Epidemiology of HPV-associated cancers past, present and future: towards prevention and elimination.

Cervical cancer is the first cancer deemed amenable to elimination through prevention, and thus lessons from the epidemiology and prevention of this cancer type can provide information on strategies to manage other cancers. Infection with the human papillomavirus (HPV) causes virtually all cervical cancers, and an important proportion of oropharyngeal, anal and genital cancers. Whereas 20th century prevention efforts were dominated by cytology-based screening, the present and future of HPV-associated cancer prevention relies mostly on HPV vaccination and molecular screening tests. In this Review, we provide an overview of the epidemiology of HPV-associated cancers, their disease burden, how past and contemporary preventive interventions have shaped their incidence and mortality, and the potential for elimination. We particularly focus on the cofactors that could have the greatest effect on prevention efforts, such as parity and human immunodeficiency virus infection, as well as on social determinants of health. Given that the incidence of and mortality from HPV-associated cancers remain strongly associated with the socioeconomic status of individuals and the human development index of countries, elimination efforts are unlikely to succeed unless prevention efforts focus on health equity, with a commitment to both primary and secondary prevention.

COVID-related disruptions to colorectal cancer screening, diagnosis, and treatment could increase cancer Burden in Australia and Canada: A modelling study.

COVID-19 disrupted cancer control worldwide, impacting preventative screening, diagnoses, and treatment services. This modelling study estimates the impact of disruptions on colorectal cancer cases and deaths in Canada and Australia, informed by data on screening, diagnosis, and treatment procedures. Modelling was used to estimate short- and long-term effects on colorectal cancer incidence and mortality, including ongoing impact of patient backlogs. A hypothetical mitigation strategy was simulated, with diagnostic and treatment capacities increased by 5% from 2022 to address backlogs. Colorectal cancer screening dropped by 40% in Canada and 6.3% in Australia in 2020. Significant decreases to diagnostic and treatment procedures were also observed in Australia and Canada, which were estimated to lead to additional patient wait times. These changes would lead to an estimated increase of 255 colorectal cancer cases and 1,820 colorectal cancer deaths in Canada and 234 cases and 1,186 deaths in Australia over 2020-2030; a 1.9% and 2.4% increase in mortality, respectively, vs a scenario with no screening disruption or diagnostic/treatment delays. Diagnostic and treatment capacity mitigation would avert 789 and 350 deaths in Canada and Australia, respectively. COVID-related disruptions had a significant impact on colorectal cancer screening, diagnostic, and treatment procedures in Canada and Australia. Modelling demonstrates that downstream effects on disease burden could be substantial. However, backlogs can be managed and deaths averted with even small increases to diagnostic and treatment capacity. Careful management of resources can improve patient outcomes after any temporary disruption, and these results can inform targeted approaches early detection of cancers.

Can We Make More Accurate Prognoses During Last Days of Life?

Background: Life expectancy prediction is important for end-of-life planning. Established methods (Palliative Performance Scale [PPS], Palliative Prognostic Index [PPI]) have been validated for intermediate- to long-term prognoses, but last-weeks-of-life prognosis has not been well studied. Patients admitted to a palliative care facility often have a life expectancy of less than three weeks. Reliable last-weeks-of-life prognostic tools are needed. Objective: To improve short-term survival prediction in terminally ill patients. Method: This prospective study included all patients admitted to a palliative care facility in Montreal, Canada, over one year. PPS and PPI were assessed until patients' death. Seven prognostic clinical signs of impending death (Short-Term Prognosis Signs [SPS]) were documented daily. Results: The analyses included 273 patients (76% cancer). The median survival time for a PPS ≤20% was 2.5 days, while for a PPS ≥50% it was 44.5 days, for a PPI >8 the median survival was 3.5 days and for a PPI ≤4 it was 38.5 days. Receiver operating characteristic curves showed a high accuracy in predicting survival. Median survival after the first occurrence of any SPS was below one week. Conclusions: This study demonstrated that the PPS and PPI perform well between one week and three months extending their usefulness to shorter term survival prediction. SPS items provided survival information during the last week of life. Using SPS along with PPS and PPI during the last weeks of life could enable a more precise short-term survival prediction across various end-of-life diagnoses. The translation of this research into clinical practice could lead to a better adapted treatment, the identification of a most appropriate care setting for patients, and improved communication of prognosis with patients and families.

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.

Association of naturally acquired type-specific HPV antibodies and subsequent HPV re-detection: systematic review and meta-analysis.

