Clonal hematopoiesis in patients with HIV and cancer.

BACKGROUND: Cancer-related deaths for people living with HIV (PWH) are increasing due to longer life expectancies and disparately poor cancer-related outcomes. We hypothesize that advanced biological aging contributes to cancer-related morbidity and mortality for PWH and cancer. We sought to determine the impact of clonal hematopoiesis (CH) on cancer disparities in PWH. METHODS: We conducted a retrospective study to compare the prevalence and clinical outcomes of CH in PWH and people without HIV (PWoH) and cancer. Included in the study were PWH and similar PWoH based on tumor site, age, tumor sequence, and cancer treatment status. Biological aging was also measured using epigenetic methylation clocks. RESULTS: In 136 patients with cancer, PWH had twice the prevalence of CH compared to similar PWoH (23% vs 11%, p=0.07). After adjusting for patient characteristics, PWH were four-times more likely to have CH than PWoH (OR 4.1, 95% CI 1.3-13.9, p=0.02). The effect of CH on survival was most pronounced in PWH, who had a 5-year survival rate of 38% if they had CH (vs 59% if no CH), compared to PWoH who had a 5-year survival rate of 75% if they had CH (vs 83% if no CH). CONCLUSION: This study provides the first evidence that PWH may have a higher prevalence of CH than PWoH with the same cancers. CH may be an independent biological aging risk factor contributing to inferior survival for PWH and cancer.

Human papillomavirus-driven head and neck cancers in Japan during 2008-2009 and 2018-2019: The BROADEN study.

There is limited understanding of epidemiology and time trends of human papilloma virus (HPV)-driven head and neck cancers (HNC) in Japan, especially outside of the oropharynx. To assess HPV-driven HNC, a non-interventional study (BROADEN) of HNC patients diagnosed in 2008-2009 and 2018-2019 was conducted in Japan. Adult patients with oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal or oral cavity cancers were included in this study. HPV was centrally tested using p16INK4a immunohistochemistry, HPV-DNA PCR and HPV E6*I mRNA. HPV attributability required positivity in at least two tests (p16INK4a immunohistochemistry, HPV-DNA PCR, HPV E6*I mRNA) in the oropharynx, and HPV-DNA and HPV E6*I mRNA positivity for non-oropharynx sites. Nineteen hospitals included a total of 1108 patients, of whom 981 had valid samples. Men accounted for 82% of HNC diagnoses. Patients in the earlier cohort were younger and included a higher percentage of smokers. There was an increasing trend of HPV-driven oropharyngeal cancer over the last decade, from 44.2% to 51.7%. HPV attribution in nasopharyngeal cancers was 3.2% in 2008-2009 and 7.5% in 2018-2019; and 4.4% and 0% for larynx respectively. In total, 95.2% of HPV-driven HNC were attributed to HPV genotypes included in the 9-valent HPV vaccine being HPV16 the most prominent genotype. These results suggest that an epidemiologic shift is happening in Japan, with a decrease in smoking and alcohol use and an increase in HPV-driven HNC. The increasing trend of HPV-driven HNC in Japan highlights the need for preventive strategies to mitigate the rise of HPV-driven HNC.

Concordance of Human Papillomavirus Genotypes in Mailed Home-Based Self-Collected Versus Clinician-Collected Anal Swabs Among Sexual and Gender Minority Individuals.

BACKGROUND: Home-based self-sampling may be a viable option for anal cancer screening among sexual minority men (SMM). Yet limited research has compared home-based self-collected with clinician-collected anal swabs for human papillomavirus (HPV) genotyping. METHODS: The Prevent Anal Cancer Self-Swab Study recruited SMM and transgender persons 25 years and over in Milwaukee, WI to participate in an anal cancer screening study. Participants were randomized to a home or clinic arm. Home-based participants were mailed an anal self-sampling kit to complete and return via postal mail. They were also asked to attend a clinic appointment where a clinician collected an anal swab. Swabs were HPV-genotyped using the SPF 10 -LiPA 25 assay. We analyzed 79 paired self and clinician swabs to determine HPV prevalence, percent agreement, and sensitivity and specificity of the mailed home-based anal self-swab to detect HPV genotypes using the clinician-collected swab as the reference. RESULTS: The median number of days between the home and clinic swab was 19 days (range = 2 to 70). Human papillomavirus was detected in 73.3% of self and 75.0% of clinician anal swabs ( P = 0.99). Prevalence of any HPV, any high-risk HPV, any low-risk HPV, and individual HPV types did not significantly differ between self and clinician anal swabs. Agreement between self and clinician swabs was over 90% for 21 of the 25 HPV genotypes. Mailed home-based self-collected swabs had a sensitivity of 94.1% (95% confidence interval, 82.9-99.0) for detection of high-risk HPV versus clinician-collected sampling. CONCLUSIONS: Mailed home-based self-collected and clinician-collected anal swabs demonstrated high concordance for HPV genotyping.

