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

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.

Immunosuppression and cancer risk in kidney transplant recipients: A retrospective cohort study.

We assessed whether contemporary immunosuppression agents were associated with cancer among kidney transplant recipients (KTR), and if this association varied by age and sex. We studied a retrospective province-wide cohort of primary KTR (1997-2016). Employing multivariable Cox models, we estimated associations of cumulative doses of prednisone, mycophenolate and tacrolimus administered over the past 10 years, lagged by 2 years, with the incidence of primary malignant neoplasms (PMN). We assessed interactions with age and sex. To assess the impact of exposure recency, we used weighted cumulative exposure (WCE) modeling. Among 1064 KTR, 108 (10.2%) developed PMN over median follow-up of 73 months (interquartile range: 32-120). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 0.96 (0.64-1.43), 1.34 (0.96-1.86), and 1.06 (0.88-1.29) were estimated for cumulative daily doses of prednisone (5 mg), mycophenolate (1000 mg), and tacrolimus (2 mg) administered continuously over the past 10 years, respectively. PMN risk associated with cumulative tacrolimus exposure was modified by age (interaction p = .035) and was more pronounced in 15-year and 30-year-old KTR (aHRs of 1.57 [1.08-2.28] and 1.31 [1.03-1.66], respectively) in comparison to older KTR. PMN risk increase associated with higher cumulative mycophenolate dose was more pronounced in females (aHR = 1.86 [1.15-3.00]) than in males (aHR = 1.16 [0.74-1.81]; interaction p = .131). WCE analyses suggested increased PMN risk the higher the mycophenolate doses taken 5-10 years ago. A trend toward increased PMN risk with long-term mycophenolate exposure, particularly in females, and more pronounced risk with long-term tacrolimus exposure in younger KTR, identify opportunities for tailored immunosuppression to mitigate cancer risk.

Scientific approaches toward improving cervical cancer elimination strategies.

At the 2023 EUROGIN workshop scientific basis for strategies to accelerate the elimination of cervical cancer and its causative agent, human papillomavirus (HPV) were reviewed. Although some countries have reached key performance indicators toward elimination (>90% of girls HPV vaccinated and >70% of women HPV screened), most are yet to reach these targets, implying a need for improved strategies. Gender-neutral vaccination, even with moderate vaccination coverage was highlighted as a strategy to achieve elimination more rapidly. It is more resilient against major disturbances in vaccination delivery, such as what happened during the coronavirus pandemic. Further, an analysis of ethical/legal issues indicated that female-restricted vaccination is problematic. Extended catch-up of vaccination with concomitant screening, and outreach to vulnerable groups were highlighted. Although birth cohorts with high coverage of HPV vaccination at school are protected against HPV, and HPVs have a very low reproductive rate in women above age 35, adult women below age 30 have inadequate direct protection. In addition to herd protection from gender-neutral vaccination, this group can be protected by offering concomitant catch-up HPV vaccination and HPV screening. Furthermore, hepatitis B vaccination experiences indicate that elimination cannot be achieved without prioritizing vulnerable/migrant populations. The long-lasting durability of vaccination-induced antibody responses suggests prolonged protection with HPV vaccines when adequately administrated. Finally, cost-effectiveness modelling suggests that high-coverage HPV vaccination in multiple population segments will be resource-saving due to reduced need for screening. In summary, the workshop found that strategically optimal deployment of vaccination will accelerate elimination of HPV and cervical cancer.

Species-level characterization of the cervicovaginal microbiota and its role in human papillomavirus-associated cervical carcinogenesis.

