The Journal of Infectious Diseases

Vaginal Microbiome Components as Correlates of Cervical Human Papillomavirus Infection

Abstract Background Interplay between vaginal microbiome and human papillomavirus (HPV) remains unclear, partly due to heterogeneity of microbiota. Methods We used data from 546 women enrolled in a cross-sectional study in 5 Brazil. We genotyped vaginal samples for HPV and sequenced V3–V4 region of 16S rRNA gene for vaginal microbiome analysis. We used stepwise logistic regression to construct 2 linear scores to predict high-risk HPV (hrHPV) positivity: one based exclusively on presence of individual bacterial taxa (microbiome-based [MB] score) and the other exclusively on participants’ sociodemographic, behavioral, and clinical (SBC) characteristics. MB score combined coefficients of 30 (of 116) species. SBC score retained 6 of 25 candidate variables. We constructed receiver operating characteristic curves for scores as hrHPV correlates and compared areas under the curve (AUC) and 95% confidence intervals (CI). Results Overall, prevalence of hrHPV was 15.8%, and 26.2% had a Lactobacillus-depleted microbiome. AUCs were 0.8022 (95% CI, .7517–.8527) for MB score and 0.7027 (95% CI, .6419–.7636) for SBC score (P = .0163). Conclusions The proposed MB score is strongly correlated with hrHPV positivity—exceeding the predictive value of behavioral variables—suggesting its potential as an indicator of infection and possible value for clinical risk stratification.

Chlamydia trachomatis, Pelvic Inflammatory Disease, and Epithelial Ovarian Cancer

Abstract Epidemiologic, clinical, molecular and translational research findings support an interrelationship between Chlamydia trachomatis, pelvic inflammatory disease (PID), and epithelial ovarian cancer (EOC). Overall, the link between C. trachomatis, PID, and EOC seems to be relatively weak, although nondifferential misclassification bias may have attenuated the results. The predominant tubal origin of EOC and the role of chronic inflammation in tumorigenesis suggest that the association is biologically plausible. Thus, C. trachomatis and PID may represent potential risk factors or risk markers for EOC. However, many steps in this chain of events are still poorly understood and need to be addressed in future studies. Research gaps include time of exposure in relation to the long-term consequences and lag time to EOC. Data of differential risk for EOC between chlamydial and nonchlamydial PID is also needed. Another major research gap has been the absence of high-performance biomarkers for C. trachomatis, PID, and EOC, as well as EOC precursors. Biomarkers for C. trachomatis and PID leading to increased risk of EOC should be developed. If the association is confirmed, C. trachomatis and PID prevention efforts may play a role in reducing the burden of EOC.

Antioxidants Associated With Oncogenic Human Papillomavirus Infection in Women

AbstractBackgroundHuman papillomavirus (HPV) infection is a major cause of cervical cancer. Studies showed the onset of HPV carcinogenesis may be induced by oxidative stress affecting the host immune system. The association between antioxidants and oncogenic HPV remains unclear. In this study, we aim to identify antioxidants associated with vaginal HPV infection in women.MethodsThe associations between the 15 antioxidants and vaginal HPV infection status (no, low-risk [LR], and high-risk [HR] HPV) were evaluated using 11 070 women who participated in the 2003–2016 National Health and Nutrition Examination Survey (NHANES).ResultsWe identified serum albumin and 4 dietary antioxidants (vitamin A, B2, E, and folate) inversely associated with HR-HPV infection. Women with a low level of albumin (≤39 g/L) have a significantly higher risk of HR-HPV (odds ratio [OR] = 1.4, P = .009 vs >44 g/L). A Nutritional Antioxidant Score (NAS) was developed based on these 4 dietary antioxidants. The women with the lowest quartile NAS had a higher chance of HR-HPV (OR = 1.3, P = .030) and LR-HPV (OR = 1.4, P = .002) compared with the women with the highest quartile NAS.ConclusionsWe identified 5 antioxidants negatively associated with vaginal HR-HPV infection in women. Our findings provide valuable insights into understanding antioxidants’ impact on HPV carcinogenesis.

How Many Human Papillomavirus Types Do We Need to Screen For?