The influence of home versus clinic anal human papillomavirus sampling on high-resolution anoscopy uptake in the Prevent Anal Cancer Self-Swab Study.

Background Anal cancer disproportionately affects sexual and gender minority individuals living with HIV. High-resolution anoscopy (HRA) is an in-clinic procedure to detect precancerous anal lesions and cancer, yet prospective data on factors associated with HRA attendance are lacking. We examined whether anal HPV sampling at home versus in a clinic impacts HRA uptake and assessed HRA acceptability. Methods Sexual and gender minority individuals were randomised to home-based self-sampling or clinical sampling. All were asked to attend in-clinic HRA 1year later. We regressed HRA attendance on study arm using multivariable Poisson regression and assessed HRA acceptability using χ 2 tests. Results A total of 62.8% of 196 participants who engaged in screening attended HRA. Although not significant (P =0.13), a higher proportion of participants who engaged in clinic-based screening attended HRA (68.5%) compared to home-based participants (57.9%). Overall, HRA uptake was higher among participants with anal cytology history (aRR 1.40, 95% CI 1.07-1.82), and lower among participants preferring a versatile anal sex position versus insertive (aRR 0.70, 95% CI 0.53-0.91), but did not differ by race or HIV serostatus. In the clinic arm, persons living with HIV had lower HRA attendance (42.9%) versus HIV-negative participants (73.3%) (P =0.02) and Black non-Hispanic participants had lower HRA attendance (41.7%) than White non-Hispanic participants (73.1%), (P =0.04). No differences in attendance by race or HIV status were observed in the home arm. Conclusions HRA uptake differed significantly by race and HIV status in the clinic arm but not the home arm.

A cross-sectional study of the association of dental health factors with progression and all-cause mortality in men diagnosed with HPV-associated oropharyngeal cancer.

BACKGROUND: Human Papillomavirus-associated oropharyngeal cancer (HPV-OPC) incidence is increasing among men in the United States. Poor dental health has previously been associated with risk of head and neck cancers, oral HPV infection, and persistence but it is not understood whether dental health is associated with outcomes. We sought to determine the association of dental health with progression free survival and overall mortality among men with an HPV-OPC. METHODS: A cross sectional study of men diagnosed with HPV-OPC between 2014-2020 at Moffitt Cancer Center in Tampa, FL was conducted. Dental records were abstracted for assessment of dental fitness prior to cancer treatment. Five dental factors including number of teeth lost, pocket depth, gingival score, loss of attachment, and bone loss were individually examined. Risk factor and outcome data were collected from a patient risk questionnaire and medical record. Using item response theory, an overall dental fitness score from five dental factors was developed in which missing data were multiply imputed. Cox proportional hazards model was used to assess whether dental factors were associated with progression-free survival or overall mortality. RESULTS: Among 206 HPV-OPC cases, median follow-up was 3.4 years (IQR: 2.4-4.4) during which 40 cases involved progression or mortality and 25 deaths occurred. Overall dentition was significantly associated with progression free survival (p = 0.04) and with overall survival (p = 0.03) though findings were not significant after adjustment for age at diagnosis, stage, and smoking history (p = 0.146 and p = 0.120, respectively). A pocket depth of 7 mm or more was associated with overall survival (HR: 5.21; 95% CI: 1.43-19.11) and this remained significant after adjustment for confounding (aHR: 4.14; 95% CI: 1.72-16.26). CONCLUSIONS: Among men diagnosed with an HPV-associated OPC in the US, worse dental health was associated with reduced progression free survival and overall survival, but not after adjustment for confounders. Further studies are needed to examine whether dental health is associated with other prognostic factors and subsequent treatment-related outcomes.

Identification of a Biomarker Panel from Genome-Wide Methylation to Detect Early HPV-Associated Oropharyngeal Cancer.

As oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) increases in men, the need for a screening test to diagnose OPC early is crucial. This study agnostically identified differentially methylated CpG sites to identify additional biomarkers to improve screening for early OPC.DNA was extracted from oral gargles of 89 early cases and 108 frequency matched healthy controls, and processed for genome-wide methylation using the Illumina Infinium MethylationEPIC BeadChip. Selected sites were combined with our prior methylation data in the EPB41L3 gene (CpG sites 438, 427, and 425) and oral HPV16 and HPV18 status were considered as binary variables (positive/negative). Lasso regression identified CpG sites strongly associated with early OPC. ROC curves with AUC were generated. The panel was validated utilizing bootstrap resampling.Machine learning analyses identified 14 markers that are significantly associated with early OPC, including one EPB41L3 CpG site (438) and oral HPV16 status. A final model was trained on all available samples using the discovered panel and was able to predict early OPC compared with controls with an AUC of 0.970 on the training set. In the bootstrap validation sets, the average AUC was 0.935, indicating adequate internal validity.Our data suggest that this panel can detect OPC early, however external validation of this panel is needed. Further refinement of a panel of biomarkers to diagnose OPC earlier is urgently needed to prevent complex treatment of OPC and associated comorbidities, while reducing risk of recurrence. PREVENTION RELEVANCE: This study identified biomarkers using genome-wide methylation to create a panel capable of discerning early oropharyngeal cancer (OPC) from those without OPC. Such a biomarker panel would be an effective tool to detect OPC early and prevent complications of treatment associated with later diagnosis.

Anal human papillomavirus (HPV) disagreement by Linear Array compared to SPF10 PCR-DEIA-LiPA25 system in young sexual minority men.

Introduction: Young sexual minority men (SMM) bear the greatest burden of anal human papillomavirus (HPV) infections. We assessed anal HPV genotype discordance between the Linear Array (LA) and SPF10 PCR-DEIA-LiPA25 (LiPA25). Methods: Discordance was assessed between LA and LiPA25 using self-collected anal swabs from 120 SMM aged 18-29 who were recruited in 2014-2016. Multiple-type infection was explored as a potential confounder of testing agreement, along with clinical and behavioral factors such as HIV status, syphilis status, incarceration history, health insurance coverage, having 3 or more sex partners in the past 6 months, and co-infection with HPV-16. Results: Significant discordance was found for HPV-6, -11, -16, -31, -42, -54, and -59. Exploratory analyses suggest higher prevalence of genotype discordance in those living with HIV, those with 3 or more sex partners, and those who were positive for 4 or more HPV types. Conclusions: Our results highlight the importance of HPV detection methods which may inform different interpretations of research assessing anal HPV natural history among SMM at highest risk for HPV.

A clinical overview of people living with HIV and genitourinary cancer care.

The number of people living with HIV infection has been increasing globally. Administration of antiretroviral therapy is effective in controlling the infection for most patients and, as a consequence, people living with HIV (PLWH) now often have a long life expectancy. However, their risk of developing cancer - most notably virus-related cancers - has been increasing. To date, few studies have assessed the risk of genitourinary cancers in PLWH, and robust scientific data on their treatment-related outcomes are lacking. Previous studies have noted that PLWH are at a reduced risk of prostate cancer; however, low adoption and/or availability of prostate cancer screening among these patients might be confounding the validity of this finding. In genitourinary cancers, advanced stage at diagnosis and reduced cancer-specific mortality have been reported in PLWH. These data likely reflect, at least in part, the inequity of health care access for PLWH. Notably, systemic chemotherapy and/or radiotherapy could decrease total CD4+ cell counts, which could, therefore, increase the risk of morbidity and mortality from cancer treatments in PLWH. Immune checkpoint inhibitors have become the therapeutic backbone for many advanced malignancies in the general population; however, most studies validating their efficacy have excluded PLWH owing to concerns of severe adverse effects from immune checkpoint inhibitors themselves and/or related to their immunosuppressed status. To our knowledge, no genitourinary cancer survivorship programme exists that specifically caters to the needs of PLWH. By including PLWH in ongoing cancer trials, we can gain invaluable insights that will help to improve cancer care specifically for PLWH.

Differences in Provider Hepatitis C Virus Screening Recommendations by Patient Risk Status.