The cervicovaginal microbiome may contribute to human papillomavirus (HPV)-associated cervical carcinogenesis, but studies have been limited by low-resolution analysis methods. Using a high-resolution bioinformatics pipeline, we evaluated the relationship of the cervicovaginal microbiome with HPV and cervical intraepithelial neoplasia (CIN). The cervicovaginal microbiome of 186 women was characterized by sequencing 16S rRNA regions (V3-V4 and V5-V6) and annotated with the high-resolution ANCHOR pipeline. Samples were genotyped for HPV using the Roche-Cobas 4800 assay. We fitted logistic regression models using stepwise forward selection to select species (presence/absence) as correlates of CIN1+ and constructed a linear microbiome-based score using the regression coefficients. An HPV-based score was calculated from a separate logistic regression model to detect CIN1+ . Receiver operating characteristic curve analyses were performed; the area under the curve (AUC) and 95% confidence intervals (CI) were compared between scores. Overall, 66.7% of participants were HPV-positive. 77 unique species were identified: 8 using V3-V4, 48 using V5-V6, and 21 shared. Twelve species were retained via stepwise selection. The AUCs for the microbiome-, and HPV-based scores were 0.7656 (95% CI 0.6885-0.8426), and 0.7529 (95% CI 0.6855-0.8204), respectively. Bacterial species may be involved in cervical carcinogenesis as the microbiome- and HPV-based scores performed similarly for CIN1+ detection.

Naturally developed HPV16 antibodies and risk of newly detected cervical HPV infection outcomes.

Little is known about the protection conferred by antibodies from natural human papillomavirus (HPV) infection. Our objective was to evaluate the association between HPV16 seroreactivity and HPV16 redetection, newly detected HPV infections, and loss of HPV DNA detection during follow-up. We analyzed data from 2462 unvaccinated Brazilian women. HPV16 IgG and neutralizing antibodies at baseline were assessed by enzyme-linked immunosorbent assay (n = 1975) and by the pseudovirus-based papillomavirus neutralization assay (n = 487). HPV detection, genotyping, and viral load were assessed by PCR-based methods. The associations were analyzed by Cox proportional hazards models. We observed a positive association between HPV16 IgG seroreactivity and redetection of HPV16 infections. Age-adjusted hazard ratios (HR) with 95% confidence intervals (CI) ranged from 2.45 (1.04-5.74) to 5.10 (1.37-19.00). Positive associations were also observed between HPV16 IgG antibodies and (1) newly detected HPV infections by genotypes unrelated to HPV16 (age-adjusted HR [95% CI] = 1.32 [1.08-1.2]) and (2) loss of detection of HPV infections by genotypes unrelated to HPV16 (age-adjusted HR [95% CI] = 1.24 [1.03-1.50]). Naturally developed HPV16 antibodies do not prevent recurrent HPV infections. Overall HPV16 IgG and neutralizing antibodies seem to be serological markers for latent or past infections.

Impact of a carrageenan gel on viral load of genital human papillomavirus infections in sexually active women: Findings from the Carrageenan-gel Against Transmission of Cervical Human papillomavirus (CATCH) trial.

Previous research has shown that women's use of a carrageenan gel reduces the risk of acquiring genital human papillomavirus (HPV) infections but does not help to clear existing ones. Although gel use may not result in complete clearance, it may decrease the viral load of HPV infections. We tested this hypothesis in the Carrageenan-gel Against Transmission of Cervical Human papillomavirus (CATCH) randomized controlled trial. Participants of the CATCH study were selected for viral load testing if they had completed the first four study visits and tested positive for HPV42 or HPV51 in at least one of these visits. HPV42 and HPV51 were chosen as they were among the most abundant low- and high-risk types, respectively, in the study sample. We measured viral load with a type-specific real-time polymerase chain reaction. Results were displayed using summary statistics. Of 461 enrolled participants, 39 were included in the HPV42 analysis set and 56 in the HPV51 analysis set. The median time between visits 1 and 4 was 3.7 months. The viral load (copies/cell) of HPV42 ranged from <0.001 to 13 434.1, and that of HPV51 from <0.001 to 967.1. The net median change in HPV42 viral load over all four visits was -1.04 copies/cell in the carrageenan and -147 copies/cell in the placebo arm (Wilcoxon rank sum test, p = 0.26). There was no net median change in HPV51 viral load over all four visits in either arm (p = 0.45). The use of a carrageenan-based gel is unlikely to reduce the viral load of HPVs 42 or 51.