BACKGROUND: Understanding the role of naturally acquired (i.e., infection-induced) human papillomavirus (HPV) antibodies against reinfection is important given the high incidence of this sexually transmitted infection. However, the protective effect of naturally acquired antibodies in terms of the level of protection, duration, and differential effect by sex remains incompletely understood. We conducted a systematic review and a meta-analysis to (1) strengthen the evidence on the association between HPV antibodies acquired through past infection and subsequent type-specific HPV detection, (2) investigate the potential influence of type-specific HPV antibody levels, and (3) assess differential effects by HIV status. METHODS: We searched Embase and Medline databases to identify studies which prospectively assessed the risk of type-specific HPV detection by baseline homologous HPV serostatus among unvaccinated individuals. Random-effect models were used to pool the measures of association of naturally acquired HPV antibodies against subsequent incident detection and persistent HPV positivity. Sources of heterogeneity for each type were assessed through subgroup analyses stratified by sex, anatomical site of infection, male sexual orientation, age group, and length of follow-up period. Evidence of a dose-response relationship of the association between levels of baseline HPV antibodies and type-specific HPV detection was assessed. Finally, we pooled estimates from publications reporting associations between HPV serostatus and type-specific HPV detection by baseline HIV status. RESULTS: We identified 26 publications (16 independent studies, with 62,363 participants) reporting associations between baseline HPV serostatus and incident HPV detection, mainly for HPV-16 and HPV-18, the most detected HPV type. We found evidence of protective effects of baseline HPV seropositivity and subsequent detection of HPV DNA (0.70, 95% CI 0.61-0.80, NE = 11) and persistent HPV positivity (0.65, 95% CI 0.42-1.01, NE = 5) mainly for HPV-16 among females, but not among males, nor for HPV-18. Estimates from 8 studies suggested a negative dose-response relationship between HPV antibody level and subsequent detection among females. Finally, we did not observe any differential effect by baseline HIV status due to the limited number of studies available. CONCLUSION: We did not find evidence that naturally acquired HPV antibodies protect against subsequent HPV positivity in males and provide only modest protection among females for HPV-16. One potential limitation to the interpretation of these findings is potential misclassification biases due to different causes.

Prophylactic A-Blockers for Radiotherapy-Induced Lower Urinary Tract Symptoms in Men with Prostate Cancer: A Phase III Randomized Trial.

PURPOSE: The present phase III randomized trial assessed the efficacy of prophylactic versus therapeutic α-blockers at improving RI-LUTSs in prostate cancer patients receiving external beam radiotherapy (EBRT). METHODS: A total of 148 prostate cancer patients were randomized 1:1 to receive either prophylactic silodosin on day one of EBRT or the occurrence of RI-LUTSs. LUTSs were quantified using the international prostate symptom score (IPSS) at regular intervals during the study. The primary endpoint was the change in the IPSS from baseline to the last day of radiotherapy (RT). Secondary endpoints included changes in IPSS from baseline to 4 weeks and 12 weeks after the start of RT. RESULTS: Patient demographics, baseline IPSS, and prescribed radiation doses were balanced between arms. On the last day of RT, the mean IPSS was 14.8 (SD 7.6) in the experimental arm and 15.7 (SD 8.5) in the control arm (p = 0.40). There were no significant differences in IPSSs between the study arms in the intention-to-treat (ITT) analysis at baseline, the last day of RT, and 4 and 12 weeks post-RT. CONCLUSION: Prophylactic α-blockers were not effective at significantly reducing RI-LUTSs in prostate cancer patients treated with EBRT. Treating patients with α-blockers at the onset of RI-LUTSs will avoid unnecessary drug exposure and toxicity.

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.

End of life in haematology: quality of life predictors - retrospective cohort study.

OBJECTIVES: Haematology patients are more likely to receive high intensity care near end of life (EOL) than patients with solid malignancy. Previous authors have suggested indicators of quality EOL for haematology patients, based on a solid oncology model. We conducted a retrospective chart review with the objectives of (1) determining our performance on these quality EOL indicators, (2) describing the timing of level of intervention (LOI) discussion and palliative care (PC) consultation prior to death and (3) evaluating whether goals of therapy (GOT), PC consultation and earlier LOI discussion are predictors of quality EOL. METHODS: We identified patients who died from haematological malignancies between April 2014 and March 2016 (n=319) at four participating McGill University hospitals and performed retrospective chart reviews. RESULTS: We found that 17% of patients were administered chemotherapy less than 14 days prior to death, 20% of patients were admitted to intensive care, 14% were intubated and 5% were resuscitated less than 30 days prior to death, 18% of patients received blood transfusion less than 7 days prior to death and 67% of patients died in an acute care setting. LOI discussion and PC consultation occurred a median of 22 days (IQR 7-103) and 9 days (IQR 3-19) before death. Patients with non-curative GOT, PC consultation or discussed LOI were significantly less likely to have high intensity EOL outcomes. CONCLUSIONS: In this study, we demonstrate that LOI discussions, PC consults and physician established GOT are associated with quality EOL outcomes for patients with haematological malignancies.