Providers' recommendation is among the strongest predictors to patients engaging in preventive care. Therefore, the aim of this study was to compare providers' Hepatitis C Virus (HCV) screening recommendation quality between high-risk and average-risk patients to determine if providers are universally recommending HCV screening, regardless of risk behaviors. This cross-sectional survey of 284 Indiana providers in 2020 assessed provider characteristics, HCV screening recommendation practices (strength, presentation, frequency, timeliness), self-efficacy, and barriers to recommending HCV screening. T-test and Chi-square compared recommendation practices for high-risk and average-risk patients. Prevalence ratios were calculated for variables associated with HCV recommendation strength comparing high-risk and average-risk patients. Logistic regression analyses examined factors associated with HCV recommendation strength for high- and average-risk patients, with odds ratios. Compared to average-risk patients, high-risk patients received higher proportion of HCV recommendations that were strong (70.4 % v. 42.4 %), routine (61.9 % v. 55.6 %), frequent (37.7 % v. 28 %), and timely (74.2 % v. 54.9 %) (P-values < 0.001). Compared to average-risk patients, providers with high-risk patients had a lower percentage of giving a strong recommendation if they were nurse practitioner (PR = 0.49). For high-risk patients, providers with higher self-efficacy (aOR = 2.16;95 %CI = 0.99-4.69) had higher odds, while those with higher perceived barriers (aOR = 0.19;95 %CI = 0.09-0.39) and those with an internal medicine specialty compared to family medicine (aOR = 0.22;95 %CI = 0.08-0.57) had lower odds of giving a strong recommendation. These data suggest providers are not universally recommending HCV screening for all adults regardless of reported risk. Future research should translate these findings into multilevel interventions to improve HCV screening recommendations regardless of patient risk status.

Factors associated with parental human papillomavirus vaccination intentions among adolescents from socioeconomically advantaged versus deprived households: a nationwide, cross-sectional survey.

Background: In the USA, HPV vaccine coverage is substantially lower among adolescents from high-income households compared to their low-income counterparts. We examined and compared the factors associated with parental HPV vaccination intentions between socioeconomically divergent groups. Methods: Data from unvaccinated and not fully HPV-vaccinated adolescents from the 2017-2021 National Immunization Survey (NIS)-Teen were analyzed. Socioeconomically advantaged vs. deprived groups were identified based on dichotomized income (material capital) and education (social capital). Parental intent to initiate and complete the HPV vaccine series was compared using bivariable analysis and the factors associated with lacking intent were identified. Findings: The 2017-2021 NIS-Teen included a total of 212,643 participants; the final analytical sample consisted of 105,958 adolescents (an estimated 10.3 million adolescents) who were unvaccinated or not fully vaccinated. In the advantaged group, 64.7% of parents of unvaccinated adolescents (equating to 2.4 million US adolescents) had no intention to initiate the HPV vaccine compared to 40.9% of parents in the deprived group (equating to 0.2 million adolescents) (P < 0.0001; S > 13.29). The most frequent reason for lacking intent in the advantaged group was 'safety concerns' (25.5%). In the deprived group, 'lack of knowledge', 'not recommended', and 'not needed' were common reasons (nearly 15% each). Lack of intent to complete the HPV vaccine series was higher in the advantaged group (43.9%; 1.1 million adolescents) compared to the deprived group (25.2%; 0.08 million adolescents) (P < 0.0001; S > 13.29). More than half in the advantaged group (58.4%) and over a third (37.1%) in the deprived group cited 'already up to date' as the main reason for not completing the HPV vaccine series. Interpretation: Lack of intent to initiate and complete the HPV vaccination series, particularly among socioeconomically advantaged parents is a significant barrier to achieving the national goal in the USA. Funding: The US National Institute on Minority Health and Health Disparities, the National Center for Advancing Translational Sciences, MUSC Hollings Cancer Center Seed funding, and the US National Cancer Institutes.

Engagement and factors associated with annual anal human papillomavirus screening among sexual and gender minority individuals.

Objectives: Annual screening with a provider has been recommended for groups at highest risk for anal cancer. Anal self-sampling could help address screening barriers, yet no studies have examined annual engagement with this method. Methods: The Prevent Anal Cancer Self-Swab Study recruited sexual and gender minority individuals 25 years and over who have sex with men in Milwaukee, Wisconsin to participate in an anal cancer screening study. Participants were randomized to a home or clinic arm. Home-based participants were mailed an anal human papillomavirus self-sampling kit at baseline and 12 months, while clinic-based participants were asked to schedule and attend one of five participating clinics at baseline and 12 months. Using Poisson regression, we conducted an intention-to-treat analysis of 240 randomized participants who were invited to screen at both timepoints. Results: 58.8% of participants completed annual (median=370 days) anal screening. When stratified by HIV status, persons living with HIV had a higher proportion of home (71.1%) versus clinic (22.2%) annual screening ( p <0.001). Non-Hispanic Black participants had a higher proportion of home-based annual anal screening engagement (73.1%) compared to annual clinic screening engagement (31.6%) ( p =0.01). Overall, annual screening engagement was significantly higher among participants who had heard of anal cancer from an LGBTQ organization, reported "some" prior anal cancer knowledge, preferred an insertive anal sex position, and reported a prior cancer diagnosis. Annual screening engagement was significantly lower for participants reporting a medical condition. Conclusions: Annual screening engagement among those at disproportionate anal cancer risk was higher in the home arm.