Use of a carrageenan-based gel had no impact on anal HPVs 16 and 18 viral loads in gay, bisexual, and other men who have sex with men.

The Lubricant Investigation in Men to Inhibit Transmission of human papillomavirus (HPV) Infection randomized control trial in gay, bisexual, and other men who have sex with men (gbMSM) found that carrageenan use neither reduced acquisition of anal HPV infections nor influenced infection clearance. To investigate carrageenan's lack of protective effect, we compared the change in anal HPV16 and HPV18 viral loads following carrageenan use against placebo. We restricted our analysis to participants who completed the first four study visits and had a valid baseline sample (n = 161, 54 HIV-positive). Samples were tested for HPV detection using the linear array PCR assay. HPV16- and/or HPV18-positive samples were tested for viral load using real-time PCR. For participants who tested HPV16- (n = 29) or HPV18-positive (n = 10) at least once across visits 1-4, we compared the change in type-specific viral load between study arms using the Mann-Whitney U test. Although the median net change in HPV16 and HPV18 viral loads across visits 1-4 was higher in the treatment than placebo arm (HPV16: 0.68 vs. 0.18 copies/cell, p = 0.60; HPV18: 18.32 vs. 10.12 copies/cell, p = 0.52), these differences were not statistically significant. Results were similar by HIV status. Carrageenan use did not impact anal HPV16 or HPV18 viral loads, which may further explain its lack of protective effect in gbMSM.

Safety of carrageenan-based gels as preventive microbicides: a narrative review.

BACKGROUND: Carrageenan-containing gels researched for the prevention of sexually transmitted infections (STIs) have shown promising results for human papillomavirus prevention in women, but not in men. We conducted a narrative review to assess the safety of these gels for genital use. METHODS: We searched PubMed using MeSH terms and keywords on 5 November 2023. Title/abstract of articles were screened to identify relevant ones. Full-text screening determined eligibility: empirical study evaluating safety of carrageenan-containing gel(s) for genital use. RESULTS: Of the 125 identified records, 15 were eligible, comprising 14 (10 randomised controlled trials and 4 cohorts) unique study populations. Studies included women only (n=11), men only (n=1) or both (n=3); number of participants ranged from 4 to 6202. Safety was assessed for vaginal (n=13), penile (n=3) and anal use (n=2). Most studies assessed safety of Carraguard (53%), followed by Divine9 (14%), and one each of iota-carrageenan gel, lambda-carrageenan gel, Carvir, PC-6500 (griffithsin and carrageenan) and PC-1005 (MIV-150/zinc acetate/carrageenan). Safety assessment relied on self-report (80.0%), testing for STIs (53.3%), investigator-identified genital findings (93.3%) and/or testing for changes in genital flora (60.0%). Adverse events (AEs) were described by investigators as mostly mild, (mostly) comparable between groups, not observed and/or not significant for vaginal and penile use. Only one study, assessing anal use of carrageenan, reported a significantly higher proportion of AEs in the carrageenan compared with placebo group. CONCLUSIONS: Carrageenan-based gels are generally well tolerated for vaginal and penile, but not anal use. Studies on carrageenan gel's safety for anal use are scarce.

Human Papillomavirus Intermittence and Risk Factors Associated With First Detections and Redetections in the Ludwig-McGill Cohort Study of Adult Women.