Evaluation of the Use of Anticoagulotherapy in Cancer Patients in Palliative Care Residence.

Background: Several patients admitted to palliative care residences are on anticoagulotherapy (AC). Given the risks of venous thromboembolism (VTE) and bleeding, the decision to continue or stop AC on admission remains clinically challenging. Objectives: To determine the prevalence of AC use and incidence of suspected VTE and bleeding events in palliative care patients. Methods: Retrospective cohort study including all deceased patients at a Canadian palliative care residence over two years. Results: Among the 453 patients' charts reviewed (369 with cancer), 183 (40%) were on AC at admission or <30 days earlier. Only 64 (35%) continued AC, with 78% discontinuing it during their stay. Demographic parameters were similar in the AC and non-AC groups. The incidence of suspected VTE was lower in patients pursuing AC post-admission than in those who stopped: (4.6% vs. 6.7%) and, conversely, the incidence of bleeding was higher in patients on AC: (10.8% vs. 7.6%), though these differences were not statistically significant. The risk of death in cancer patients within 72 hours of suspected VTE or bleeding event was 80% and 30%, respectively. Patients on AC had a 33% reduced risk of VTE but a 44% increased risk of bleeding. Conclusion: This study provides information on the AC use in palliative care patients. In term of survivorship, it suggests a possible advantage to continue AC to prevent a symptomatic or distressing death. Given the low incidence of events, larger powered studies will be necessary to further characterize the risks/benefits of pursuing AC in patients in palliative care residences.

Site-Specific Cancer Incidence by Race and Immigration Status in Canada 2006-2015: A Population-Based Data Linkage Study.

BACKGROUND: The Canadian Cancer Registry (CCR) does not collect demographic data beyond age and sex, making it difficult to monitor health inequalities. Using data linkage, we compared site-specific cancer incidence rates by race. METHODS: The 2006 and 2011 Canadian Census Health and Environment Cohorts are population-based probabilistically linked datasets of 5.9 million respondents of the 2006 long-form census and 6.5 million respondents of the 2011 National Household Survey. Race was self-reported. Respondent data were linked with the CCR up to 2015. We calculated age-standardized incidence rate ratios (ASIRR), comparing group-specific rates to the overall population rate with bootstrapped 95% confidence intervals (CI). We used negative binomial regressions to adjust for socioeconomic variables and assess interactions with immigration status. RESULTS: The age-standardized overall cancer incidence rate was lower in almost all non-White racial groups than in the overall population, except for White and Indigenous peoples who had higher incidence rates than the overall population (ASIRRs, 1.03-1.04). Immigrants had substantially lower age-standardized overall cancer incidence rates than nonimmigrants (ASIRR, 0.83; 95% CI, 0.82-0.84). Stomach, liver, and thyroid cancers and multiple myelomas were the sites where non-White racial groups had consistently higher site-specific cancer incidence rates than the overall population. Immigration status was an important modifier of cancer risk in the interaction model. CONCLUSIONS: Differences in cancer incidence between racial groups are likely influenced by differences in lifestyles, early life exposures, and selection factors for immigration. IMPACT: Data linkage can help monitor health inequalities and assess progress in preventive interventions against cancer. See related commentary by Withrow and Gomez, p. 876.

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.

Cost-effectiveness of human papillomavirus vaccination in girls living in Latin American countries: A systematic review and meta-analysis.