Epstein-Barr Virus DNA Is Associated With Conjunctival Squamous Cell Carcinomas: A Case-Control Study From Zimbabwe.

Incidence of conjunctival squamous cell carcinoma (cSCC) in Zimbabwe is >30-fold higher than the global average. cSCC risk is notably higher among people with human immunodeficiency virus, implicating impaired immune response and a yet unknown infectious etiology. Formalin-fixed, paraffin-embedded blocks from Zimbabwe, comprising conjunctival precancer (n = 78), invasive cSCC cases (n = 148) and nonmalignant eye lesions (n = 119), were tested for multiple DNA viruses using Luminex bead-based technology. Epstein-Barr virus (EBV) type 1 positivity was strongly associated with cSCC diagnosis (adjusted odds ratio [aOR], 5.6 [95% confidence interval {CI}, 3.0-10.4) and marginally associated with precancer (aOR, 2.1 [95% CI, 1.0-4.5]). On analyzing EBV transcriptional activity with any of LMP1, EBNA1, and BZLF1, RNA transcripts were detected in 5 of 112 controls, 3 of 67 precancers, and 10 of 139 cases and none were associated with conjunctival case status. Our EBV DNA data suggest that EBV may play a role in cSCC. However, the low detection rate of EBV RNA supports further investigation to infer causality.

The influence of home versus clinic anal human papillomavirus sampling on high-resolution anoscopy uptake in the Prevent Anal Cancer Self-Swab Study.

Background: Anal cancer disproportionately affects men who have sex with men (MSM) living with HIV. High-resolution anoscopy (HRA) is an in-clinic procedure to detect precancerous anal lesions and cancer, yet prospective data on factors associated with HRA attendance are lacking. We examined whether anal HPV sampling at home versus in a clinic impacts HRA uptake and assessed HRA acceptability. Method: MSM and trans persons 25 years and older were randomized to home-based self-sampling or clinical sampling. All were asked to attend in-clinic HRA one year later. We regressed HRA attendance on study arm using multivariable Poisson regression and assessed HRA acceptability using χ 2 tests. Results: 62.8% of 196 participants who engaged in screening attended HRA. Although not significant ( p =0.13), a higher proportion of participants who engaged in clinic-based screening attended HRA (68.5%) compared to home-based participants (57.9%). Overall, HRA uptake was higher among participants with anal cytology history (aRR 1.44, 95% CI 1.11 - 1.87) and lower among participants preferring versatile anal sex position versus insertive (aRR 0.70, 95% CI 0.53 - 0.91), but did not differ by race or HIV serostatus. In the clinic arm, persons living with HIV had lower HRA attendance (42.9%) versus HIV-negative participants (73.3%) ( p =0.02) and Black non-Hispanic participants had lower HRA attendance (41.7%) than White non-Hispanic participants (73.1%), ( p =0.04); however, no differences in attendance by race or HIV status were observed in the home arm. Conclusions: HRA uptake differed significantly by race and HIV status in the clinic arm but not the home arm.

Neutralizing Antibody Response following a Third Dose of the mRNA-1273 Vaccine among Cancer Patients.

Cancer patients are at an increased risk of morbidity and mortality from SARS-CoV-2 infection and have a decreased immune response to vaccination. We conducted a study measuring both the neutralizing and total antibodies in cancer patients following a third dose of the mRNA-1273 COVID-19 vaccine. Immune responses were measured with an enzyme-linked immunosorbent assay (ELISA) and neutralization assays. Kruskal-Wallis tests were used to evaluate the association between patient characteristics and neutralization geometric mean titers (GMTs), and paired t-tests were used to compare the GMTs between different timepoints. Spearman correlation coefficients were calculated to determine the correlation between total antibody and neutralization GMTs. Among 238 adults diagnosed with cancer, a third dose of mRNA-1273 resulted in a 37-fold increase in neutralization GMT 28 days post-vaccination and maintained a 14.6-fold increase at 6 months. Patients with solid tumors or lymphoid cancer had the highest and lowest neutralization GMTs, respectively, at both 28 days and 6 months post-dose 3. While total antibody GMTs in lymphoid patients continued to increase, other cancer types showed decreases in titers between 28 days and 6 months post-dose 3. A strong correlation (p < 0.001) was found between total antibody and neutralization GMTs. The third dose of mRNA-1273 was able to elicit a robust neutralizing antibody response in cancer patients, which remained for 6 months after administration. Lymphoid cancer patients can benefit most from this third dose, as it was shown to continue to increase total antibody GMTs 6 months after vaccination.