In population-based cervical screening, human papillomavirus (HPV) types 16, 18, 31, 33, 45, and 52 are associated with >85% of HPV-associated cervical cancers. For 8 other types currently screened for, together found in <2% of these cancers, screening may be debatable.

Beyond Women's Health: Long-Term Human Papillomavirus–Related Cancer Trends in Norway

Abstract Background Understanding the total burden of human papillomavirus (HPV)–related cancers is crucial for improving prevention strategies. While organized cervical cancer (CC) screening has been implemented for many years, other HPV-related cancers lacked screening programs. Primary prevention through HPV vaccination has been implemented through national programs, initially for girls and later for boys. To analyze changes in HPV-attributable cancer incidence for both men and women, we used data from the Cancer Registry of Norway (CRN). Methods This was an observational population-based study using high-quality data from the CRN. The proportion of cancers at each site attributed to HPV was calculated based on existing literature. We estimated HPV cancer incidence rates from 1990 to 2023 and forecasted incidences until 2038 for cervical squamous cell carcinoma (SCC) and adenocarcinoma, along with other HPV-related SCCs. Results Among men, HPV-attributable cancer incidence was rising, with male oropharyngeal SCC showing the fastest increase (annual percentage change [APC], 4.5; P < .01). Overall, the incidence of HPV-attributable cancers not prevented by screening steadily increased (APC, 2.8; P < .01), surpassing CC incidence and projected to continue rising until 2038. In women, CC remains the most common HPV cancer. However, after an increasing trend since 2004, cervical SCC incidence rates decreased 6% annually from 2018 to 2023 (95% confidence interval [CI], −9.9 to −1.9; P < .01). Conclusions The burden of HPV-related cancers beyond CC is increasing in Norway, whereas CC incidence is declining. Addressing the rising total burden of HPV-attributable cancers requires additional preventive measures.

Population-Based Age-Period-Cohort Analysis of Declining Human Papillomavirus Prevalence

Abstract Background Most countries in the world have launched human papillomavirus (HPV) vaccination programs, and declining HPV prevalences are reported. We aimed to disentangle the influences of calendar time, birth cohort, and age by analyzing HPV prevalences in the population-based cervical screening program using age-period-cohort modeling. Methods All 813 882 primary HPV-based cervical screening tests from women aged 23–64 years between 2014 and 2023 in the capital region of Sweden were identified in the Swedish National Cervical Screening Registry. The odds ratio (OR) of HPV-16/18 infection was estimated comparing birth cohorts to the unvaccinated 1984-born using an age-period-cohort model. The impact of changing HPV prevalences on the number needed to screen (NNS) to detect and prevent 1 cervical cancer case was calculated. Results HPV vaccination coverage was 82%–83% among women born in 1999–2000. Before 2019, the HPV-16/18 prevalence was highest among the youngest women. During 2020–2023 the prevalence consistently decreased among the birth cohorts offered organized school-based vaccination. There was a 98% decline in HPV-16 prevalence (OR, 0.02 [95% confidence interval {CI}, .01–.04]) and a 99% decline in HPV-18 prevalence (OR, 0.01 [95% CI, .00–.04]) among the 2000-born compared to the 1984-born. The declining HPV-16/18 prevalences resulted in major increases in the NNS to detect and to prevent 1 case of cervical cancer. Conclusions The declines of HPV-16/18 were considerably larger than the vaccination coverage, suggesting herd immunity. The changing epidemiology of HPV types impacts screening needs, necessitating updated screening programs.

Impact of Multicohort Human Papillomavirus Vaccination on Cervical Cancer in Women Below 30 Years of Age: Lessons Learned From the Scandinavian Countries

Abstract In Scandinavia, human papillomavirus (HPV) vaccination programs started in 2007–2008 in Sweden and Denmark with HPV vaccination offered to multiple cohorts of young girls, while in Norway this was offered to a single cohort only. Interestingly, in Sweden and Denmark, cervical cancer incidence in young women decreased markedly from 2017 to 2018, while in Norway a steady increase was seen until 2020. As the 3 countries are very similar in other factors important for cervical cancer incidence rates, like cervical cancer screening, the observed difference is most likely due to differences in the multicohort vaccination.

