International Journal of STD & AIDS

Persistence of HPV in cervical smears of vaccinated WLWH support for combined molecular testing and cytology screening

Background Human papillomavirus (HPV) infection profoundly affects women living with HIV (WLWH). This infection leads to cervical cancer (CC) and increased mortality. Methods This study monitored HPV infection in WLWH in Rio de Janeiro, Brazil, before (T1) and after (T2) 4 years of vaccination. HPV genotyping and the presence of intraepithelial lesions were investigated at both time points. Results Among the 156 WLWH who received the quadrivalent HPV vaccine (4vHPV) at T1, 30 (19.2%) were initially found to have HPV DNA. After vaccination, only three (7%) of those who were HPV-negative at T1 tested positive for HPV. Most women who tested positive for HPV DNA at T1 had normal Pap smear results. However, this cohort also demonstrated a significant increase in cases of atypical squamous cells of uncertain significance and cervical intraepithelial neoplasia in PCR-negative HPV DNA samples at T2 ( p < .01). Conversely, women who initially tested negative for HPV DNA continued to exhibit normal Pap smear results in 2018 ( p < .01). Conclusions This study highlights the persistence of HPV in WLWH despite vaccination and underscores the importance of continued molecular and cytologic screening. The findings enhance our understanding of vaccine effectiveness in this population and emphasize the need for tailored preventive strategies.

Immunogenetics and human papillomavirus (HPV) in male genital lichen sclerosus (MGLSc)

Background The pathogenesis of male genital lichen sclerosus (MGLSc) is controversial. Incriminated factors include infection with human papillomavirus (HPV) and autoimmunity (e.g. Human Leukocyte Antigen [HLA]). To address the roles of HLA and HPV in MGLSc we studied adult Caucasian males with a clinical and histological diagnosis of MGLSc. The men in the study attended two specialised Male Genital Dermatoses Clinics between July 2011 and September 2012 and were selected and phenotyped from the clinical records. DNA was extracted from blood and paraffin-embedded biopsy sections, for HLA and HPV typing, respectively. HLA allele frequencies were compared with those derived from the UK-based Caucasian population. Eighty-eight cases of MGLSc were identified. HPV DNA was detected in 33/88 (37.5%) cases of MGLSc. HPV16 was the most prevalent type found: 11/88 (12.5%) MGLSc. No statistically significant HLA associations were established but HLA-B*35, -B*51, -C*15, -DRB1*04, -DRB1*10 (predisposition) and -DQA1*01 (protection) were revealed as alleles of interest. HPV16-associated MGLSc cases showed no statistically significant association with HLA genotype. The relationship between HPV and MGLSc suggests a passenger effect rather than a pathogenic role. HLA is not associated with MGLSc nor co-existent HPV16.

Human papillomavirus vaccine timing associated with eventual human papillomavirus diagnosis in women

Nearly all cases of cervical cancer are attributable to human papillomavirus (HPV), making it a significant women’s health issue. Though there have been advances in the prevention of HPV via vaccination, significant barriers continue to suppress vaccination rates for girls. Delaying vaccination until after sexual debut increases a woman’s chance of HPV infection, but there has been no quantification of this risk in the literature. The present study sought to address this gap via secondary data analysis with 173 female participants from the 2015–2016 National Health and Nutrition Examination Survey dataset. Results indicate that women in the sample who received the HPV vaccine after their sexual debut were 2.63 times more likely than women who receive the vaccine before their sexual debut to report an HPV diagnosis. These results have clear public and sexual health implications.

