Performance of urine samples compared to cervical samples for detection of precancer lesions among HPV-positive women attending colposcopy clinic in Mexico City.

BACKGROUND: High-risk human papillomavirus (hrHPV) detection in self-collected urine samples (SeCUS) may be a promising alternative for cervical cancer screening because of its greater acceptability, as long as it can offer comparable sensitivity to clinician-collected cervical samples (CCoS) for detecting precancer lesions. OBJECTIVE: To evaluate the performance of the SeCUS compared to that of the CCoS for cervical intraepithelial neoplasia grade 3 (CIN3) detection among hrHPV-positive women receiving colposcopy in Mexico City using different specific extended HPV typing procedures: HPV16/18, HPV16/18/35/39/68 or HPV16/18/35/39/68/31. METHODS: From March 2017 to August 2018, 4,158 female users of the cervical cancer screening program at Tlalpan Sanitary Jurisdiction in Mexico City were invited to participate in the FRIDA-Tlalpan study. All participants provided ≥ 30 mL of SeCUS, and then a CCoS was obtained with Cervex-Brush®, which was used for hrHPV typing. Participants who tested positive for hrHPV in CCoS were referred for colposcopy for diagnostic confirmation, and all SeCUS of these women were also tested for hrHPV typing. RESULTS: In total, 561 hrHPV-positive women were identified by CCoS via colposcopy, and 82.2% of the SeCUS of these women were also hrHPV positive. From both CCoS and SeCUS, 7 cases of CIN3 were detected. Considering HPV16/18 typing, CCoS and SeCUS detected 4 cases of CIN3, but after HPV16/18/35/39/68/31 extension typing, both CCoS and SeCUS detected all 7 of the CIN3 cases among the hrHPV-positive women. CONCLUSIONS: Using extended hrHPV typing based on HPV16/18/35/39/68/31, our results suggest that the performance of SeCUS may be equivalent to that of CCoS for detecting CIN3 lesions. Although our results are inconclusive, they support the hypothesis that SeCUS may be an attractive alternative worthy of further research.

Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections in Tlaxcala, Mexico.

Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are widely recognised as two prevalent sexually transmitted infections that can have detrimental effects on women's reproductive health. Previous research has concentrated on studying high-risk populations, resulting in limited epidemiological data regarding the general population. Therefore, the objective of this study was to estimate the prevalence of CT and NG among women attending public primary health care in Tlaxcala, Mexico. The study sample included 2,396 women already participating in the cervical cancer screening programme, from July to November 2014. After obtaining informed consent, the CT and NG tests were conducted on cervical samples, using a nucleic acid amplification test. We estimate the prevalence with 95% confidence intervals (CIs). Women who tested positive were promptly notified and provided with appropriate treatment. In our study population, CT and NG prevalences were 3.2 (95% CI: 2.6-4.0) and 0.01 (95% CI: 0.01-0.03), respectively. CT prevalence was higher in younger women (age < 40), although the results indicate a low prevalence; due to the potentially significant impact of CT and NG on women's health, we require adequate surveillance, and guaranteeing rapid referral to the correct treatment is a priority for the control of these diseases.

Clinical Performance of hrHPV Primary Screening Using Vaginal versus Cervical Samples to Detect High-grade Intraepithelial Lesions.

