not detectable on subsequent resections. Given the HPV demographic distribution and the histological features of HSILs caused by different subtypes, cotesting with reflex HPV genotyping in specific populations, or expanding the subtypes in the primary HPV screening test, should be considered.

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

IntroductionImmunocompromised 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).MethodsOpen-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.Results125 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.Conclusion4vHPV 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.

The dietary inflammatory index (DII®) and human papillomavirus infection: a cross-sectional study of US women

BackgroundDiet may influence susceptibility of human papillomavirus (HPV) infection by affecting inflammation and immunity. However, the association between HPV infection and the inflammatory potential of diet has not been investigated. The research aimed to examine the correlation between HPV status and the dietary inflammatory index (DII®).MethodsWe utilized data from the National Health and Nutrition Examination Survey (NHANES) 2003–2016 to investigate the correlation between DII and HPV status among 9,256 women aged 18–59 years. DII scores were calculated based on 24-hour dietary recall interviews. The association between HPV status and DII was analyzed using weighted logistic regression and restricted cubic spline (RCS).ResultsWomen with HPV infection exhibited higher DII scores than those without HPV infection. An increased likelihood of HPV infection was found to be significantly associated with higher DII scores (OR = 1.05, 95% CI: 1.01–1.09, P = 0.021), after full multivariate adjustment. Compared with the lowest tertile of DII scores, the ORs (95% CIs) for HPV infection were 1.20 (1.01, 1.42) and 1.27 (1.07, 1.51) for the second and third tertiles, respectively (P for trend = 0.006). RCS analysis showed a U-shaped relationship between DII and HPV infection, with a breakpoint identified at 0.13.ConclusionsOur findings suggest that a pro-inflammatory diet is associated with an increased likelihood of HPV infection among women in the United States. Dietary interventions to reduce inflammation may help prevent HPV infection and related diseases.

Human papillomavirus infection is associated with increased risk of new-onset hidradenitis suppurativa: a population-based cohort study

BackgroundThe exact cause of hidradenitis suppurativa (HS) remains unclear, though emerging research suggests a link between infectious agents and inflammatory skin diseases. The association between human papillomavirus (HPV) infection and HS development, however, has not been studied. ObjectiveTo evaluate the risk of incident HS in HPV infection patients. MethodsUsing the TriNetX research network, we conducted a retrospective cohort study of patients diagnosed with HPV and matched controls. Propensity score matching adjusted for variables like age, sex, race, BMI, comorbidities, and lifestyle factors. The primary outcome was new-onset HS, analyzed across demographic and clinical factors. Hazard ratios with 95% confidence intervals (95% CI) were calculated to assess risk. ResultsAfter matching, both the HPV and control cohorts included 582,007 patients. HPV-infected individuals had a significantly higher risk of developing HS (HR: 1.356, 95% CI: 1.290-1.427). This increased risk was consistent across various demographic and clinical groups. Sensitivity analyses confirmed the robustness of these findings. LimitationsRetrospective cohort design. ConclusionsHPV infection is linked to a higher risk of HS, suggesting a potential association. Further research is required to validate these results and assess their impact in different populations and clinical settings but could also elucidate a potential impact of other infections involved in the pathogenesis of HS.

HPV infection status among women of all ages in Jinshan District, Shanghai.

We explored the prevalence of human papillomavirus (HPV) infection among women in Jinshan District, Shanghai. We analyzed all HPV testing samples sent from our unit between December 2023 and April 2024. We reported the HPV prevalence overall, by age, and by subtype. In total, 3788 women aged 16 to 90 years had HPV test results. The prevalence of infection with any HPV subtype was 17.9%. The HPV prevalence by age group was: ≤30 years, 15.4%; 31-40 years, 14.7%; 41-50 years, 17.0%; 51-60 years, 22.4%; >60 years, 31.0%. Among HPV-positive women, 80.6% had infection with one subtype, 16.4% had dual infection, and 3.1% had three or more subtypes detected. We found 640 cases (16.9%) of infection with high-risk HPV subtypes and 139 cases (5.04%) of infection with low-risk HPV subtypes. The most common high-risk subtypes were HPV 52, 53, 58, and 16; the most common low-risk subtypes were HPV 81, 70, and 42. We detected ≥1 HPV subtype among most women in our study. The prevalence of HPV was lowest in younger women and highest in women age >60 years. Tailored strategies for older women are needed to prevent HPV infection and cervical cancer.

Population-level impact of switching to 1-dose human papillomavirus vaccination in high-income countries: examining uncertainties using mathematical modeling.