BACKGROUND: We assessed the incidence and risk factors for first detection and redetection with the same human papillomavirus (HPV) genotype, and prevalence of cytological lesions during HPV redetections. METHODS: The Ludwig-McGill cohort study followed women aged 18-60 years from São Paulo, Brazil in 1993-1997 for up to 10 years. Women provided cervical samples for cytology testing and HPV DNA testing at each visit. A redetection was defined as a recurring genotype-specific HPV positive result after 1 or more intervening negative visits. Predictors of genotype-specific redetection were assessed using adjusted hazard ratios (aHR) with Cox regression modeling. RESULTS: In total, 2184 women contributed 2368 incident HPV genotype-specific first detections and 308 genotype-specific redetections over a median follow-up of 6.5 years. The cumulative incidence of redetection with the same genotype was 6.6% at 1 year and 14.8% at 5 years after the loss of positivity of the first detection. Neither age (aHR 0.90; 95% confidence interval [CI], .54-1.47 for ≥45 years vs < 25 years) nor new sexual partner acquisition (aHR 0.98; 95% CI, .70-1.35) were statistically associated with genotype-specific redetection. High-grade squamous intraepithelial lesion prevalence was similar during first HPV detections (2.9%) and redetection (3.2%). CONCLUSIONS: Our findings suggest many HPV redetections were likely reactivations of latent recurring infections.

Efficacy of a Carrageenan Gel in Increasing Clearance of Anal Human Papillomavirus Infections in Men: Interim Analysis of a Double-Blind, Randomized Controlled Trial.

Preclinical studies have demonstrated carrageenan's anti-human papillomavirus (HPV) activity. We assessed efficacy of a carrageenan-based gel compared to a placebo gel in increasing the clearance of anal HPV infections among gay, bisexual, and other men who have sex with men (gbMSM). Of 255 enrolled gbMSM, 134 were HPV positive at baseline and had valid HPV results for ≥2 visits. Carrageenan did not differ from placebo in clearing all baseline infections (hazard ratio, 0.84 [95% confidence interval, .31-2.27]), based on having 2 consecutive HPV-negative visits following at least 1 HPV-positive visit. There were no remarkable differences for analyses at the HPV type level or by human immunodeficiency virus status. CLINICAL TRIALS REGISTRATION: NCT02354144.

Serologic Response to Human Papillomavirus Genotypes Among Unvaccinated Women: Findings From the HITCH Cohort Study.

BACKGROUND: Humoral immune responses may be critical for preventing, controlling, and/or eliminating human papillomavirus (HPV) infection. We analyzed humoral response to natural HPV infection considering phylogenetic relatedness among unvaccinated women. METHODS: We included 399 young women attending university/college in Montreal, Canada who were participants of the HITCH cohort. Participants provided blood samples at baseline and 5 follow-up visits. Antibody response to bacterially expressed L1 and E6 glutathione S-transferase (GST) fusion proteins, and virus-like particles (VLP-L1) of Alphapapillomavirus types were measured using multiplex serology. We assessed correlations and associations between HPV types at baseline using Pearson correlation coefficients (r) and univariable linear regressions. RESULTS: At baseline, > 40% were seropositive for GST-L1 antibodies of at least 1 HPV type. Strong correlations between GST-L1 were observed for α9 HPV types: 58-52 (r = 0.86), 58-33 (r = 0.75), 33-52 (r = 0.72), and between GST-E6: 52-11 (r = 0.84), 52-18 (r = 0.79), 58-33 (r = 0.78), 35-11 (r = 0.76). HPV16 VLP-L1 moderately explained variability in HPV16 GST-L1 (regression coefficient [b] = 0.38, R2 = 43.1%), and HPV45 GST-L1 in HPV18 GST-L1 (b = 0.68, R2 = 42.8%). GST-E6 antibodies accounted for a low to moderate proportion of variability in HPV16 and HPV18 GST-E6 (R2 = 6.4%-62.2%). CONCLUSIONS: Associations between naturally induced HPV-specific antibodies depend on phylogenetic relatedness.

Differences in site-specific cancer incidence by individual- and area-level income in Canada from 2006 to 2015.