High-risk human papillomavirus (hrHPV) testing is now the most recommended primary method for cervical cancer screening worldwide. Clinician-collected cervical sampling continues to be the main sampling method, but hrHPV vaginal self-sampling is an appealing alternative because of its greater acceptability and potentially higher cost-effectiveness. This study aimed to determine whether hrHPV vaginal self-sampling is comparable with clinician-collected cervical sampling for detecting histologically confirmed high-grade cervical intraepithelial neoplasia (CIN2/3) as part of a cervical cancer screening program in Mexico. We analyzed data from 5,856 women screened during a hrHPV-based screening study. Clinical performance and diagnostic efficiency metrics were estimated for the two sampling methods for the CIN3 and CIN2+ endpoints, using three triage strategies: HPV16/18 genotyping, HPV16/18/33/58 extended genotyping, and HPV16/18/31/33/58 extended genotyping. hrHPV-positivity was found in 801 (13.7%) cervical and 897 (15.3%) vaginal samples. All women with hrHPV-positive samples were referred to colposcopy, which detected 17 total CIN3 cases before considering retrospective triage strategies. Using the HPV16/18/31/33/58 extended genotyping strategy, 245 women had hrHPV-positive cervical samples and 269 had hrHPV-positive vaginal samples. Ten CIN3 cases were detected each among women with hrHPV-positive cervical samples and among those with hrHPV-positive vaginal samples when using this strategy, with no significant differences in sensitivity and specificity observed. We observe that self- and clinician-collected sampling methods are comparable for detecting CIN3 and CIN2+ regardless of the triage strategy used. These findings can help public health officials to develop more cost-effective cervical cancer screening programs that maximize participation. PREVENTION RELEVANCE: We found that hrHPV vaginal self-sampling is comparable with hrHPV clinician cervical sampling when using any triage strategy to refer women to colposcopy, so self-sampling is a viable cervical screening method. Therefore, policymakers should consider incorporating self-sampling into cervical screening programs to increase screening coverage and reduce cervical cancer burden. See related Spotlight, p. 649.

Latin American and the Caribbean Code Against Cancer 1st edition: Infections and cancer.

About 13% of all cancers around the world are associated with infectious agents, particularly in low-resource settings. The main infectious agents associated with cancer are Helicobacter pylori (H. pylori), that causes gastric cancer, human papillomavirus (HPV) that causes cervical, vulvar, vaginal, penile, anal, and oropharyngeal cancer, hepatitis B and C viruses that cause liver cancer, and human immunodeficiency virus (HIV), associated with cancers of the cervix, Kaposi sarcoma (KS) and non-Hodgkin´s lymphoma. In Latin America and the Caribbean (LAC), about 150,000 cancer cases are caused annually by infections. The LAC Cancer Code Against Cancer consists of a set of 17 evidence-based and individual-level cancer prevention recommendations targeted to the general population, suited to the epidemiological, socioeconomic, and cultural conditions of the region, and tailored to the availability and accessibility of health-care systems. The recommendations with respect to infection-driven malignancies include testing and treating for H. pylori in the context of specific public health programs, vaccination against HPV and Hepatitis B Virus (HBV) and detection and treatment of chronic infections with HBV, Hepatitis C virus (HCV) and HIV, in addition to the promotion of safe sex and use of condoms to prevent sexually transmitted infections (STI). Countries, policy makers, health care systems and individuals should consider the adoption of these recommendations to help reduce the incidence and mortality of infection-related cancers in LAC, to improve quality of life of individuals and reduce the costs of cancer care in the region.

Prevalence and development of a risk score for oral human papillomavirus infection in men who have sex with men in Mexico.

BACKGROUND: Men who have sex with men (MSM) are at high risk for oral human papillomavirus (HPV infection). There are no specific screening guidelines to facilitate the identification of people at risk for oral HPV infection. We aimed to estimate the prevalence of oral high-risk HPV and create a risk score to identify MSM at higher risk for prevalent oral HPV. METHODS: We collected baseline data from a clinical trial from a subsample of 500 MSM attending sexually transmitted disease treatment clinics; they provided an oral gargle sample for high-risk HPV detection. We calculated oral high-risk HPV prevalence and 95% confidence intervals (CIs), used a logistic regression model to identify factors associated with high-risk HPV infection, and created a risk score. RESULTS: The prevalence of any oral high-risk HPV among MSM was 11.1% (95% CI: 8.6-14.2), with a higher prevalence observed among men living with HIV (14.8%). Factors independently associated with oral high-risk HPV were age ≥40 years (OR = 2.71, 95% CI: 1.28-5.73 compared to <40 years), being HIV-positive with CD4 count 200-499 (OR = 2.76, 95% CI: 1.34-5.65 compared to HIV-negative), and recent recreational use of vasodilators (poppers/sildenafil) (OR = 2.02, 95% CI: 1.02-2.97). The risk score had good discriminatory power (AUC = 0.70, 95% CI: 0.63-0.77). CONCLUSIONS: MSM have specific predictors for prevalent oral high-risk HPV, and a risk score could be used by clinicians to target men with vaccine recommendations and counseling, and identify those who could benefit from primary interventions given the available resources, or for referral to dental services for follow-up when available.