BACKGROUND: Cervical cancer is a major public health problem in Latin America. Cost-effectiveness studies help stakeholders with decisions regarding human papillomavirus (HPV) vaccination programs, one of the main prevention measures. Our objective was to synthesize the results of cost-effectiveness studies of HPV vaccination in girls, to understand factors influencing cost-effectiveness in the region. METHODS: We systematically searched databases as well as repositories from conferences, Ministries of Health and Health Technology Assessment offices. Incremental cost-effectiveness ratios (ICERs) were extracted, with data converted to international dollars (I$) and inflated to 2019 values. We used the gross domestic product per capita as threshold for judging the cost-effectiveness of vaccination. We calculated the geometric mean ICER by type of vaccine, whether screening (cytology or HPV test) was used as comparator, effectiveness measure, perspective, source of funding, year of cost, and country. RESULTS: We found 24 studies. Despite the methodological differences, most studies concluded that HPV vaccination of girls in Latin American countries was either cost-saving or cost-effective. The mean ICER was I$ 3,804 for the bivalent vaccine, I$ 640 for the quadrivalent and I$ 358 for a generic HPV-16/18 vaccine. The mean ICER was lower in the studies that used HPV DNA test instead of cytology (I$ 122 vs I$ 1,841) as comparator; used the societal perspective (I$ 235 vs. I$ 1,986); were funded by non-profit sources instead of by pharmaceutical industry (I$ 421 vs. I$ 2,676); and used costs obtained prior to 2008 (I$ 365 vs I$ 1,415). We observed great variation in the mean ICERs by effectiveness measure (I$ 402 for per disability adjusted life years, I$ 461 for life year saved, and I$ 1,795 for quality adjusted life years). CONCLUSIONS: Most studies concluded that HPV vaccination of girls in Latin America countries was cost-saving or cost-effective, despite heterogeneity between models.

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.

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.

Modeling Cervical Cancer Screening Strategies With Varying Levels of Human Papillomavirus Vaccination.

Importance: Cervical cancer screening is a lifesaving intervention, with an array of approaches, including liquid-based cytology (LBC), molecular testing for human papillomavirus (HPV) infection, and combinations via parallel cotesting or sequential triage. Maximizing screening efficacy while minimizing overtreatment is vital, especially when considering how the HPV vaccine will affect the interpretation of results. Objectives: To estimate the likely outcomes of different screening modalities and to model how the increasing uptake of the HPV vaccine could affect the interpretation of screening results. Design, Setting, and Participants: This decision analytic model established a simple Markov model to compare the outcomes of different cervical cancer screening modalities on a simulated population of women (aged ≥25 years), considering different levels of HPV vaccination. Main Outcomes and Measures: The number of cases of cervical intraepithelial neoplasia (CIN) grade 2 and 3 detected and missed, the number of false positives, and the number of tests required to achieve a given level of accuracy. Positive and negative predictive values of different modalities were simulated under varying levels of HPV vaccination and therefore HPV prevalence. Results: In a simulated population of 1000 women aged 25 years and older with an HPV prevalence of 2%, HPV-based modalities outperformed LBC-based approaches, detecting 19% more true positives (HPV test sensitivity, 89.9% [95% CI, 88.6%-91.1%]; LBC test sensitivity, 75.5% [95% CI, 66.6%-82.7%]). While cotesting markedly reduced missed cases, detecting 29% more true positives than LBC alone (19.5 [95% CI, 19.3-19.7] per 1000 women screened vs 15.1 [95% CI, 13.3-16.5] per 1000 women screened), it unacceptably increased excess colposcopy referral by 94% (184.4 [95% CI, 181.8-188.0] false positives per 1000 women screened vs 95.1 [95% CI, 93.1-97.0] false positives per 1000 women screened). By contrast, triage testing with reflex screening substantially reduced false positives by a factor of approximately 10 (eg, HPV with LBC triage, 9.6 [95% CI, 9.3-10.0] per 1000 women screened). Over a lifetime of screening, reflex approaches with appropriate test intervals maximized therapeutic efficacy; as HPV vaccination rates increased, HPV-based screening approaches resulted in fewer unnecessary colposcopies than LBC approaches (HPV testing, 80% vaccine coverage: 44.1 [95% CI, 40-45.9] excess colposcopies; LBC testing, 80% vaccine coverage: 96.9 [95% CI, 96.8-97.0] excess colposcopies). Conclusions and Relevance: In this decision analytic model, the effectiveness of cervical cancer screening was dependent on the prevalence of cervical dysplasia and/or HPV infection or vaccination in a population as well as the sensitivity and specificity of various modalities. Although screening is lifesaving, overtesting or modalities inappropriate to the target population may cause significant harm, including overtreatment.

Sex- and Type-specific Genital Human Papillomavirus Transmission Rates Between Heterosexual Partners: A Bayesian Reanalysis of the HITCH Cohort.