Incidence of external genital lesions related to human papillomavirus among Mexican men. A cohort study / Incidencia de lesiones genitales externas relacionadas con el virus del papiloma humano entre hombres mexicanos. Un estudio de cohorte

Abstract: Objective: To determine external genital lesion (EGL) incidence -condyloma and penile intraepithelial neoplasia (PeIN)- and genital HPV-genotype progression to these EGLs. Materials and methods: Participants (healthy males 18-74y from Cuernavaca, Mexico, recruited 2005-2009, n=954) underwent a questionnaire, anogenital examination, and sample collection every six months; including excision biopsy on suspicious EGL with histological confirmation. Linear array assay PCR characterized 37 high/low-risk HPV-DNA types. EGL incidence and cumulative incidence were calculated, the latter with Kaplan-Meier. Results: EGL incidence was 1.84 (95%CI=1.42-2.39) per 100-person-years (py); 2.9% (95%CI=1.9-4.2) 12-month cumulative EGL. Highest EGL incidence was found in men 18-30 years: 1.99 (95%CI=1.22-3.25) per 100py. Seven subjects had PeIN I-III (four with HPV16). HPV11 most commonly progresses to condyloma (6-month cumulative incidence=44.4%, 95%CI=14.3-137.8). Subjects with high-risk sexual behavior had higher EGL incidence. Conclusion: In Mexico, anogenital HPV infection in men is high and can cause condyloma. Estimation of EGL magnitude and associated healthcare costs is necessary to assess the need for male anti-HPV vaccination.

Resumen: Objetivo: Determinar incidencia de lesiones genitales externas (LGE) -condiloma y neoplasia intraepitelial del pene (NIP)- y progresión de genotipos de VPH a LGE. Material y métodos: Se aplicaron cuestionarios, examen anogenital y recolección de muestras cada seis meses a hombres sanos (18-74 años, de Cuernavaca, México, reclutados 2005-2009, n=954) con biopsia y confirmación histológica. Se caracterizaron 37 tipos de ADN-VPH; se calculó incidencia de LGE (cumulativa con Kaplan-Meier). Resultados: Incidencia de LGE=1.84 (IC95%=1.42-2.39) por 100-persona-años (pa); 2.9% (IC95%=1.9-4.2) LGE acumulativa a 12 meses. Mayor incidencia de LGE entre hombres 18-30 años; 1.99 (IC95%=1.22-3.25) por 100pa. Siete sujetos tuvieron NIP I-III. VPH-11 más comúnmente progresa a condiloma (incidencia acumulativa a seis meses=44.4%, IC95%=14.3-137.8). Los sujetos con comportamiento sexual de alto riesgo tuvieron mayor incidencia de LGE. Conclusiones: En México la infección anogenital con VPH es alta y puede causar condiloma. La estimación de magnitud de LGE y los costos sanitarios asociados se necesita para evaluar la necesidad de vacunación contra VPH en hombres.

Prevalence and incidence of anal human papillomavirus infection in Mexican men: Need for universal prevention policies / Prevalencia e incidencia de infección por virus de papiloma humano en canal anal en hombres mexicanos: Necesidad de políticas de prevención universal

Abstract: Objective: Describe the natural history of anal HPV among men. Materials and methods: Prospective study among men 18-70 years (n=665), from Cuernavaca, Mexico who completed questionnaires and provided specimens (HPV genotyped) at enrollment and 1+ follow-up visit. HPV prevalence and incidence were estimated. Prevalence ratios were calculated with Poisson regression using robust variance estimation. Person-time for incident HPV infection was estimated using number of events modeled as Poisson variable for total person-months. Results: Anal infection prevalence: any HPV type=15%, high-risk=8.4%, HPV16=1.4%, tetravalent vaccine types (4vHPV)=4.4%, nonavalent vaccine types (9vHPV)=6.3%. Factors associated with prevalence: 50+ lifetime female sex partners (adjusted prevalence ratio, a PR=3.25, 95% CI:1.12-9.47), 10+ lifetime male sex partners (aPR=3.06, 95%CI:1.4-6.68), and 1+ recent male anal sex partners (aPR=2.28, 95%CI:1.15-4.5). Anal incidence rate: high-risk HPV=7.8/1 000 person-months (95%CI:6.0-10.1), HPV16=1.8/1 000 person-months (95%CI:1.1-2.9),4vHPV=3.4/1 000 person-months (95%CI:2.3-4.9) and 9vHPV=5.5/1000 person-months (95%CI:4.1-7.5). Conclusions: Implementation of universal HPV vaccination programs, including men, is a public health priority.