Human Papillomavirus 16 Lineage A Variants Associated With Persistent Genital Infections in Men: The HPV Infection in Men (HIM) Study.

BACKGROUND: Human papillomavirus (HPV) 16 non-A lineage variants have higher carcinogenic potential for cervical cancer. HPV-16 variants natural history among males is not established. We evaluated HPV-16 variants prevalence and persistence in the external genitalia of men enrolled in the prospective HPV Infection in Men (HIM) Study. METHODS: The HIM Study included men from the United States, Brazil, and Mexico. HPV-16 variants were distinguished using polymerase chain reaction sequencing. The prevalence of HPV-16 variants was assessed, and associations with infection persistence were estimated. RESULTS: We characterized the HPV-16 variants for 1700 genital swab samples from 753 men and 22 external genital lesions in 17 men. The prevalence of HPV-16 lineages differed by country and marital status (P < .001). Overall, 90.9% of participants harbored lineage A variants. The prevalence of non-A lineages was heterogenous among countries. HPV-16 lineage A variants were associated with a 2.69-fold increased risk of long-term persistent infections compared with non-A lineages. All high-grade penile intraepithelial neoplasia harbored lineage A variants and occurred in the context of long-term persistent infections with the same variants. CONCLUSIONS: The prevalence and persistence of HPV-16 variants observed at the male external genitalia suggest differences in the natural history of these variants between men and women, which may be associated with intrinsic differences in the infected genital epithelia.

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.

Control of Epstein-Barr Virus (EBV) in the Oral Cavity Is Associated With Persistence of Oral Human Papillomavirus (HPV)16/18 Among Men From the HPV Infection in Men Study.

BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal cancer (OPC) incidence is increasing among men. Biomarkers that can identify oral HPV16/18 infections likely to persist, the obligate precursor for HPV-OPC, are needed. METHODS: We assessed the association between oral Epstein-Barr virus (EBV) and oral HPV16/18 persistence among 63 men in the HPV Infection in Men Study who tested positive for HPV16/18 at the baseline visit. Control of oral coinfections, including EBV, could serve as a biomarker of immune competence and the ability to control oral HPV. RESULTS: Detection of oral EBV was significantly associated with oral HPV16/18 ≥12-month persistence. CONCLUSIONS: Detection of oral EBV deserves evaluation as a biomarker for oral HPV persistence and HPV-related OPC.

Latent Class Analysis of Polysubstance Use and Sexual Risk Behaviors among Men Who Have Sex with Men Attending Sexual Health Clinics in Mexico City.