Is There a Hidden Burden of Disease as a Result of Epigenetic Epithelial-to-Mesenchymal Transition Following Chlamydia trachomatis Genital Tract Infection?

Abstract Chlamydia trachomatis (CT), the most common bacterial sexually transmitted infection worldwide, has been widely researched for its involvement in many disease pathologies in the reproductive tract, including pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility. Recent findings, through the efforts to understand the pathogenesis of CT, suggest that CT can induce the process of epithelial-to-mesenchymal transition (EMT) through epigenetic changes in the epithelium of the female reproductive tract. This literature review aims to analyze the evidence for CT’s ability to promote EMT and to pinpoint the areas that merit further investigation.

Risk Factors for Non–Human Papillomavirus (HPV) Type 16/18 Cervical Infections and Associated Lesions Among HPV DNA–Negative Women Vaccinated Against HPV-16/18 in the Costa Rica Vaccine Trial

AbstractBackgroundFactors that lead human papillomavirus (HPV) infections to persist and progress to cancer are not fully understood. We evaluated co-factors for acquisition, persistence, and progression of non–HPV-16/18 infections among HPV-vaccinated women.MethodsWe analyzed 2153 women aged 18–25 years randomized to the HPV-vaccine arm of the Costa Rica HPV Vaccine Trial. Women were HPV DNA negative for all types at baseline and followed for approximately 11 years. Generalized estimating equation methods were used to account for correlated observations. Time-dependent factors evaluated were age, sexual behavior, marital status, hormonally related factors, number of full-term pregnancies (FTPs), smoking behavior, and baseline body mass index.ResultsA total of 1777 incident oncogenic non–HPV-16/18 infections were detected in 12 292 visits (average, 0.14 infections/visit). Age and sexual behavior–related variables were associated with oncogenic non–HPV-16/18 acquisition. Twenty-six percent of incident infections persisted for ≥1 year. None of the factors evaluated were statistically associated with persistence of oncogenic non–HPV-16/18 infections. Risk of progression to Cervical Intraepithelial Neoplasia grade 2 or worst (CIN2+) increased with increasing age (P for trend = .001), injectable contraceptive use (relative risk, 2.61 [95% confidence interval, 1.19–5.73] ever vs never), and increasing FTPs (P for trend = .034).ConclusionsIn a cohort of HPV-16/18–vaccinated women, age and sexual behavior variables are associated with acquisition of oncogenic non–HPV-16/18 infections; no notable factors are associated with persistence of acquired infections; and age, parity, and hormonally related exposures are associated with progression to CIN2+.

Schistosome Infection is Associated With High-Risk Human Papillomavirus Persistence, Together With Altered Cervicovaginal Microbiota

Abstract Schistosoma haematobium infection may impair female genital mucosal antiviral defense. We sought to determine whether women with S. haematobium infection had higher odds of high-risk human papillomavirus (HR-HPV) persistence, a prerequisite to cervical cancer. We also examined cervicovaginal dysbiosis, which has been linked to HR-HPV persistence and schistosome infection. In 96 Tanzanian women with baseline and 9- to 12-month follow-up samples, we performed HPV genotyping, schistosome antigen quantification, and 16S rRNA sequencing. Both S. haematobium (odds ratio: 4.7 [1.3–16.5], P = .017) and Gardnerella-dominant microbiome (P = .049) were associated with HR-HPV persistence, suggesting these factors may contribute to high cervical cancer rates in Africa.

Case-Control Study of Cervicovaginal β/γ–Human Papillomavirus Infection in Women With Human Immunodeficiency Virus and Its Relation to Incident Cervical Precancer

Abstract We studied cervicovaginal β/γ–human papillomavirus (HPV) and their relationship to cervical precancer in women with human immunodeficiency virus; having previously reported strong positive associations of β/γ-HPV with incident head and neck cancer in the general population. Case patients (n = 124) had cervical intraepithelial neoplasia (CIN) 3 or 2. Controls (n = 247) were individually matched 2:1 to case patients. Unexpectedly, multivariate analyses found strong inverse associations between β/γ-HPV and CIN-2/3 (odds ratio, 0.19 [95% confidence interval, .04–.86]; P = .03; Ptrend < .01]). This is, to our knowledge, the first study of β/γ-HPV and cervical precancer. If confirmed, a strong inverse (protective) association would be of potential clinical and biologic relevance.