Vulval intraepithelial neoplasia in immunosuppressed women: The management outcome and recommendations from a multi-disciplinary service

Background Human papillomavirus (HPV) dependent vulval intra-epithelial neoplasia (VIN) is a precursor to vulval squamous cell carcinoma (SCC) and an important global health concern. Immunosuppression increases the concurrence of VIN as well as multicentric HPV disease. A retrospective cohort study was designed to determine the burden of VIN in immunosuppressed women and extrapolate whether immunosuppression was a risk factor for poorer treatment outcomes. Method All biopsy proven women with VIN were reviewed over a 10-year period between 2013 and 2023. Patient and disease characteristics were collected and vulval lesions were mapped in quadrants using clinical photography. Treatment outcome including recurrence after first line treatment, progression to SCC or death due to disease were included. Results 104 women were identified of whom 30% were immunosuppressed, with a higher burden of HPV disease including cervical (CIN) or anorectal (AIN) intraepithelial neoplasia and multifocal VIN. However, no difference in treatment outcome was found between the immunosuppressed and the control group. On multivariate analysis, having multifocal disease predicted worse treatment sequelae. Conclusion Immunosuppressed women need a multi-disciplinary group of specialists to manage their burden of HPV disease. Identifying multifocal and multicentric disease early is essential for improving treatment success.

Successful outcome of performing CO2 laser ablation in a middle-aged female with angiokeratoma of Fordyce

Angiokeratoma of Fordyce, a localized form of angiokeratoma, is commonly found on the scrotum but rarely affects the vulva. We have documented a case of angiokeratoma of Fordyce in a female patient. She was treated with two sessions of CO2 laser ablation, following which her lesions resolved.

The impact of concurrent HIV-infection on women with vulvar cancer: Comparison of clinical characteristics and outcome

Background HPV-related vulvar cancer is increasing in prevalence, especially in women living with HIV. Treatment of vulva cancer is based on evidence from HPV-independent cancers, which affect older women. The impact of HIV on vulvar cancer characteristics and treatment outcomes needs to be elucidated. Patients and Methods A retrospective observational study compared the clinical characteristics, treatment, and outcomes of 92 HIV-positive and 131 HIV-negative women with vulvar cancer at our institution. Using descriptive statistics, HIV-positive and negative patients were compared and Cox regression models were tested for differences in mortality and recurrence. Results HIV-positive patients were 20 years younger than HIV-negative patients ( p < 0.001). More than 50% of patients presented with advanced stage cancer, however this was independent of HIV-status. Although HIV infection was associated with poorer survival ( p = 0.022); rates of cure ( p = 0.933) and recurrence rates ( p = 0.8) were similar in HIV-positive and negative women. Conclusions Vulvar cancer occurs at a much younger age in women living with HIV. Awareness among HIV-positive women and health care providers would lead to diagnosis of vulvar cancer at an earlier stage. Treatment protocols for HPV-related vulvar cancer should not be altered due to HIV status and should take into consideration the young age of the patients.

Increasing cervical cancer screening at a non-government medical center in Lilongwe, Malawi

Malawi has the highest incidence of and mortality rate due to cervical cancer in the world. This is largely because of inadequate screening and high rates of human immunodeficiency virus (HIV) infection, which greatly increases cervical cancer risk. We describe the implementation of a quality improvement program to increase use of cervical cancer screening at a non-government medical center in Lilongwe, Malawi. The intervention, developed and launched from March to August 2017, aimed to promote education among patients and clinicians about the importance of cervical cancer screening and improve accessibility of screening information within medical records. Visual inspection with acetic acid (VIA) was used to screen for cervical cancer. Women with a positive VIA were offered treatment using thermocoagulation. The number of VIA screenings conducted in 2016 (pre-intervention), 2017 (intervention), and 2018 (post-intervention) was 125, 234 and 456, respectively. Of the 815 women screened during this period, 36 (4.4%) had a VIA-positive result and 12 (1.5%) had suspect cancer. Of the VIA-positive women, 13 (36.1%) received same-day treatment with thermocoagulation. An interrupted time series regression revealed that there was a sustained increase in monthly screenings between the pre- and post-intervention period ( β = 30.84; p = 0.006; 95% CI 9.72–51.97), suggesting that the intervention likely was effective in increasing cervical cancer screening. Our results demonstrate that focusing on developing sustainable solutions and improving system processes, without additional equipment or funding, significantly increased the number of women screened and should be considered in other settings to enhance cervical cancer prevention services.