Men who have sex with men (MSM) are more likely to use drugs and other substances compared to their heterosexual peers. No studies have evaluated patterns of substance use among MSM adults in Mexico. We used latent class analysis (LCA) to identify MSM subgroups with specific substance use patterns and their associations with sexual behaviors. METHODS: Data from 1850 adult MSM were collected at HIV clinics in Mexico City between September 2018 and December 2019. The structural equation modeling approach was used to estimate a LC model to identify patterns of substance use by self-report of substance use (i.e., cigarette smoking, alcohol, and drugs). To evaluate LC membership, we included HIV status, condomless anal sex (CAS), and serosorting, while controlling for demographic variables. RESULTS: 30.3% were under the age of 22. Alcohol use in last 30 days (76.2%), binge drinking (29.2%), marijuana (29.4%), sex-drugs (23.9%), stimulants (13.7%), and depressants (6.3%). MSM reported engaging in CAS (55.9%) and serosorting (13.5%) behaviors, and 40% reported being HIV positive. LCA indicated three general categories of MSM substance users: Class 1 (49.0%), Class 2 (29.8%), and Class 3 (20.4%). Members of Class 3 were younger: 23-28 age years (aOR = 1.86) and 29-33 age years (aOR = 1.86), more educated: completed graduate studies (aOR = 1.60), had a high probability of polysubstance use and were more likely to engage in CAS and serosorting. CONCLUSIONS: Attempts to detect alcohol and problematic use of substances are needed for MSM followed by culturally competent approaches that address alcohol and drug use disorders.

The Association between Smoking and Anal Human Papillomavirus in the HPV Infection in Men Study.

BACKGROUND: Previous studies show an association between smoking and anal cancer. The objective of this study was to assess the association between smoking and anal HPV (human papillomavirus) prevalence, incidence, and persistence in men. METHODS: The HPV Infection in Men (HIM) Study is a multinational study that enrolled HIV-negative men. At baseline and follow-up visits, anal specimens were collected. HPV genotyping was assessed by linear array. Prevalence ratios (PR) were used to assess the association between smoking and anal HPV prevalence. Odds ratios (OR) were used to assess the association between smoking and anal HPV incidence and ≥12-months persistence. RESULTS: Current smokers have a higher prevalence [adjusted PR (aPR), 1.36; 95% confidence interval (CI), 1.06-1.73) and incidence [adjusted OR (aOR), 1.74; 95% CI, 1.26-2.39] and ≥12-months persistence (aOR, 1.67; 95% CI, 1.19-2.33) of any anal HPV compared with never smokers. There were no differences in the prevalence, incidence, or persistence of anal HPV between former and never smokers. Smoking status was not associated with the prevalence or persistence of anal HPV among men who have sex with men but was associated with higher incidence of HR-HPV. Among men that have sex with women (MSW), current smokers had an increased prevalence and incidence of LR-HPV compared with never smokers. CONCLUSIONS: Current smokers had a higher prevalence, persistence, and incidence of HPV compared with never smokers. Further research is needed to assess the role smoking in anal HPV persistence and progression to disease. IMPACT: Prevention initiatives should raise awareness about smoking and the risk factor of anal HPV infection and anal cancer.

Association of high-risk human papillomavirus with ocular surface squamous neoplasia: a case-control study in Mexico.

OBJECTIVE: To investigate the association of high-risk hu-man papilloma virus (HR-HPV) and other risk factors with ocular surface squamous cell neoplasia (OSSN). MATERIALS AND METHODS: We obtained DNA from 22 fresh frozen OSSN tissues and 22 pterygia as controls, we used a broad-spectrum HPV DNA amplification short PCR fragment to identify HPV infection in all specimens and then genotyped HPV by a reverse hybridization line probe assay. We also obtained demographic, sun exposure, and tobacco consump-tion information. RESULTS: HR-HPV frequency was 40.9% in the OSSN group and 4.5% in the pterygia group (p=0.009). After covariate adjustment, OSSN was associated with HR-HPV (OR=16.3, 95%CI=1.2,218.1, p=0.03) and sunburn (OR=10.8, 95%CI=1.8,86.0, p=0.02). CONCLUSIONS: Ocular surface squamous cell neoplasia is a multifactorial disease. The strong association between HR-HPV and OSSN, suggests that HR-HPV could play an etiological role in OSSN development.