Resumen: Objetivo: Generar evidencia que apoye la vacunación universal contra VPH. Material y métodos: Estudio prospectivo con hombres 18-70 años (n=665) de Cuernavaca, México con cuestionarios y genotipificación de VPH en muestras (2+mediciones). Se estimó prevalencia e incidencia; se calcularon tasas de prevalencia con regresión Poisson. Se estimó persona-tiempo para infecciones incidentes. Resultados: Prevalencia de infección anal: cualquier tipo de VPH=15%, alto-riesgo=8.4%, VPH16=1.4%, tipos en vacuna tetravalente=4.4% y tipos en vacuna nonavalente=6.3%. Factores asociados con infección prevalente: 50+ parejas sexuales femeninas en la vida (tasa de prevalencia ajustada, TPa=3.25, IC95%:1.12-9.47); 10+ parejas sexuales masculinas en la vida (TPa=3.06, IC95%:1.4-6.68) y 1+ parejas masculinas (sexo anal) recientes (TPa=2.28, IC95%:1.15-4.5). Tasas de incidencia para infección anal: VPH alto-riesgo=7.8/1000 persona-meses (IC95%:6.0-10.1), VPH 16=1.8/1000 persona-meses (95%IC:1.1-2.9), tipos en vacuna tetravalente=3.4/1000 persona-meses y tipos en vacuna nonavalente=5.5/1000 persona-meses. Conclusiones: Implementación de programas de vacunación universal (incluyendo hombres) contra VPH es una prioridad en salud pública.

Prevention and control of neoplasms associated with HPV in high-risk groups in Mexico City: The Condesa Study / Prevención y control de neoplasias asociadas a VPH en grupos de alto riesgo de la Ciudad de México: el Estudio Condesa

Abstract: Objective: To evaluate the effectiveness of a combined strategy of human papillomavirus virus (HPV) vaccination and high-risk HPV screening to reduce the occurrence of anogenital and oropharyngeal neoplasms among men who have sex with men, people with HIV, homeless people, transgender women, female sex workers and rape victims. Materials and methods: This mixed methods study evaluates the effectiveness of a combined vaccination-screening strategy to reduce HPV prevalence/incidence and occurrence of cervical intraepithelial neoplasms grade 2+ and/or anal intraepithelial neoplasms grade 2+, using Kaplan-Meier. The time-to-event method will evaluate time from positive results for specific anogenital HPV to incidence of anogenital lesions containing that HPV type. Results: People vaccinated against HPV and screened for HPV as a primary test will have lower prevalence and incidence of HPV infection and consequently lower frequency of HPV-related anogenital and oropharyngeal lesions. Conclusions: This study will generate scientific evidence on effectiveness of a combined vaccination-screening strategy to reduce the burden of HPV-associated neoplasms.

Resumen: Objetivo: Evaluar la efectividad de una estrategia combinada de vacunación contra el virus de papiloma humano (VPH) y tamizaje de VPH de alto riesgo para reducir neoplasias anogenitales y orofaringeas entre hombres que tienen sexo con hombres, personas con VIH, personas en situación de calle, mujeres transgénero, trabajadoras sexuales y víctimas de violación. Material y métodos: Este estudio evaluará la efectividad de una estrategia combinada de vacunación y tamizaje para reducir la ocurrencia de neoplasias intraepiteliales cervicales grado 2+ o neoplasias intraepiteliales anales grado NIA2+ utilizando Kaplan-Meier. Se evaluará tiempo de resultados positivos para tipos específicos de VPH anogenital a incidencia de lesiones anogenitales con ese tipo de VPH. Resultados: Las personas vacunadas contra VPH y con tamizaje de VPH tendrán menor prevalencia e incidencia de infecciones por VPH y por ende menor frecuencia de lesiones anogenitales y orofaringeas relacionadas con VPH. Conclusiones: Este estudio generará evidencia científica sobre la efectividad de una estrategia combinada de vacunación y tamizaje para reducir la carga de neoplasias asociadas al VPH.