High-risk human papillomavirus infection among women living with HIV in Latin America and the Caribbean: A systematic review and meta-analysis

We carried out a systematic review to summarize available data regarding prevalence of high-risk human papillomavirus (HR-HPV) among women living with HIV (WLHIV) in Latin America and the Caribbean (LAC). A literature search in PubMed and LILACS was conducted and supplemented with cross-referencing and grey literature. The primary outcome was prevalence of HR-HPV by age as a major determinant of HPV infection. Pooled prevalence and weighted averages were obtained. A random effects meta-analysis conducted for HPV- and HIV-associated factors. In total, 6157 women from 19 cross-sectional studies were included. Weighted prevalence of HR-HPV in WLHIV was 51.0% (95% CI 42.8–59.1, I2 = 97.4%) with a bimodal trend by age. No association between antiretroviral therapy and HR-HPV prevalence was observed, but low CD4 cell count was associated (PR 1.64, 95% CI 1.07–2.52). Although not significant, a higher HR-HPV prevalence was observed with Hybrid Capture 2 versus PCR. The high prevalence of HR-HPV among WLHIV in LAC underlines the need for improved cervical cancer prevention and early detection in this vulnerable population. Moreover, the high prevalence across age groups, and particularly in young women, deserves careful consideration for defining target populations of HPV-based screening and HPV immunization programs.

Longer duration of anti-retroviral therapy is associated with decreased risk of human papillomaviruses detection in Kenyan women living with HIV

Objective: A longitudinal study was conducted among women living with HIV in Kenya to determine if duration of anti-retroviral (ART) usage altered detection and persistence of oncogenic (high-risk) human papillomaviruses (HR-HPV). Methods: Women living with HIV without cervical dysplasia were enrolled at a cervical cancer screening clinic. Three cervical swabs, HIV viral loads, and CD4 cell counts were obtained at enrollment and at two annual visits. HPV genotyping was performed on swabs (Roche Linear Array). Linear regression models assessed effects of ART duration on HR-HPV detection and persistence. Results: Seventy-seven women, median age 38 years, completed three study visits and were included in the analysis. The mean time from HIV diagnosis to enrollment was 9.6 years (SD 3.9 years). The mean ART duration was 6.2 years (SD 3.1 years). Most women had undetectable HIV viral loads and CD4 cell counts above 500 cells/L. Each additional year of ART use reduced the likelihood of detection of HR-HPV by 10–15% and persistent detection of A9 HR-HPV by 20%. Conclusion: Among Kenyan women living with HIV, longer duration of ART use was associated with significantly reduced risk of all detection and persistent detection of HR-HPV.

Pap smear outcomes in elderly women living with HIV and HIV-negative matched controls

Objectives To describe risk factors/incidence of abnormal cervical/vaginal cytology/histology and cancer among women living with human immunodeficiency virus (WLHIV) ≥65 years compared to HIV-negative matched controls Study Design Retrospective cohort of patients who underwent Pap screening at the University of Maryland 01/2003-04/2019. Results WLHIV and HIV-negative controls ( n = 70 each) underwent 140/151 Pap tests, respectively. Among WLHIV, 29% exhibited abnormal results and were less likely than HIV-negative women with normal Paps to have had serially negative Pap tests prior to age 65 ( p = .03). In both groups, 1.4% developed cervical cancer. Abnormal Paps were more frequent in WLHIV than in HIV-negative women (31% vs 10%, p < .0001, RR:3.2, 95%CI1.9–5.4) as was HRHPV (high-risk human papillomavirus) status (43% vs 19%, p = .0233, RR:2.3, 95%CI1.2–4.6). The RR for an abnormal Pap was 2.6 (95% CI:1.1–4.2) for VL >1000 copies/mL and 0.4 (95% CI:0.2–0.7) for CD4 count of >200 cells/μL. No individual with an initially normal Pap experienced an abnormal result over a mean of 42.5 and 43.5 months in the HIV-positive and HIV-negative groups, respectively. Conclusions HIV status was associated with a higher rate of abnormal Pap/HRHPV; however, no significant difference in cervical/vaginal cancer. Elevated VL/low CD4 count were associated with greater risk for an abnormal Pap.