Association of high-risk human papillomavirus with ocular surface squamous neoplasia: a case-control study in Mexico / Asociación del virus del papiloma humano de alto riesgo con la neoplasia escamosa de la superficie ocular: estudio de casos y controles en México

Abstract: Objective: To investigate the association of high-risk human papilloma virus (HR-HPV) and other risk factors with ocular surface squamous cell neoplasia (OSSN). Materials and methods: We obtained DNA from 22 fresh frozen OSSN tissues and 22 pterygia as controls, we used a broad-spectrum HPV DNA amplification short PCR fragment to identify HPV infection in all specimens and then genotyped HPV by a reverse hybridization line probe assay. We also obtained demographic, sun exposure, and tobacco consumption information. Results: HR-HPV frequency was 40.9% in the OSSN group and 4.5% in the pterygia group (p=0.009). After covariate adjustment, OSSN was associated with HR-HPV (OR=16.3, 95%CI=1.2,218.1, p=0.03) and sunburn (OR=10.8, 95%CI=1.8,86.0, p=0.02). Conclusions: Ocular surface squamous cell neoplasia is a multifactorial disease. The strong association between HR-HPV and OSSN, suggests that HR-HPV could play an etiological role in OSSN development.

Resumen: Objetivo: Investigar la asociación del virus del papiloma humano de alto riesgo (VPH-AR), así como de otros factores, con neoplasia escamosa de la superficie ocular (NESO). Material y métodos: Se obtuvieron 22 especímenes de tejido fresco de NESO y 22 de pterigión como controles; se utilizó una técnica molecular altamente sensible para identificar la infección por VPH en todos los especímenes, así como la genotipificación del VPH. También se obtuvo información demográfica sobre exposición a la luz solar y tabaquismo. Resultados: La frecuencia de infección por VPH-AR fue de 40.9% en el grupo de NESO y de 4.5% en el grupo control (p=0.009). Después de ajustar por covariables, NESO se asoció con el VPH-AR (OR=16.3, IC95%=1.2,218.1, p=0.03) y el eritema solar (OR=10.8, IC95%=1.8,86.0, p=0.02). Conclusiones: La neoplasia escamosa de superficie ocular en una neoplasia multifactorial. Los presentes resultados sugieren que el VPH-AR podría tener un papel etiológico en el desarrollo de NESO.

Prevalence and persistence of HPV-16 molecular variants in the anal canal of men: The HIM study.

BACKGROUND: HPV-16 causes approximately 90% of anal canal (AC) cancers worldwide. This study aimed to evaluate the prevalence and persistence of HPV-16 genetic variants in the AC of men from three different countries (Brazil, Mexico and United States) and to further identify sociodemographic and behavioral factors associated with these infections. METHODS: Participants from the multinational prospective HPV Infection in Men (HIM) Study who had at least one HPV-16 positive AC swab were included. Characterization into HPV-16 genetic variants was successfully performed by PCR-sequencing in 95.6% (217/227) samples and these were classified into HPV-16 lineages and sublineages. RESULTS: We observed higher prevalence of lineage A variants, mainly from A1 sublineage, in all countries. Non-A lineage variants were mostly detected in men from Brazil, where higher diversity of sublineage variants was detected during follow-up. Compare to men detected with Non-A HPV-16 lineage variants, men infected with lineage A reported a higher lifetime number of female sexual partners. Finally, a significantly higher prevalence of Non-A lineage variants was observed among men who have sex with men (MSM) with a transient HPV-16 AC infection (p = 0.033), but no significant differences regarding variants lineages and persistence status were observed when stratified by country, self-reported ethnicity or age. CONCLUSIONS: Our data extend previous reports which indicate that globally HPV-16 variants are unevenly distributed, and contribute further to studies of the natural history of AC HPV infections in men.

The Role of External Genital Lesions in Human Immunodeficiency Virus Seroconversion Among Men Participating in a Multinational Study.