A concern in high-income countries is that switching to 1-dose human papillomavirus (HPV) vaccination could cause a rebound in HPV infection and cervical cancer if 1-dose efficacy or duration were inferior to 2 doses. Using mathematical modeling and up-to-date trial-based data, we projected the population-level effectiveness of switching from 2-dose to 1-dose vaccination under different vaccine efficacy and duration assumptions in high-income countries. We used HPV-ADVISE (Agent-based Dynamic model for VaccInation and Screening Evaluation), a transmission-dynamic model of HPV infection and cervical cancer, varying key model assumptions to identify those with the greatest impact on projections of HPV-16 and cervical cancer incidence over time: 1) 1-dose vaccine efficacy and vaccine duration, 2) mechanisms of vaccine efficacy and duration over time, 3) midadult (>30 years of age) sexual behavior, 4) progression to cervical cancer among midadults, and 5) vaccination coverage and programs. In high-income countries, 1-dose vaccination would cause no appreciable rebound in HPV-16 infection, except for a limited rebound under the most pessimistic assumptions of vaccine duration (average, 25 years), because 1) the switch would occur when HPV prevalence is low because of high 2-dose vaccination coverage and 2) individuals would be protected during their peak ages of sexual activity (<35 to 40 years of age). Our model projects a more limited rebound in cervical cancer because of a shift to older age at infection, resulting in fewer life-years left to potentially develop cancer. Projections were robust when varying key model assumptions. High protection during peak ages of sexual activity in high-income countries would likely mitigate any potential rebounds in HPV infection and cervical cancer under the most pessimistic assumptions of 1-dose efficacy and duration.

Community intervention of a single-dose or 2-dose regimen of bivalent human papillomavirus vaccine in schoolgirls in Thailand: vaccine effectiveness 2 years and 4 years after vaccination.

With accumulating evidence of single-dose human papillomavirus (HPV) vaccine efficacy in young women, we conducted a community vaccine effectiveness study comparing HPV single-dose and 2-dose regimens (0 and 6 months) of a bivalent HPV vaccine among grade 8 schoolgirls (aged 13-14 years) in Thailand. In 2018, eligible grade 8 schoolgirls in Udon Thani (single dose) and Buri Ram (2 doses) provinces were offered HPV vaccine per assigned dose regimen. Concurrently, a cross-sectional survey for measuring baseline HPV prevalence was conducted in grade 10 (n = 2600) and grade 12 unvaccinated schoolgirls (n = 2000) in each province. HPV infection was assessed in first-void urine samples, tested by DNA polymerase chain reaction on the cobas 4800 system (Roche Molecular Diagnostics, Pleasanton, CA). All samples positive on the cobas system and an equal number of negative samples were also tested by Anyplex II HPV28 Detection (Seegene, Seoul, South Korea). The surveys were repeated in 2020 and 2022, when vaccinated grade 8 schoolgirls reached grade 10, and then subsequently grade 12, respectively. Vaccine effectiveness was estimated by comparing the weighted prevalence of HPV-16 or HPV-18 between grade-matched unvaccinated schoolgirls on the baseline survey (2018) and vaccinated schoolgirls in the year-2 (2020) and year-4 (2022) surveys. Adjustment methods were used in the analysis to account for potential differences in sexual behavior due to the noncontemporaneous comparison. The prevalence of HPV-16 and HPV-18 on the baseline survey among unvaccinated grade 10/grade 12 schoolgirls was 2.90% (95% confidence interval [CI] = 2.54% to 3.31%)/3.98% (95% CI = 3.52% to 4.49%) for Udon Thani and 3.87% (95% CI = 3.46% to 4.34%)/6.13% (95% CI = 5.56% to 6.75%) for Buri Ram. On the year-2 survey, the prevalence among vaccinated grade 10 schoolgirls was 0.57% (95% CI = 0.42% to 0.77%) for Udon Thani and 0.31% (95% CI = 0.21% to 0.47%) for Buri Ram. The 2-year postvaccination crude vaccine effectiveness for the single-dose regimen was estimated at 80.4% (95% CI = 73.9% to 86.9%), and for the 2-dose regimen at 91.9% (95% CI = 88.5% to 95.4%). On the year-4 survey, the prevalence among vaccinated grade 12 schoolgirls was 0.37% (95% CI = 0.25% to 0.56%) for Udon Thani and 0.28% (95% CI = 0.18% to 0.45%) for Buri Ram. Four-year postvaccination crude vaccine effectiveness for the single-dose regimen was estimated at 90.6% (95% CI = 86.6% to 94.6%) and for the 2-dose regimen was estimated at 95.4% (95% CI = 93.2% to 97.6%). All adjustment methods minimally affected vaccine effectiveness for the single-dose and 2-dose regimens. At 4 years after vaccination, the difference in crude vaccine effectiveness between the single-dose and 2-dose regimens was ‒4.79% (95% CI = ‒9.32% to ‒0.25%), meeting the study's noninferiority criteria. Our study demonstrated that both single-dose and 2-dose HPV vaccination significantly decreased HPV-16/18 point prevalence 2 years and 4 years after vaccination. Crude vaccine effectiveness at 4 years after vaccination was greater than 90% for both the single-dose and 2-dose regimens; the single-dose regimen was not inferior to the 2-dose regimen. These data show that a single dose of HPV vaccine provides high levels of protection when administered to schoolgirls younger than 15 years of age.