BACKGROUND: It is unclear whether sexual transmission rates of human papillomaviruses (HPV) differ between sexes and HPV types. We estimate updated transmission rates from the final HITCH cohort study and propose an estimation method that accounts for interval-censored data and infection clearance. METHODS: We enrolled young women 18-24 years old and their male sex partners ≥18 years old in Montréal, Canada, between 2005 and 2011. We followed women over 24 months and men over 4 months. We tested genital samples with Linear Array for HPV DNA detection and genotyping. We calculated infection transmission rates between partners using a multistate Markov model via a Bayesian approach. We report the posterior median and 2.5%-97.5% percentile intervals (95% PI). RESULTS: We observed 166 type-specific incident HPV transmission events in 447 women and 402 men. The estimated median transmission rate from an HPV-positive to a negative partner was 4.2 (95% PI = 3.1 to 5.3) per 100 person-months. The transmission rate from men-to-women was 3.5 (95% PI = 2.5 to 4.7) and from women-to-men was 5.6 (95% PI = 3.8 to 7.0) per 100 person-months, corresponding to a rate ratio of 1.6 (95% PI = 1.0 to 2.5). Partners reporting always using condoms had a 0.22 (95% PI = 0.05 to 0.61) times lower HPV transmission rate than those reporting never using condoms. HPV16/18 did not have particularly high transmission rates relative to other HPV types. CONCLUSION: Our updated analysis supports previous research suggesting higher women-to-men than men-to-women HPV transmission rates and a protective effect of condoms in heterosexual partnerships. Our results also suggest that crude incidence rates underestimate HPV transmission rates due to interval-censoring. See video abstract at http://links.lww.com/EDE/B794.

Sexual Network Patterns and Their Association With Genital and Anal Human Papillomavirus Infection in Adolescent and Young Men.

PURPOSE: This study aimed to determine individual- and partner-level factors associated with human papillomavirus (HPV) infection in vaccinated and unvaccinated men. METHODS: A total of 747 men, aged 13-26 years, completed a survey of sexual behaviors and were tested for genital and perianal/anal HPV (36 types). Sexual network variables included recent and lifetime concurrency (being in more than one sexual relationship at the same time) and recent sex partner discordance (by race, ethnicity, age, and number of sexual partners). We determined individual-level and sexual network variables associated with ≥1 HPV type and HPV16/18, stratified by vaccination status, using separate multivariable logistic regression models. RESULTS: Participants' mean age was 21.2 years; 64% were positive for ≥1 HPV type and 21% for HPV16/18. Factors associated with ≥1 HPV type in unvaccinated men included recruitment site and lifetime concurrency. Factors associated with ≥1 HPV type among vaccinated men included recruitment site, Chlamydia history, main male partner, number of lifetime female partners, and no condom use with female partner. Factors associated with HPV16/18 in unvaccinated men included race and partner concurrency. Factors associated with HPV16/18 in vaccinated men included ethnicity, main male partner, and recent concurrency. CONCLUSIONS: Sexual network variables associated with HPV infection were different based on vaccination status and HPV type, suggesting risk factors for HPV infection may change as the proportion of vaccinated men increases. In addition, participant report of concurrency and not knowing whether one had practiced concurrency were consistent risk factors; clinicians should consider including concurrency in the sexual history to determine the risk of HPV.

Invited Commentary: Rethinking Cervical Cancer Elimination in Terms of Lifetime Risk Rather Than Arbitrarily Defined Age-Standardized Incidence Rates.

In their accompanying article, Vänskä et al. (Am J Epidemiol. 2021;190(4):506-514) provide us with cohort lifetime risks of cervical cancer attributable to different types of human papillomavirus in Sweden. We argue that a standardized lifetime risk such as those calculated by Vänskä et al. might be a more appropriate public health target for cervical cancer elimination than age-standardized incidence rates. Age standardization to an arbitrary standard age distribution implies an implicit value choice regarding the weight of different age groups for which we find little moral justification. Conversely, a standardized lifetime risk uses standard life expectancy as a weight, corresponding to the likelihood that cervical cancer would impact a woman and prevent her from pursuing opportunities within a standard life span. Based on the data from Vänskä et al., a standardized lifetime risk of 129-250 cervical cancers per 100,000 women born could be an aspirational alternative public health target for cervical cancer elimination as a public health problem, complementary to the World Health Organization's arbitrary draft target of 4 cervical cancers per 100,000 age-standardized woman-years.