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.

Incidence of external genital lesions related to human papillomavirus among Mexican men. A cohort study.

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 inci- dence 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). Subject with high-risk sexual behavior had higher EGL incidence. CONCLUSIONS: 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.

OBJETIVO: Determinar incidencia de lesiones genitales externas (LGE) ­condiloma y neoplasia intraepitelial del pene (NIP)­ y progresión de genotipos deVPH 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 caracteri- zaron 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 conVPH 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.

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=7.8/1000 person-months (95%CI:6.0-10.1), HPV16=1.8/1000 personmonths (95%CI:1.1-2.9),4vHPV=3.4/1000 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.

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%, altoriesgo=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: mplementación de programas de vacunación universal (incluyendo hombres) contra VPH es una prioridad en salud pública.

The Impact of Music Therapy on Anxiety in Cancer Patients Undergoing Simulation for Radiation Therapy.

PURPOSE: Radiation therapy (RT) is associated with high stress levels. The role of music therapy (MT) for patients receiving RT is not well described. This study evaluates the impact of MT on anxiety and distress during simulation in patients with newly diagnosed head and neck or breast cancer. METHODS AND MATERIALS: This institutional review board-approved randomized trial of MT versus no MT at the time of simulation included the pre-State-Trait Anxiety Inventory (STAI-S Anxiety) questionnaire and Symptom Distress Thermometer (SDT). Patients randomized to MT received a consultation with a music therapist, during which music of the patients' choice to be played during simulation was selected. The no-MT patients did not receive the MT consultation, nor did they hear prerecorded music during simulation. Subsequent to the simulation, all patients repeated the STAI-S Anxiety questionnaire and the SDT. RESULTS: Of the 78 patients enrolled (39 in MT group and 39 in no-MT group), 38 had breast cancer and 40 had head and neck cancer. The male-female ratio was 27:51. The overall mean pre- and post-simulation STAI-S scores were 38.7 (range, 20-60) and 35.2 (range, 20-72), respectively. The overall mean pre- and post-simulation SDT scores were 3.2 (range, 0-10) and 2.5 (range, 0-10), respectively. The MT group had mean pre- and post-simulation STAI-S scores of 39.1 and 31.0, respectively (P<.0001), and the mean SDT scores before and after simulation were 3.2 and 1.7, respectively (P<.0001). The no-MT group's mean pre- and post-simulation STAI-S scores were 38.3 and 39.5, respectively (P=.46), and the mean SDT scores were 3 and 3.2, respectively (P=.51). CONCLUSIONS: MT significantly lowered patient anxiety and distress during the simulation procedure on the basis of the STAI-S questionnaire and SDT. Incorporating culturally centered individualized MT may be an effective intervention to reduce stressors. Continued research defining the role of MT intervention in improving the patient experience by reducing anxiety is warranted.

HPV SEROSTATUS PRE- AND POST-VACCINATION IN A RANDOMIZED PHASE II PREPAREDNESS TRIAL AMONG YOUNG WESTERN CAPE, SOUTH AFRICAN WOMEN: THE EVRI TRIAL.

BACKGROUND: HPV antibodies are a marker of past exposure to the virus. Our objective was to assess HPV serostatus pre- and post-vaccination among HIV-negative women. METHODS: Women aged 16-24 years old were randomized in a placebo controlled trial utilizing the 4-valent HPV (4vHPV) vaccine (NCT01489527, clinicaltrials.gov). Participants (n=389) received the 4vHPV vaccine or placebo following a three dose schedule. Sera were collected at Day 1 and Month 7 for assessment of HPV 6, 11, 16, and 18 neutralizing antibody levels using a multiplex competitive Luminex immunoassay (Merck) based on detecting the L1 capsid antigen for each HPV type. RESULTS: Seroprevalence was 73% for HPV6, 47% for HPV11, 33% for HPV16, and 44% for HPV18. Seroprevalence for any HPV type did not significantly differ by age or lifetime number of partners. The majority of participants (64%) had two or more 4vHPV antibodies present at enrollment and 12% had antibodies to all four. Among women in the vaccine arm, those that were seropositive for HPV16 at enrollment had higher titers at month 7 compared to women that were seronegative for HPV16 at enrollment; this trend holds for the other HPV types as well. Seroconversion among baseline seronegative participants in the placebo group ranged from 5% for HPV16 to 23% for HPV6. CONCLUSION: HPV seroprevalence was high in this population, emphasizing the need to vaccinate prior to sexual debut.

Comparison of the Natural History of Genital HPV Infection among Men by Country: Brazil, Mexico, and the United States.