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.

Skin cancer incidence in Mexican renal transplant recipients: a cohort over 56 years.

Skin cancer is a primary health concern in renal transplant recipients (RTRs). Existing research mainly stems from North America, Europe, and Australia, with limited data from Latin America. This 56-year (1967-2023) retrospective cohort study explores skin cancer incidence in Mexican RTRs. Our objective was to assess the long-term incidence of malignant cutaneous neoplasms in Mexican RTRs. Over 56 years, 1642 RTRs (58% male) were studied. Median follow-up was 8.4 years; median age at transplantation was 32.6 years. Skin cancer incidence was 6.6% (95% CI: 5.5-7.9), with an incidence density rate of 6.5 (95% CI: 5.4-7.9) per 1000 person-years and a median latency of 9.8 years. Incidence increased with longer transplantation-related immunosuppression (TRI), with a relative risk for >30 years of TRI of 4.8 (95% CI: 2.6-9.1) for any skin cancer and 7.5 (95% CI: 3.8-14.6) for squamous cell carcinoma (SCC). SCC was the most common malignancy (76.1%), followed by basal cell carcinomas (BCC), with a 3.6:1 ratio. Metastatic SCC occurred in 6.5% of skin cancer patients, with a skin cancer-related mortality rate of 2.7%. Limitations of the study include its single-center and retrospective design and unassessed factors such as human papillomavirus infection and sun exposure. Our study provides unique insights into the epidemiology of skin cancer among Mexican RTRs. It constitutes the largest cohort of skin cancer cases among RTRs in Mexico and, to our knowledge, in Latin America. Despite the lack of recognition of a high skin cancer incidence in non-White RTRs, our 6.6% incidence underscores the need to enhance surveillance programs.

Immunometabolic Contributions of Atopobiaceae Family Members in Human Papillomavirus Infection, Cervical Dysplasia and Cancer.

In the cervicovaginal environment, HPV acquisition and cervical cancer progression are linked to non-Lactobacillus dominance, of which Atopobiaceae are key taxa. We hypothesize that Atopobiaceae modulates the cervicovaginal microenvironment to promote HPV persistence and progression to cancer. However, the extent to which Atopobiaceae impact the immunometabolic microenvironment is poorly understood. We investigated Atopobiaceae in a cohort of primarily Hispanic and non-Hispanic White women who were HPV-negative (n=20), HPV-positive (n=31) without dysplasia, diagnosed with cervical dysplasia (n=38), or newly diagnosed with invasive cervical carcinoma (n=9). Microbiome data was integrated with clinical and demographic surveys, immunoproteomics, and metabolomics data. Atopobiaceae identified were Fannyhessea vaginae, Fannyhessea massiliense, Fannyhessea species type 2, Lancefieldella deltae, and an unclassified species. A higher prevalence of Atopobiaceae was observed in women who were Hispanic and had higher gravidity and parity. F. species type 2 and F. vaginae were observed with infections of high-risk HPV genotypes 31 and 52. Atopobiacaeae were negatively correlated with Lactobacillus and positively correlated to Sneathia, Dialister, Anaerococcus, Prevotella, and Bifidobacterium/Gardnerella. Proinflammatory cytokines (IL-1α, IL-1β, IL-12, TNFα), immune checkpoint proteins (PD-L1, LAG3), and cancer biomarkers (CEA, MIF, TRAIL) were positively associated with Atopobiaceae-rich profiles. Pro-oncogenic metabolites, including 4-hydroxybutyrate and sphingosine, were also elevated in women colonized by Atopobiaceae. Our data implicate Atopobiaceae in lipid modulation, oxidative stress, inflammatory responses, and immune evasion, which may contribute to cancer. This study highlights a key family of pathogenic cervicovaginal bacteria that could be exploited to monitor HPV persistence and/or targeted to prevent HPV-mediated cancer.