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

Abstract Background In the cervicovaginal environment, human papillomavirus (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. Methods 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 were integrated with clinical and demographic surveys, immunoproteomics, and metabolomics data. Results 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. Atopobiaceae were negatively correlated with Lactobacillus and positively correlated to Sneathia, Dialister, Anaerococcus, Prevotella, and Bifidobacterium/Gardnerella. Proinflammatory cytokines (IL-1α, IL-1β, IL-12, TNF-α), immune checkpoint proteins (PD-L1, LAG3), and cancer biomarkers (CEA, MIF, TRAIL) were positively associated with Atopobiaceae-rich profiles. Prooncogenic metabolites, including 4-hydroxybutyrate and sphingosine, were also elevated in women colonized by Atopobiaceae. Conclusions 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.

Sexually Transmitted Infections and Risk of Epithelial Ovarian Cancer: Results From the Finnish Maternity Cohort

Abstract Background Sexually transmitted infections, specifically Chlamydia trachomatis (CT), may be associated with epithelial ovarian cancer (EOC) risk. The association between CT and EOC subtypes is unclear. Our aim was to investigate whether history of CT and other infections (Mycoplasma genitalium [MG], herpes simplex virus type 2 [HSV-2], and human papillomavirus [HPV]) are associated with EOC risk by histotype. Methods We measured antibodies (Abs) to CT, MG, HSV-2, and HPV-16/18 in serum samples in a nested case-control study in the Finnish Maternity Cohort (N = 484 cases 1:1 matched to controls). Logistic regression was used to calculate relative risks (RRs) and 95% confidence intervals (CIs) in seropositive versus seronegative individuals in all cases, as well as serous (n = 249), clear cell and endometrioid (n = 91), and mucinous (n = 144) EOC. Results CT seropositivity was not associated with EOC risk (eg, CT pGP3-Ab: RR, 0.92 [95% CI, .72–1.19]), regardless of disease subtype. We observed a positive association between MG seropositivity and mucinous EOC (RR, 1.66 [95% CI, 1.09–2.54]; P for heterogeneity by histotype ≤ .001), but not other subtypes. No associations were observed with seropositivity to multiple STIs. Conclusions CT infection was not associated with EOC risk, with associations observed only for MG and mucinous EOC. Mechanisms linking MG to mucinous EOC remain to be elucidated.

Cervical Intraepithelial Neoplasia Rates in British Columbia Women: A Population-Level Data Linkage Evaluation of the School-Based HPV Immunization Program

Abstract Background To understand real-world human papillomavirus (HPV) vaccine impact, continuous evaluation using population-based data is critical. We evaluated the early impact of the school-based HPV immunization program on cervical dysplasia in women in British Columbia, Canada. Methods Data linkage was performed using records from provincial cervical screening and immunization registries. Precancerous outcomes were compared between unvaccinated and HPV-vaccinated women born 1994–2005. Incidence rate, relative rate (RR), and vaccine effectiveness (VE), using unadjusted and adjusted Poisson regression of cytology (HSIL) and histopathology (CIN2, CIN3, and CIN2+) outcomes, were compared across vaccination status groups. Results Women who received a complete series of vaccine on schedule between age 9 and 14 years had an adjusted RR = 0.42 (95% confidence interval [CI], 0.31–0.57) for CIN2+ over 7 years of follow-up compared to unvaccinated women, resulting in a VE of 57.9% (95% CI, 43.2%–69.0%). Adjusted RR for HSIL was 0.53 (95% CI, .43–.64), resulting in a VE of 47.1% (95% CI, 35.6%–56.7%). Conclusion Women vaccinated against HPV have a lower incidence of cervical dysplasia compared to unvaccinated women. Immunization between 9 and 14 years of age should be encouraged. Continued program evaluation is important for measuring long-term population impact.