BACKGROUND: Studies in women have shown an increased risk of human immunodeficiency virus (HIV) acquisition with prior human papilloma virus (HPV) infection; however, few studies have been conducted among men. Our objective was to assess whether HPV-related external genital lesions (EGLs) increase risk of HIV seroconversion among men. METHODS: A total of 1379 HIV-negative men aged 18 to 70 years from the United States, Mexico, and Brazil were followed for up to 7 years and underwent clinical examination for EGLs and blood draws every 6 months. Human immunodeficiency virus seroconversion was assessed in archived serum. Cox proportional hazards and marginal structural models assessed the association between EGL status and time to HIV seroconversion. RESULTS: Twenty-nine participants HIV seroconverted during follow-up. Older age was associated with a lower hazard of HIV seroconversion. We found no significant difference in the risk of HIV seroconversion between men with and without EGLs (adjusted hazard ratio, 0.94; 95% confidence interval, 0.32-2.74). Stratified analyses focusing on men that have sex with men found no association between EGLs and HIV seroconversion risk (hazards ratio, 0.63; 95% confidence interval, 0.00-1.86). CONCLUSIONS: External genital lesions were not associated with higher risk for HIV seroconversion in this multinational population, although statistical power was limited as there were few HIV seroconversions. Results may differ in populations at higher risk for HIV.

Efficacy, immunogenicity, and safety of a quadrivalent HPV vaccine in men: results of an open-label, long-term extension of a randomised, placebo-controlled, phase 3 trial.

BACKGROUND: The quadrivalent human papillomavirus (HPV) vaccine was shown to prevent infections and lesions related to HPV6, 11, 16, and 18 in a randomised, placebo-controlled study in men aged 16-26 years. We assessed the incidences of external genital warts related to HPV6 or 11, and external genital lesions and anal dysplasia related to HPV6, 11, 16, or 18, over 10 years of follow-up. METHODS: The 3-year base study was an international, multicentre, double-blind, randomised, placebo-controlled trial done at 71 sites in 18 countries. Eligible participants were heterosexual men (aged 16-23 years) or men who have sex with men (MSM; aged 16-26 years). Men who had clinically detectable anogenital warts or genital lesions at screening that were suggestive of infection with non-HPV sexually transmitted diseases, or who had a history of such findings, were excluded. Eligible participants were randomly assigned (1:1) to receive three doses of either quadrivalent HPV vaccine or placebo on day 1, month 2, and month 6, administered as a 0·5-mL injection into the deltoid muscle. The 7-year, open-label, long-term follow-up extension study was done at 46 centres in 16 countries. Participants who received one or more doses of the quadrivalent HPV vaccine in the base study were eligible for enrolment into the long-term follow-up study (early vaccination group). Placebo recipients were offered the three-dose quadrivalent HPV vaccine at the end of the base study; those who received one or more quadrivalent HPV vaccine doses were eligible for enrolment into the long-term follow-up study (catch-up vaccination group). The primary efficacy endpoints were the incidence of external genital warts related to HPV6 or 11 and the incidence of external genital lesions related to HPV6, 11, 16, or 18 in all participants and the incidence of anal intraepithelial neoplasia (including anal warts and flat lesions) or anal cancer related to HPV6, 11, 16, or 18 in MSM only. The primary efficacy analysis was done in the per-protocol population for the early vaccination group, which included participants who received all three vaccine doses, were seronegative at day 1 and PCR-negative from day 1 through month 7 of the base study for the HPV type being analysed, had no protocol violations that could affect evaluation of vaccine efficacy, and had attended at least one visit during the long-term follow-up study. For the catch-up vaccination group, efficacy was assessed in the modified intention-to-treat population, which included participants who had received at least one vaccine dose, were seronegative and PCR-negative for HPV types analysed from day 1 of the base study to the final follow-up visit before receiving the quadrivalent HPV vaccine, and had at least one long-term follow-up visit. Safety was assessed in all randomised participants who received at least one vaccine dose. This study is registered with ClinicalTrials.gov, NCT00090285. FINDINGS: Between Aug 10, 2010, and April 3, 2017, 1803 participants were enrolled in the long-term follow-up study, of whom 936 (827 heterosexual men and 109 MSM) were included in the early vaccination group and 867 (739 heterosexual men and 128 MSM) were included in the catch-up vaccination group. Participants in the early vaccination group were followed up for a median of 9·5 years (range 0·1-11·5) after receiving the third dose of the quadrivalent HPV vaccine, and participants in the catch-up vaccination group were followed up for a median of 4·7 years (0·0-6·6) after receiving the third dose. In early vaccine group participants during long-term follow-up compared with the placebo group in the base study, the incidence per 10 000 person-years of external genital warts related to HPV6 or 11 was 0·0 (95% CI 0·0-8·7) versus 137·3 (83·9-212·1), of external genital lesions related to HPV6, 11, 16, or 18 was 0·0 (0·0-7·7) versus 140·4 (89·0-210·7), and of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 in MSM only was 20·5 (0·5-114·4) versus 906·2 (553·5-1399·5). Compared with during the base study (ie, before quadrivalent HPV vaccine administration), during the long-term follow-up period, participants in the catch-up vaccination group had no new reported cases of external genital warts related to HPV6 or 11 (149·6 cases per 10 000 person-years [95% CI 101·6-212·3] vs 0 cases per 10 000 person-years [0·0-13·5]) or external genital lesions related to HPV6, 11, 16, or 18 (155·1 cases per 10 000 person-years [108·0-215·7] vs 0 cases per 10 000 person-years [0·0-10·2]), and a lower incidence of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 (886·0 cases per 10 000 person-years [583·9-1289·1] vs 101·3 cases per 10 000 person-years [32·9-236·3]). No vaccine-related serious adverse events were reported. INTERPRETATION: The quadrivalent HPV vaccine provides durable protection against anogenital disease related to HPV6, 11, 16, and 18. The results support quadrivalent HPV vaccination in men, including catch-up vaccination. FUNDING: Merck Sharp & Dohme.