Income, a component of socioeconomic status, influences cancer risk as a social determinant of health. We evaluated the independent associations between individual- and area-level income and site-specific cancer incidence in Canada. We used data from the 2006 and 2011 Canadian Census Health and Environment Cohorts, which are probabilistically linked datasets constituted by 5.9 million and 6.5 million respondents of the 2006 Canadian long-form census and 2011 National Household Survey, respectively. Individuals were linked to the Canadian Cancer Registry through 2015. Individual-level income was derived using after-tax household income adjusted for household size. Annual tax return postal codes were used to assign area-level income quintiles to individuals for each year of follow-up. We calculated age-standardized incidence rates (ASIR) and rate ratios for cancers overall and by site. We conducted multivariable negative binomial regression to adjust these rates for other demographic and socioeconomic variables. Individuals of lower individual- and area-level income had higher ASIRs compared to those in the wealthiest income quintile for head and neck, oropharyngeal, esophageal, stomach, colorectal, anal, liver, pancreas, lung, cervical and kidney and renal pelvis cancers. Conversely, individuals of wealthier individual- and area-level income had higher ASIRs for melanoma, leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, breast, uterine, prostate and testicular cancers. Most differences in site-specific incidence by income quintile remained after adjustment. Although Canada's publicly funded healthcare system provides universal coverage, inequalities in cancer incidence persist across individual- and area-level income gradients. Our estimates suggest that individual- and area-level income affect cancer incidence through independent mechanisms.

Prevalence of cervical human papillomavirus in Mexico, 2010-2017: analysis of 2.7 million women.

PURPOSE: Prevalence of cervical high-risk human papillomavirus (hrHPV) infection varies greatly. Data on distribution of hrHPV infection constitute important evidence for decision-making when implementing HPV testing into cervical cancer screening programs. We estimate the prevalence of cervical hrHPV infection in a large sample of women in a middle-income country and explore variation by age, community marginalization and region in women using public cervical cancer screening services. METHODS: Records covering 2010-2017 from a registry of hrHPV test results (Hybrid Capture 2 and polymerase chain reaction) in 2,737,022 women 35-64 years were analyzed. In this observational study, 32 states were categorized into five geographical regions and classified by degree of marginalization. We stratified by test type and estimated crude and adjusted prevalence and rate ratios and used Poisson models and joinpoint regression analysis. RESULTS: Prevalence was higher in women 35-39 years, at 10.4% (95% CI 10.3-10.5) and women 60-64 years, at 10.1% (95% CI 10.0-10.3). Prevalence was higher in the southeast, at 10.5% (95% CI 10.4-10.6). Women living in less marginalized areas had a significantly higher prevalence, at 10.3% (95% CI 10.2-10.4) compared to those in highly marginalized areas, at 8.7% (95% CI 8.5-8.7). HPV16 infection was detected in 0.92% (2,293/23,854) of women and HPV18 infection was detected in 0.39% (978/23,854) of women. CONCLUSION: Understanding the distribution of HPV prevalence has value as evidence for developing policy in order to improve cervical cancer screening strategies. These results will constitute evidence to allow decision makers to better choose where to focus those resources that they do have.

Betapapillomavirus natural history and co-detection with alphapapillomavirus in cervical samples of adult women.

Human papillomaviruses (HPV) of the genus Betapapillomavirus can infect both cutaneous and mucosal sites, but research on their natural history at mucosal sites remains scarce. We examined the risk factors and co-detection patterns of HPVs of the Betapapillomavirus and Alphapapillomavirus genera in cervical samples of the Ludwig-McGill cohort study. We assessed a subset of 505 women from the Ludwig-McGill cohort study from São Paulo, Brazil. Cervical samples over the first year of follow-up were tested for DNA of over 40 alphapapillomavirus types and 43 betapapillomavirus types using a type-specific multiplex genotyping polymerase chain reaction assay. We assessed the risk factors for prevalent and incident betapapillomavirus type detection, and whether types were detected more frequently together than expected assuming independence using permutation tests, logistic regression, and Cox regression. We observed significant within-genus clustering but not cross-genus clustering. Multiple betapapillomavirus types were co-detected in the same sample 2.24 (95% confidence interval [CI]: 1.65-3.29) times more frequently than expected. Conversely, co-detections of alphapapillomavirus and betapapillomavirus types in the same sample occurred only 0.64 (95% CI: 0.51-0.83) times as often as expected under independence. In prospective analyses, positivity to one HPV genus was associated with a nonsignificant lower incidence of detection of types in the other genus. Lifetime number of sex partners and new sex partner acquisition were associated with lower risks of prevalent and incident betapapillomavirus detection. Betapapillomaviruses are commonly found in the cervicovaginal tract. Results suggest potentially different mechanisms of transmission for betapapillomavirus genital infections other than vaginal sex.