Validation of TypeSeq2, a Next-Generation–Based Sequencing Assay for the Detection of 46 Human Papillomavirus Genotypes, at the US National Cancer Institute and Costa Rica Laboratories

Abstract Background Cervical cancer is caused by persistent infection with carcinogenic human papillomavirus (HPV) genotypes. Prophylactic HPV vaccines are highly efficacious in preventing the acquisition of HPV infection. HPV vaccine trials and epidemiologic studies based on virologic endpoints rely on valid and reproducible measurements of HPV. We evaluated the second version of TypeSeq (TS2), a next-generation, sequencing-based assay that detects 46 HPV genotypes, in a historical phase 3 clinical trial. Methods We used 1214 stored cervical samples from women enrolled in the Costa Rica HPV Vaccine Trial with available HPV results from Short PCR Fragment 10- Line Probe Assay 25 (SPF10-LiPA25). TS2 was first validated at the National Cancer Institute (NCI) and transferred to the laboratory in Costa Rica, where we conducted a second validation study. We compared TS2 results generated at each laboratory to the SPF10-LiPA25 results. Results Overall, each laboratory demonstrated high positive agreement for most carcinogenic and noncarcinogenic genotypes between TS2 and SPF10-LiPA25. Intralaboratory comparisons revealed very high agreement in repeated testing. Interlaboratory comparisons showed high agreement for most carcinogenic and noncarcinogenic types. Overall, there were no statistically significant differences in vaccine efficacy in the according-to-protocol cohort using TS2 (either in NCI or Costa Rica) or SPF10-LiPA25 (McNemar P values >.05). Costa Rica produced similar vaccine efficacy estimates as NCI for HPV16/18, HPV31/33/45, and HPV35/39/51/52/56/58/59 as NCI (P values ≥.36). Conclusions Compared to SPF10-LiPA25, a well-established standard for HPV genotyping, TS2 demonstrated high accuracy. Inter- and intralaboratory comparisons demonstrated that TS2 is valid and reproducible. TS2 can accurately classify the presence of HPV, which is essential in HPV vaccine trials evaluating virological endpoints. Clinical Trials Registration NCT00128661.

Head-to-Head Comparison of Bi- and Nonavalent Human Papillomavirus Vaccine-Induced Antibody Responses

Abstract For head-to-head comparison of human papillomavirus (HPV) antibody levels induced by different vaccines, 25-year-old vaccine-naive women were given either the bivalent (n = 188) or the nonavalent HPV vaccine (n = 184). Six months after vaccination antibodies against pseudovirions from 17 different HPV types (HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68/73) were measured. Antibodies against HPV16/18 were higher after bivalent HPV vaccination (mean international units [IU] 1140.1 and 170.5 for HPV16 and 18, respectively) than after nonavalent vaccination (265.1 and 22.3 IUs, respectively). The bivalent vaccine commonly induced antibodies against the nonvaccine HPV types 31/33/35/45 or 58. The nonavalent vaccine induced higher antibodies against HPV6/11/31/33/45/52/58 and 35.

Quadrivalent HPV Vaccine Effectiveness Against Cervical Intraepithelial Lesion Grade 2 or Worse in Norway: A Registry-Based Study of 0.9 Million Norwegian Women

Abstract In Norway, single-cohort vaccination with quadrivalent human papillomavirus (qHPV) vaccine targeting 12-year-old girls took place in 2009–2016. In 2020, the oldest vaccinated cohort was 23 years old and had approached the age where risk of being diagnosed with cervical intraepithelial neoplasia grade 2 or worse (CIN2+) increases rapidly. The aim of this cohort study was to assess direct qHPV vaccine effectiveness (VE) against CIN2+ among Norwegian women aged 16–30 years in 2007–2020. By using population-based health registries and individual-level data on vaccination status and potential subsequent CIN2+ incidence, we found 82% qHPV VE among women vaccinated before age 17 years.