Comparative performance of the human papillomavirus test and cytology for primary screening for high-grade cervical intraepithelial neoplasia at the population level.

The World Health Organization recommends high-risk human papillomavirus (hrHPV)-based screening for women 39 to 49 years, based on the greater accuracy of hrHPV-based screening for cervical cancer detection. Many cervical cancer screening programs have incorporated hrHPV testing and multiple early cervical cancer detection strategies have been evaluated, mostly under controlled conditions. However, there are few evaluations of combined hrHPV and cytology strategies post-implementation at the population level. Our study sought to estimate the relative yield of hrHPV testing compared to cervical cytology, as a primary screening test for cervical intraepithelial neoplasia grade 2+ (CIN2+), used at the population level. We analyzed screening data from Mexico's public cervical cancer prevention program from 2010 to 2015 in women 35 to 64 years. The study population consisted of two cohorts: one from a total of 2 881 962 cytology-based screening tests and another from a total of 2 004 497 hrHPV-based screening tests, which are concurrent in time. We performed a relative yield analysis using Poisson regression models to compare the effectiveness of hrHPV testing for CIN2+ with cervical cytology. A total of 4 886 459 records were analyzed, including 23 999 biopsies; 0.12% (n = 6166) had a CIN2+ histologic diagnosis. hrHPV testing with cytological triage detects twice as many CIN2+ cases as screening using cytology alone.

Metodología de la Encuesta Nacional de Salud y Nutrición 2021 / National Health and Nutrition Survey 2021 methodology

Resumen: Objetivo: Describir el diseño de la Encuesta Nacional de Salud y Nutrición 2021 (Ensanut 2021). Material y métodos: La Ensanut 2021 es una encuesta probabilística de hogares que forma parte de la serie de Ensanut Continua 2020-2024. En esta ocasión se describen el alcance, el muestreo, la medición y la organización logística. Resultados: Se planea obtener al menos 12 060 entrevistas de hogar completas a nivel nacional y 9 837 muestras para determinar seropositividad a SARS-CoV-2 a nivel nacional. Conclusiones: La Ensanut 2021 permitirá realizar inferencias regionales sobre la prevalencia de seropositividad a SARS-CoV-2 y también acumular información para realizar inferencias estatales en el año 2024.