Design and results of the USA-Mexico border human papillomavirus (HPV), cervical dysplasia, and chlamydia trachomatis study / Diseño y resultados del estudio sobre los papilomavirus humanos (PVH), la displasia cervical y Chlamydia trachomatis en la frontera de Estados Unidos y México

México tiene una de las mayores tasas mundiales de mortalidad por cáncer cervical invasor, sobre todo en los estados del norte que tienen frontera con los Estados Unidos de América (EE.UU). Además, los hispanos residentes en los Estados Unidos tienen mayores tasas que los no hispanos de este país. Considerando esta situación, se formó un equipo de ambos países para analizar el problema y determinar la prevalencia y factores de riesgos de la displasia cervical y de la infección por papilomavirus humanos (PVH), una enfermedad de transmisión sexual que se sabe que causa cáncer. También se analizó la infección por Chlamydia trachomatis, una enfermedad de transmisión sexual frecuente que podría constituir un cofactor de los PVH. Métodos. La investigación, realizada EN 1997 Y 1998 en la zona fronteriza de los estados de Arizona (EE.UU) y Sonora (México), consistió en un estudio transversal de 2436 mujeres (media de 33,3 mas o menos 10,3 años) que acudían a consultas ginocológicas de rutina. Se efectuaron frotis cervicales de Papanicolaou y pruebas de detcción de la infección por PVH, mediante la reacción en cadena de la polimerasa (PCR) y la captación de híbridos (HC), y la infección por C. trachomatis, mediante HC e inmunoanálisis enzimático (EIA) Resultados. La prevalencia gobal de exámenes citológicox anormales fue del 9,3 por ciento la diferencia entre México (11,4 por ciento) y EE.UU.(6,6 por ciento) fue significativa. Un 14,5 por ciento de las participantes fueron positivas para los PVH en las PCR, sin que ubiera diferencias entre los dos países, y esto a pesar de que las mujeres mejicanas tenían menores riesgos relacionados con la conducta. La prevalencia global de C. trachomatis fue mayor con la HC que con el EIA (8,2 por ciento frente a 3,0 por ciento) y fue mayor en México que en EE.UU. con ambos métodos. Conclusiones. Un importante logro de este proyecto consistió en la puesta en marcha de un programa de control de la calidad de la recolección de los frotis de Papanicolaou que dio lugar a una notable reducción de los frotis inadecuados en México. A pesar de numerosas posibles barreras logísticas, el equipo de los dos países consiguió realizar con éxito un estudio a gran escala en el área fronteriza y desarrollar la infraestructura para futuras investigaciones

Objective. Mexico has one of the highest mortality rates of invasive cervical cancer in the world. This is particularly true for the states in northern Mexico that border on the United States of America. In addition, Hispanics in the United States have higher rates than do non-Hispanics in the country. Therefore, a binational team was formed to focus on this problem and to determine the risk factors and prevalence of cervical dysplasia and human papillomavirus (HPV) infection, the sexually transmitted disease (STD) known to cause cervical cancer. Chlamydia trachomatis infection, a common STD and potential HPV cofactor, was also assessed. Methods. Research was conducted in 1997 and 1998 in the border region of two states, Arizona in the United States and Sonora in Mexico, applying a cross-sectional study of women attending clinics for routine gynecologic care. Clinical measurements included Pap smears, HPV infection by both polymerase chain reaction (PCR) and Hybrid Capture (HC), and C. trachomatis status by HC and enzyme-linked immunoassay (EIA). A total of 2 436 women were enrolled (mean age 33.3 years ± 10.3 years). Results. The overall prevalence of abnormal cytology was 9.3%, with a significant difference in the prevalence in Mexico (11.4%) vs. the United States (6.6%). Of the participants, 14.5% of them tested positive for HPV by PCR, with no significant difference between the two countries, in spite of a lower behavioral risk profile for the Mexican women. Overall prevalence of C. trachomatis was found to be greater by HC than by EIA (8.2% vs. 3.0%), and in Mexico higher by both methods. Conclusions. An important accomplishment of the project was the implementation of a quality control program for Pap smear collection, which resulted in a significant reduction in inadequate smears in Mexico. Despite numerous potential logistical barriers, the binational team successfully conducted a large-scale study in the border area and developed an infrastructure for future research.