Detection of Human Papillomavirus DNA, E6/E7 Messenger RNA, and p16INK4a in Lung Cancer: A Systematic Review and Meta-analysis

Abstract Background The etiologic link between human papillomavirus (HPV) and lung cancer is still controversial. Methods PubMed and Cochrane databases were searched from inception to December 2020 to identify studies on the infection of HPV in lung cancer. We calculated the attributable proportion of HPV in lung cancer by pooling the infection of cases positive for both HPV DNA and biomarkers of carcinogenesis that may be induced by HPV (E6/E7 messenger RNA or p16INK4a). Results A total of 117 studies, comprising data of 12 616 lung cancer cases from 22 countries across 5 continents, were included. The overall HPV DNA positivity in primary lung cancer cases worldwide was 16.4% (95% confidence interval, 12.7%–20.5%). HPV DNA positivity of lung cancer varied significantly by pathological type and geographic region. Notably, the expression rate of p16INK4a is significantly higher than the positivity of HPV DNA and of HPV E6/E7 mRNA (P < .05). The estimate of HPV attributable proportion defined by expression of E6/E7 mRNA was 0 and of p16INK4a was 7.3%. Conclusions The data in this systematic review is robust enough to contradict the possible participation of HPV in lung cancer carcinogenesis. Prophylactic vaccines targeting HPV cannot have the potential to prevent lung cancer.

Detection and Clearance of Type-Specific and Phylogenetically Related Genital Human Papillomavirus Infections in Young Women in New Heterosexual Relationships

Abstract Background Understanding the natural history of human papillomavirus (HPV) infections is essential to cervical cancer prevention planning. We estimated HPV type-specific infection detection and clearance in young women. Methods The HPV Infection and Transmission among Couples through Heterosexual activity (HITCH) study is a prospective cohort of 502 college-age women who recently initiated a heterosexual relationship. We tested vaginal samples collected at 6 clinical visits over 24 months for 36 HPV types. Using rates and Kaplan-Meier analysis, we estimated time-to-event statistics with 95% confidence intervals (CIs) for detection of incident infections and clearance of incident and present-at-baseline infections (separately). We conducted analyses at the woman- and HPV-levels, with HPV types grouped by phylogenetic relatedness. Results By 24 months, we detected incident infections in 40.4% (CI, 33.4%–48.4%) of women. Incident subgenus 1 (43.4; CI, 33.6–56.4), 2 (47.1; CI, 39.9–55.5), and 3 (46.6; CI, 37.7–57.7) infections cleared at similar rates per 1000 infection-months. We observed similar homogeny in HPV-level clearance rates among present-at-baseline infections. Conclusions Our analyses provide type-specific infection natural history estimates for cervical cancer prevention planning. HPV-level analyses did not clearly indicate that high oncogenic risk subgenus 2 infections persist longer than their low oncogenic risk subgenera 1 and 3 counterparts.

Twelve-Year Trend in the Prevalence of High-Risk Human Papillomavirus Infection Among Rwandan Women Living With HIV

Abstract Background We examined the trend in prevalence of high-risk human papillomavirus (hrHPV) cervical infection among Rwandan women living with HIV (WLWH) over 12 years. Methods Prevalence of cervical hrHPV DNA was measured in 3 studies at 3 different time periods in 3 different groups of WLWH using 3 different but comparable hrHPV tests: a MY09/MY11 PCR test in 2005 (RWISA; n = 497), careHPV in 2009–2010 (HPV Demonstration; n = 1242), and Xpert HPV test in 2016–2018 (U54; n = 4734). Prevalences were adjusted for age and CD4 cell count. Results HrHPV prevalence decreased over time from 42.5% to 32.2% to 26.5% (P < .001). CD4 cell counts improved over time (Ptrend <.001) so that the percentage of WLWH with CD4 counts of ≥500 cells/μL increased from 7.7% in 2005 to 42.2% in 2009–2010 and 61.1% in 2016–2018. Thus, after adjustment for differences in CD4 counts and age, hrHPV prevalences were more similar over time: 32.6% for RWISA, 30.6% for HPV Demonstration, and 27.1% for U54 (P = .007). Conclusions Prevalence of hrHPV among WLWH has decreased over the past decade, most likely the result of improved immune reconstitution due to better HIV care and management in Rwanda.