Abstract: Objective: To describe the design of the Mexican 2021 National Health and Nutrition Survey (Ensanut 2021). Materials and methods: The Ensanut 2021 is a probabilistic household survey that is part of the continuous Ensanut 2020-2024; survey outreach, sampling, measurement and logistic organization are described. Results: It is planned to obtain at least 12 060 complete household interviews and 9 837 samples to determine SARS-CoV-2 seropositivity at the national level. Conclusions: Ensanut 2021 will allow to estimate the seroprevalence of SARS-CoV-2 antibodies at regional and national level; also, it will accumulate information to make state inferences for the year 2024.

Increases in HPV-16/18 antibody avidity and HPV-specific memory B-cell response in mid-adult aged men post-dose three of the quadrivalent HPV vaccine.

Strong quantitative and functional antibody responses to the quadrivalent human papillomavirus (HPV) vaccine were reported in mid-adult aged men, but there are limited data on the avidity of the antibody response and the memory B-cell response following vaccination. Although circulating antibodies induced by vaccination are believed to be the main mediators of protection against infection, evaluation of avidity of antibodies and memory B cell responses are critical for a better understanding of the vaccine immunogenicity mechanisms. Both the modified enzyme-linked immunosorbent assay (ELISA) and the enzyme-linked immunosorbent spot (ELISpot) assay are tools to measure the humoral and cellular immune responses post vaccination to characterize vaccine immunogenicity. The avidity of HPV-16 and HPV-18 specific IgG in the serum of mid-adult aged men (N = 126) who received three quadrivalent HPV vaccine doses was examined using a modified ELISA. HPV-16 memory B-cell responses were assessed via ELISpot at month 0 (prior to vaccination) and 1-month post-dose three of the vaccine (month 7). The quadrivalent vaccine induced an increase in HPV-16 and HPV-18 antibody avidity at month 7. HPV-18 avidity levels moderately correlated with anti-HPV-18 antibody titers, but no association was observed for HPV-16 antibody titers and avidity levels. The HPV-16-specific memory B-cell response was induced following three vaccine doses, however, no association with anti-HPV-16 antibody avidity was observed. Three doses of quadrivalent HPV vaccine increased antibody affinity maturation for HPV-16/18 and increased the frequency of anti-HPV-16 memory B-cells in mid-adult aged men.

Sequential acquisition of human papillomavirus infection between genital and oral anatomic sites in males.

Oral human papillomavirus (HPV) is associated with increasing rates of HPV-associated oropharyngeal cancer (OPC) in men. Sequential infection from one site to another has been demonstrated at the cervix and anus. Thus, risk of an oral HPV infection after a genital infection of the same type in the HPV infection in men study was investigated. Samples from 3140 men enrolled in a longitudinal cohort were assessed for sequential genital to oral infection with one of nine HPV types (HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58); and then also sequential, same-type oral to genital infection. Incidence rate ratios (IRRs) compared rates of oral HPV among men with and without prior genital infection of the same type. Risk of sequential HPV infections were assessed using Cox proportional hazards model. Incidence of an oral HPV infection was significantly higher among men with a prior genital infection of the same type for any of the 9 HPV types (IRR: 2.3; 95% CI: 1.7-3.0). Hazard ratio of a sequential genital to oral HPV infection was 2.3 (95% CI: 1.7-3.1) and 3.5 (95% CI: 1.9-6.4) for oral to genital infection. Both changed minimally after adjustment for age, country, circumcision, alcohol use, lifetime sexual partners and recent oral sex partners. HPV infections at one site could elevate risk of a subsequent genital or oral HPV infection of the same type in men, emphasizing the importance of vaccination to prevent all HPV infections.