Coexistence of aerobic vaginitis caused by Enterococcus faecalis and human papilloma virus (HPV) infection as a risk factor for the development of cervical intraepithelial lesions

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Aim&amp;lt;/strong&amp;gt; To determine the prevalence of aerobic vaginitis (AV) caused by &amp;lt;em&amp;gt;Enterococcus faecalis (E. faecalis)&amp;lt;/em&amp;gt; in human papilloma virus (HPV)-positive women with pathological Pap test and to determine the most prevalent HPV type associated with &amp;lt;em&amp;gt;E. faecalis&amp;lt;/em&amp;gt; infection.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Methods&amp;lt;/strong&amp;gt; This prospective study was conducted at the Gynaecology Centre &amp;quot;Dr. Mahira Jahić&amp;quot; Tuzla and Primary Health Care Centre Te&amp;amp;scaron;anj (Bosnia and Herzegovina) in the period between February 2023 and March 2024. The research included 200 women aged 25 to 50 years. The examined group consisted of 100 women with a pathological (examined group) and 100 with a normal (control group) Pap test result.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Results&amp;lt;/strong&amp;gt; Pathological Pap smears were found in 60 (out of 100; 60 %) women in the examined group: cervical intraepithelial neoplasia (CIN) 1 and CIN 2 &amp;amp;nbsp;in two women, respectively, CIN 3 in seven, atypical squamous cells of undetermined significance (ASCUS) in 29 and atypical squamous cells-high-grade cannot be excluded (ASC-H) in two women. Overall (both groups) prevalence of &amp;lt;em&amp;gt;E. faecalis&amp;lt;/em&amp;gt; was 25.5% (51women); in 45 (22.5%) women &amp;lt;em&amp;gt;E. faecalis&amp;lt;/em&amp;gt; was the only bacterial isolate, of which 42 (21%) in the examined group and three (1.5%) in the control group. High-risk HPV types were found in 62 (out of &amp;amp;nbsp;100; 62%) women with the pathological Pap smear test. The association of &amp;lt;em&amp;gt;E. faecalis&amp;lt;/em&amp;gt; and high-risk HPV positive women was found in 35 (35%) cases (moderately positive correlation; r=0.198).&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Conclusion&amp;lt;/strong&amp;gt; E. faecalis is very common in HPV 16 and 18 positive women and may represent a risk factor in the development of cervical intraepithelial lesions.&amp;lt;/p&amp;gt;

Prevalence of Human Papillomavirus-Associated Head and Neck Cancer in Rwanda: A 10-Year Review.

Head and neck cancer (HNC) is a significant global health burden, with late presentation leading to complex treatment. While human papillomavirus (HPV) infection has been implicated in HNC, data from low- and middle-income countries (LMICs) are limited. In this study, we investigated the prevalence and role of HPV in head and neck cancers diagnosed in Rwanda. A retrospective cross-sectional study was conducted using Rwanda Cancer Registry from January 2011 through December 2020. p16 immunohistochemistry as a surrogate for HPV was performed on a randomly selected case. p16-positive cases were genotyped. A total of 1001 patients with HNC were identified; 82% (n = 819) had squamous cell carcinoma. The mean age at diagnosis was 51.1 years, with a majority being males (58%). Oral cavity and lip (27%) were the most common primary cancer sites. Stage was unknown in most cases (75%, n = 747). HIV status was known in 33% (n = 334) of patients with 10% (n = 33) HIV-positive; 22% of 202 randomly selected cases were p16-positive; 34% of the p16-positive cases were oropharynx. PCR analysis of p16-positive cases showed 19% HPV positivity, and HPV16 was the most common high-risk HPV strain, and 55.5% were recorded HPV-positive by PCR. HNC cases in Rwanda have been increasing from 2011 to 2020, with a significant portion being HPV-positive. Strategies to implement routine testing for p16, especially in oropharynx cancer patients, improved preservation of tissue samples, collection of comprehensive information including cancer risk factors, staging, and treatment are needed in Rwanda.