Anal and cervical human papillomavirus genotypes in women co-infected with human immunodeficiency virus: A systematic review

Human papillomavirus (HPV) and human immunodeficiency virus (HIV) infections are sexually transmitted. There are several HPV genotypes and clinical manifestations. Determining which genotypes circulate worldwide and/or in specific geographic areas can help with prevention programs and vaccine distribution. This systematic review aimed to investigate the most frequent anal and cervical HPV genotypes in women co-infected with HPV/HIV. The PubMed, Scientific Electronic Library Online, and Latin American and Caribbean Literature in Health Sciences databases were used to search for articles published between January 2015 and August 2021, and the included articles followed the defined selection criteria. Based on the 51 articles included, HPV16 was the most prevalent (41%) genotype, followed by HPV52 (17%) and HPV58 (14%). Based on the comparative analyses of the HIV-negative women with HPV and the HPV/HIV co-infected groups, HPV16 was frequent in both groups; HPV58, HPV31, and HPV52 were more frequent in the co-infected group; and HPV18 was more common in HIV-negative women with HPV. HPV/HIV co-infected women most frequently presented the HPV genotypes 16, 58, and 52, whereas HIV-negative women with HPV had a higher frequency of HPV16, HPV18, and HPV52 genotypes. The results indicate the importance of genotype surveillance as a strategy to improve preventive measures against HPV infection and its complications. International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42020220121.

High unmet needs for cervical cancer screening among women living with HIV in six African countries: A population-based study

Background Cisgender women living with HIV (WLWH) are disproportionately impacted by cervical cancer. Nevertheless, disparities in uptake and implementation of cervical cancer services persist in sub-Saharan Africa, where population-level estimates of screening coverage remain scarce. Methods We pooled data from nationally representative Population-based HIV Impact Assessment (PHIA) surveys conducted in Ethiopia, Malawi, Rwanda, Tanzania, Zambia, and Zimbabwe (2015–2019). After estimating the prevalence of self-reported lifetime cervical cancer screening (overall and by country), survey-weighted multivariable log-binomial regression identified socio-demographic and clinical correlates of screening uptake among WLWH aged 25–64 years. Results Overall, 6933 WLWH (mean age: 39.6 years) were included in the multi-country sample. The pooled prevalence of lifetime cervical cancer screening was 18.5% (range: 8.5% [Rwanda] to 25.3% [Zambia]). Screening uptake varied by HIV clinical status, with serostatus-aware (21.3% vs 9.0%), antiretroviral therapy-experienced (22.0% vs 10.5%), and virally suppressed (22.1% vs 11.6%) WLWH, respectively, reporting significantly ( p < 0.001) higher screening rates. Screening was especially low among WLWH aged <35 years (14.7%), with no formal education (12.1%), in the poorest households (7.9%), and residing in rural areas (14.0%). Conclusions Fewer than one-fifth of WLWH had ever screened for cervical cancer, suggesting expanded availability and access to tailored, integrated services are critically needed.

Molecular epidemiology of human papillomavirus genotypes among HIV-negative women and women living with HIV with cervical cancer in two regions in Nigeria

Background Cervical cancer (CC) is highly prevalent in Nigeria, with over 12,000 cases and 8000 deaths annually. Differences in diagnostic methods for human papillomavirus (HPV) genotypes have generated varied prevalence rates across populations. Methods We analyzed the prevalence and distribution of high-risk HPV (HR-HPV) genotypes among women with CC, comparing HIV-negative women and women living with HIV (WLWH), using data from a prospective Nigerian cohort study (2018–2022). High-throughput next-generation sequencing (NGS) of the HPV L-1 gene identified and classified genotypes. Results Among 189 women tested for HR-HPV, 74.1% (140/189) were HIV-negative, and 25.9% (49/189) were WLWH. The median age was lower for WLWH at 48 years [IQR: 41–54] compared to HIV-negative women at 60 years [IQR: 49–69] ( p < .001). The overall prevalence of HR-HPV was 64.6% (122/189; 95% CI: 57.4–71.1), with higher rates in WLWH (77.6%, 38/49) than HIV-negative women (60.0%, 84/140) ( p < .001). Among HR-HPV-positive cases, HPV16 or HPV18 accounted for the highest proportion, representing 67.2% (95% CI: 58.3–75.0). The most prevalent HR-HPV types detected were HPV16 (46.7%), HPV18 (20.5%), HPV45 (9.8%), HPV35 (6.6%), and HPV52 (5.7%). Quadrivalent and nonavalent HPV vaccines would cover 67.2% (95% CI: 58.3–75.0) and 86.1% of HR-HPV infections, respectively. Conclusion Our NGS approach findings among women with CC identified HPV types not covered by the Gardasil-4 vaccine used in Nigeria. This highlights the need for broader vaccine coverage against most HR-HPV types, regardless of HIV status, in Nigeria.