A synthesis of evidence for cancer-specific screening interventions: A Preventive Medicine Golden Jubilee Review.

The goal of cancer screening guidelines is to inform health practitioners to practice evidence-based cancer prevention. Cancer screening aims to detect treatable precancerous lesions or early-stage disease to enable actions aimed at decreasing morbidity and mortality. Continuous assessment of the available evidence for or against screening interventions by various organizations often results in conflicting recommendations and create challenges for providers and policymakers. Here we have summarized the current cancer screening recommendations by five leading organizations in North America and Europe: the National Cancer Institute's Physician Data Query (PDQ), the U.S. Preventive Services Task Force (USPSTF), the Canadian Task Force on Preventive Health Care (CTFPHC), the Cochrane Database of Systematic Reviews (CDSR), and the UK National Screening Committee for the National Health Service (UK NSC). All organizations assess evidence based on strength, quality, and quantity, and recommendations are similar although with differences with respect to screening start and stop ages. Recommendations are consistent for colorectal cancer screening with fecal occult blood test or fecal immunochemical test, cervical cancer screening with Pap-test, HPV-test, or co-testing, and breast cancer screening with mammography. However, guidelines vary with respect to age to start and end screening and testing frequency. Tests that have proven to be inefficient or whose use is capable of causing harm are routinely recommended against. Continuous review of screening guidelines is necessary to evaluate the many promising screening tests currently under investigation.

Role of Human Leukocyte Antigen Allele Sharing in Human Papillomavirus Infection Transmission Among Heterosexual Couples: Findings From the HITCH Cohort Study.

BACKGROUND: Human leukocyte antigen (HLA) polymorphism influences innate and adaptive immune responses. Among heterosexual couples in the HPV Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) cohort study, we examined whether allele sharing in a couple predicted the partners' infections with the same human papillomavirus (HPV) type. METHODS: We tested genital samples from 271 couples for 36 HPV genotypes by polymerase chain reaction. We used direct DNA sequencing to type HLA-B07, -DRB1, -DQB1 and -G. Generalized estimating equations were used to examine the associations between the extent of allele sharing and HPV type concordance in which at least 1 of the partners was HPV positive. RESULTS: We identified 106 different HLA alleles. The most common HLA alleles among couples were G*01:01:01 (95.6%), G*01:01:02 (60.1%), DQB1*03:01 (57.2%), and DRB1*07:01 (46.9%). Allele sharing was as follows: 19.6% shared none, 43.2% shared 1 only, 25.1% shared 2, and 12.5% shared 3-5. Irrespective of HLA class, grouped or in combination, the extent of allele sharing was not a significant predictor of type-specific HPV concordance in a couple (odds ratio, 1.1 [95% confidence interval, .5-2.1], for 3-5 vs none). CONCLUSIONS: We found no evidence that the extent of HLA allele concordance influences the likelihood of HPV transmission in newly formed heterosexual couples.

Male Circumcision and Genital Human Papillomavirus (HPV) Infection in Males and Their Female Sexual Partners: Findings From the HPV Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) Cohort Study.