The Impact of HPV Vaccination on Cervical Cancer in adolescent females: A narrative review

ABSTRACT To effectively prevent cervical cancer, a leading cause of global morbidity and mortality among women, widespread adoption of the HPV vaccine has a well-established link to human papillomavirus (HPV) infection. HPV vaccine must be the vaccine’s effectiveness in reducing HPV infections, and subsequent cervical lesions have been extensively demonstrated, marking a pivotal milestone in public health. Important research highlights the vaccine’s safety profile, allaying worries and promoting trust in its application. By targeting HPV strains responsible for a majority of cervical cancer cases, vaccination emerges as a strategic intervention to curb the burden of this malignancy. The strategy is used to search PubMed and Google Scholar, with only free full-text and English language study included. However, addressing existing misconceptions and ensuring equitable vaccine access remains imperative. Informed decision making is pivotal, necessitating comprehensive public health initiatives that educate communities about the vaccine’s benefits. Encouragingly, successful vaccination programs in various regions have demonstrated tangible reductions in HPV prevalence and cervical cancer incidence. This review concludes by emphasizing the urgent need for global collaboration to integrate HPV vaccination into routine immunization schedules, thereby fortifying the collective effort to mitigate cervical cancer’s impact. As a cost-effective, evidence-based strategy, widespread HPV vaccination stands as a linchpin in the ongoing battle against cervical cancer, promising a healthier future for women worldwide.

The anti-tumor efficacy of a recombinant oncolytic herpes simplex virus mediated CRISPR/Cas9 delivery targeting in HPV16-positive cervical cancer

Cervical cancer, often driven by high-risk human papillomavirus (HPV) infections such as HPV16 or HPV18, remains a leading cause of cancer-related deaths. HPV16, found in about 90% of cervical cancer patients, harbors key oncogenic related genes (E6, E7, E2, E5) and an upstream regulatory region (URR) that contribute to cancer progression. This study introduces a novel approach using a recombinant oncolytic herpes simplex virus type 1 (HSV-1) named SONC103, armed with a CRISPR/Cas9 gene editing system. The aim was to target and disrupt integrated HPV16 genes in cervical cancer cells. Results demonstrated SONC103's capability to specifically and effectively knock down HPV16 oncogenes, thereby reducing cell proliferation and promoting apoptosis. Analyses further revealed loss of HPV16 DNA probes in infected cells' chromosomes, significant regulation of cellular processes related to tumor apoptosis, and downregulation of E6/E7 oncoproteins while increasing tumor suppressor proteins P53 and pRB. Notably, SONC103 exhibited substantial inhibition of tumor growth in a murine xenograft cervical cancer model. This study showcases the potential of the recombinant oncolytic HSV-1 virus (SONC103) in combating HPV16-positive cervical cancer by targeting oncogenes and facilitating oncolysis.

The Potential Impact of a Single-Dose HPV Vaccination Schedule on Cervical Cancer Outcomes in Kenya: A Mathematical Modelling and Health Economic Analysis

Background: Human Papillomavirus (HPV) is the primary cause of cervical cancer. Single-dose HPV vaccination can effectively prevent high-risk HPV infection that causes cervical cancer and accelerate progress toward achieving cervical cancer elimination goals. We modelled the potential impact of adopting single-dose HPV vaccination strategies on health and economic outcomes in Kenya, where a two-dose schedule is the current standard. Methods: Using a validated compartmental transmission model of HPV and HIV in Kenya, we evaluated the costs from the payer’s perspective to vaccinate girls by age 10 with either one or two doses and increasing coverage levels (0%, 70%, 77%, 90%). Additionally, we modelled single-dose strategies supplemented with either catch-up vaccination of adolescent girls and young women or vaccination for all by age 10, funded with the first five-years of cost savings of switching from a two- to one-dose schedule. Costs and outcomes were discounted at 3% annually, and incremental cost-effectiveness ratios (ICERs) were calculated per disability-adjusted-life-year (DALY) averted. Results: All one-dose and the two-dose 90% coverage strategies were on the efficiency frontier, dominating the remaining two-dose strategies. The two-dose 90% coverage strategy had a substantially higher ICER (US$6508.80/DALY averted) than the one-dose 90% coverage (US$197.44/DALY averted). Transitioning from a two- to one-dose schedule could result in US$21.4 Million saved over the first five years, which could potentially fund 2.75 million supplemental HPV vaccinations. With this re-investment, all two-dose HPV vaccination scenarios would be dominated. The greatest DALYs were averted with the single-dose HPV vaccination schedule at 90% coverage supplemented with catch-up for 11–24-year-old girls, which had an ICER of US$78.73/DALYs averted. Conclusions: Considering the logistical and cost burdens of a two-dose schedule, a one-dose schedule for girls by age 10 would generate savings that could be leveraged for catch-up vaccination for older girls and accelerate cervical cancer elimination in Kenya.

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.

Vaccination strategies in a pair formation model for human papillomavirus infection: An optimal control approach

Vaccination strategies in a pair formation model for human papillomavirus infection: An optimal control approach