Cervical precancer and invasive cancer among women living with HIV in Latin America: A systematic review and meta-analysis

Background Data on the occurrence of cervical precancer and cancer among women living with HIV (WLHIV) in Latin American countries (LAC) are scarce and highly heterogeneous. Methods We conducted a systematic review summarizing data about the incidence/prevalence of invasive cervical cancer (CC) and high-grade precancerous lesions among WLHIV in LAC. Literature in PubMed and LILACS was searched. The primary outcome was invasive cancer incidence, and prevalence of high-grade lesions as key indicators for the WHO CC elimination strategy. Individual reports on invasive cancer incidence and prevalence of precancerous lesions were obtained, and a random effects meta-analysis was conducted for the latter. Results In total, 34,343 WLHIV from four studies reporting CC incidence in seven LAC were included, and 6079 WLHIV from 17 studies reporting prevalence of precancerous lesions in three LAC were included. CC incidence ranged between 136.0 and 398.4 per 100,000 WLHIV (with or without antiretroviral therapy). The weighted prevalence of high-grade lesions was 4.1% (95%CI: 3.8%–6.0%) with a double peak at ages 20–24 and 35–39 years. Differences in prevalence of high-grade lesions were also observed by screening approach: co-testing (11.9%), colposcopy (6.0%), cytology (4.2%), and HPV tests (3.2%). Conclusions The high incidence of invasive cancer and prevalence of high-grade lesions underline challenges to reach the WHO’s elimination goal of CC incidence below four per 100,000 among WLHIV. Moreover, the high prevalence of high-grade lesions at younger ages than in the general population is a call to accelerate the implementation of the new WHO screening recommendations in WLHIV.

Impact of STIs on cervical cancer screening: Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae in visual inspection with acetic acid (VIA) positive women in Mozambique

Background Cervical cancer, primarily from HPV, is prevalent in countries like Mozambique, with HIV individuals at higher risk. The Visual Inspection with Acetic Acid (VIA) screening method can be influenced by STIs like Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). This study examines CT and NG prevalence in HIV-positive and negative women using VIA in Mozambique’s DREAM program. Methods In this cross-sectional research conducted at a DREAM program facility in Maputo from 01/07/2021 to 31/05/2022, cervical specimens were taken from VIA-positive patients. CT/NG testing was performed using the Cobas® 4800 DNA CT/NG test. Statistical analyses focused on associations and prevalence rates, considering demographic, clinical, and exposure data. Results Among 117 women, we observed a CT prevalence of 6.8% (8/117) and an NG prevalence of 2.6%(3/117). No significant associations between CT/NG infection rates and factors such as age, HIV status, VIA results, or high-risk HPV (hrHPV) was observed. We found a 47% prevalence of hrHPV infections among participants with cervical lesions; no significant association between hrHPV and CT/NG infections was observed. Conclusion This study highlights the prevalence of CT and NG in VIA-positive women in Mozambique, emphasizing the STI burden and suggesting integration of STI screening in cervical cancer prevention strategies.