BACKGROUND: Previous studies examining the association between male circumcision (MC) and human papillomavirus (HPV) infections have reported inconsistent results. We used data from the HPV Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) cohort study to examine the association between MC and HPV infections in males and their female sexual partners. METHODS: We enrolled monogamous couples in a longitudinal study between 2005 and 2011 in Montreal, Canada. We used logistic and Poisson regression models with propensity score adjustment to estimate odds ratios (ORs) and rate ratios for the association between MC and the prevalence, transmission, and clearance of HPV infections. RESULTS: Four hundred thirteen couples were included in our study. The prevalence OR for the association between MC and baseline infections was 0.81 (95% confidence interval [CI], .56-1.16) in males and 1.05 (95% CI, .75-1.46) in females. The incidence rate ratio for infection transmission was 0.59 (95% CI, .16-2.20) for male-to-female transmission and 0.77 (95% CI, .37-1.60) for female-to-male transmission. The clearance rate ratio for clearance of infections was 0.81 (95% CI, .52-1.24). CONCLUSIONS: We found little evidence of an association between MC and HPV infection prevalence, transmission, or clearance in males and females. Further longitudinal couple-based studies are required to investigate this association.

Vaginal Microbiome Components as Correlates of Cervical Human Papillomavirus Infection.

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.

Proportion of Incident Genital Human Papillomavirus Detections not Attributable to Transmission and Potentially Attributable to Latent Infections: Implications for Cervical Cancer Screening.

BACKGROUND: Infections with human papillomaviruses (HPVs) may enter a latent state, and eventually become reactivated following loss of immune control. It is unclear what proportion of incident HPV detections are reactivations of previous latent infections vs new transmissions. METHODS: The HPV Infection and Transmission among Couples through Heterosexual activity (HITCH) cohort study prospectively followed young newly formed heterosexual partners recruited between 2005 and 2011 in Montréal, Canada. We calculated the fraction of incident HPV detections nonattributable to sexual transmission risk factors with a Bayesian Markov model. Results are the median (2.5th-97.5th percentiles) of the estimated posterior distribution. RESULTS: A total of 544 type-specific incident HPV detection events occurred in 849 participants; 33% of incident HPV detections occurred in participants whose HITCH partners were negative for that HPV type and who reported no other sex partners over follow-up. We estimate that 43% (38%-48%) of all incident HPV detections in this population were not attributable to recent sexual transmission and might be potentially reactivation of latent infections. CONCLUSIONS: A positive HPV test result in many cases may be a reactivated past infection, rather than a new infection from recent sexual behaviors or partner infidelity. The potential for reactivation of latent infections in previously HPV-negative women should be considered in the context of cervical cancer screening.

Predicted long-term impact of COVID-19 pandemic-related care delays on cancer mortality in Canada.

The COVID-19 pandemic has affected cancer care worldwide. This study aimed to estimate the long-term impacts of cancer care disruptions on cancer mortality in Canada using a microsimulation model. The model simulates cancer incidence and survival using cancer incidence, stage at diagnosis and survival data from the Canadian Cancer Registry. We modeled reported declines in cancer diagnoses and treatments recorded in provincial administrative datasets in March 2020 to June 2021. Based on the literature, we assumed that diagnostic and treatment delays lead to a 6% higher rate of cancer death per 4-week delay. After June 2021, we assessed scenarios where cancer treatment capacity returned to prepandemic levels, or to 10% higher or lower than prepandemic levels. Results are the median predictions of 10 stochastic simulations. The model predicts that cancer care disruptions during the COVID-19 pandemic could lead to 21 247 (2.0%) more cancer deaths in Canada in 2020 to 2030, assuming treatment capacity is recovered to 2019 prepandemic levels in 2021. This represents 355 172 life years lost expected due to pandemic-related diagnostic and treatment delays. The largest number of expected excess cancer deaths was predicted for breast, lung and colorectal cancers, and in the provinces of Ontario, Québec and British Columbia. Diagnostic and treatment capacity in 2021 onward highly influenced the number of cancer deaths over the next decade. Cancer care disruptions during the COVID-19 pandemic could lead to significant life loss; however, most of these could be mitigated by increasing diagnostic and treatment capacity in the short-term to address the service backlog.