First study of genital HPV infection among women living with HIV recruited from May to September 2018 in Eastern Algeria

Background Genital HPV infection is recognized worldwide as one of the most common, if not the most common, sexually transmitted infection. Several studies have shown a higher prevalence of HPV infection in women living with HIV (WLWH). We aimed to determine the prevalence of HPV, the circulating genotypes, and its association with risk factors among Algerian WLHIV. Methods Cervical specimens were collected from 100 WLHIV. The detection of HPV infection was performed by Roche Linear Array test. Results The overall prevalence of HPV infection was determined at 32%, all including high risk HPV (HR-HPV). We found a great diversity of HR-HPV genotypes, the most common individually were HPV52, HPV16, HPV18 and HPV58, The highest prevalence was found in groups of genotype 52, 25%. HPV16 and 18 were less common (16%). Cervical cytology was abnormal in 66% (81.3% in the HPV + population), with a predominance of inflammatory lesions (75% HPV +), The most important determining risk factor for HPV infection in this series was a low CD4 T cell count <200/mm3 found in 72% of the HPV positive participants. Conclusion Our study is an initial database, to be completed by a multicenter study to determine the most frequent genotypes in Algerian WLHIV, in order to discuss the introduction of the vaccine against HPV in Algeria, especially among WLHIV.

Prevalence, incidence, and distribution of human papillomavirus types in female sex workers in Kenya

Female sex workers (FSWs) have a notably high risk of acquiring human papillomavirus (HPV) infections. Relatively few studies address the type-specific prevalence and incidence of HPV among FSWs in sub-Saharan Africa. FSWs (n = 348) attending the Korogocho clinic in Nairobi, Kenya participated from August 2009 to March 2011. HPV DNA was detected using the SPF10-LiPA25 PCR assay. Baseline prevalence of HPV infection and cervical dysplasia were calculated, stratified by HIV-serostatus. Incidence rate (IR) of infection was calculated as number of new infections from baseline over person-months among 160 HPV-negative participants with complete 12-month follow-up. Baseline HPV prevalence was 23.6% for any HPV and 20.4% for high-risk HPV (hrHPV) types. Most prevalent types were HPV52 (10.1%), HPV35 (2.3%), and HPV51 (2.3%). A quarter (24%) of participants were HIV-positive. HPV prevalence was higher in HIV-positive (32.1%) than HIV-negative (20.8%) participants. hrHPV prevalence was higher in HIV-positive (27.4%) than HIV-negative (18.2%) women. During follow-up, HPV IR was 31.4 (95% CI: 23.8–41.5) for any HPV and 24.2 (95% CI: 17.9–32.8) for hrHPV types. HPV52 had the highest IR (6.0; 95% CI: 6.5–10.3). Overall HPV and hrHPV prevalence were lower than expected, but both prevalence and incidence were higher in HIV-positive than in HIV-negative women.

Vaginal microbiota associated with oncogenic HPV in a cohort of HPV-vaccinated women living with HIV

Background Women living with HIV (WLWH) experience higher rates of human papillomavirus (HPV) infection and cervical cancer than women without HIV. Changes in the vaginal microbiome have been implicated in HPV-related disease processes such as persistence of high-risk HPV infection but this has not been well defined in a population living with HIV. Methods Four hundred and 20 girls and WLWH, age ≥9, across 14 clinical sites in Canada were enrolled to receive three doses of quadrivalent HPV vaccine for assessment of vaccine immunogenicity. Blood, cervical cytology, and cervico-vaginal swabs were collected. Cervico-vaginal samples were tested for HPV DNA and underwent microbiota sequencing. Results Principal component analysis (PCA) and hierarchical clustering generated community state types (CSTs). Relationships between taxa and CSTs with HPV infection were examined using mixed-effects logistic regressions, Poisson regressions, or generalized linear mixed-effects models, as appropriate. Three hundred and fifty-six cervico-vaginal microbiota samples from 172 women were sequenced. Human papillomavirus DNA was detected in 211 (59%) samples; 110 (31%) contained oncogenic HPV. Sixty-five samples (18%) were taken concurrently with incident oncogenic HPV infection and 56 (16%) were collected from women with concurrent persistent oncogenic HPV infection. Conclusions No significant associations between taxa, CST, or microbial diversity and HPV-related outcomes were found. However, we observed weak associations between a dysbiotic microbiome and specific species, including Gardnerella, Porphyromonas, and Prevotella species, with incident HPV infection.