Background: Male genital human papillomavirus (HPV) prevalence and incidence has been reported to vary by geographical location. Our objective was to assess the natural history of genital HPV by country among men with a median of 48 months of follow-up.Methods: Men ages 18-70 years were recruited from United States (n = 1,326), Mexico (n = 1,349), and Brazil (n = 1,410). Genital specimens were collected every 6 months and HPV genotyping identified 37 HPV genotypes. Prevalence of HPV was compared between the three countries using the Fisher exact test. Incidence rates and 95% confidence intervals were calculated. The median time to HPV clearance among men with an incident infection was estimated using the Kaplan-Meier method.Results: The prevalence and incidence of the genital HPV types known to cause disease in males (HPV 16 and 6) was significantly higher among men from Brazil than men from Mexico. Prevalence and incidence of those genital HPV types in the United States varied between being comparable with those of Mexico or Brazil. Although genital HPV16 duration was significantly longer in Brazil (P = 0.04) compared with Mexico and the United States, HPV6 duration was shortest in Brazil (P = 0.03) compared with Mexico and the United States.Conclusions: Men in Brazil and Mexico often have similar, if not higher prevalence of HPV compared with men from the United States.Impact: Currently, there is no routine screening for genital HPV among males and while HPV is common in men, and most naturally clear the infection, a proportion of men do develop HPV-related diseases. Men may benefit from gender-neutral vaccine policies. Cancer Epidemiol Biomarkers Prev; 26(7); 1043-52. ©2017 AACR.

Comparison of anal HPV natural history among men by country of residence: Brazil, Mexico, and the United States.

OBJECTIVES: Globally, anal cancer incidence is rare, but is increasing in some world regions. Our objective was to assess differences in anal HPV natural history in three countries. METHODS: Men aged 18-70 years were recruited from the US (n = 634), Mexico (n = 665), and Brazil (n = 731). Anal specimens were collected every six-months. HPV genotyping was assessed by Linear Array. Anal HPV prevalence was compared using the Fisher's exact test. HPV infection incidence rates (IR) and 95% confidence intervals (CI) were calculated. RESULTS: Any anal HPV prevalence was highest among men from Brazil (24%) compared to Mexico (15%) and the US (15%). When stratified by sexual history, the prevalence of any HPV among MSM/MSMW was 43%, 37%, and 45% and 9%, 12%, and 10% for MSW from Brazil, Mexico, and US, respectively. Any HPV incidence was significantly higher among men from Brazil compared to US men (IRR = 2.4, 95% CI = 1.7-3.4) and comparable between men from Mexico and the US (IRR = 1.2, 95% CI = 0.8-1.8). CONCLUSION: Men in Brazil and Mexico often have similar, if not higher incidence of anal HPV compared to men from the U.S., and may benefit from gender neutral HPV vaccine policies.

Country-specific HPV-related genital disease among men residing in Brazil, Mexico and The United States: The HIM study.

The purpose of this study was to assess whether the incidence of histopathologically confirmed condyloma and penile intraepithelial neoplasia (PeIN) and rates of genital HPV infection progression to these lesions differs by country (Brazil, Mexico and the U.S.). At each visit, lesions were biopsied and were categorized by pathologic diagnoses. The Linear Array genotyping method was used to identify HPV genotypes from genital swabs, while the INNO-LiPA HPV Genotyping Extra method was used for tissue specimens. Age-specific analyses were conducted for lesion incidence by country, with Kaplan-Meier estimation of cumulative incidence. The proportion of HPV infections that progressed to condyloma and PeIN, the median time to lesion development and the incidence rates were estimated by country. When comparing demographic and sexual characteristics across the three countries, sexual orientation (p = 0.008) and lifetime number of female sexual partners (p < 0.0001) were differentially associated with lesion incidence in the three countries. Condyloma incidence in Brazil and the U.S. decreased with age, while incidence remained constant across the lifespan in Mexico. There were no differences by country and age for PeIN incidence. HPV types 6 and 11 were the most common types to progress to condyloma and HPV types 16, 6 and 11 were the most common types to progress to PeIN in all three countries. The continuous risk of condyloma and PeIN across all age groups and countries in this study emphasizes the need to ensure that strong HPV immunity, such as that obtained through vaccination, is maintained across the lifespan of men.

Seroprevalence of cutaneous human papillomaviruses (HPVs) among men in the multinational HPV Infection in Men study.

Data on cutaneous human papillomavirus (HPV) seroprevalence are primarily derived from skin cancer case-control studies. Few studies have reported the seroprevalence of cutaneous HPV among healthy men. This study investigated the seroprevalence of cutaneous HPV types and associated risk factors among men residing in Brazil, Mexico and the USA. Six hundred men were randomly selected from the HPV Infection in Men study. Archived serum specimens were tested for antibodies against 14 cutaneous HPV genotypes, ß-HPV types (5/8/12/14/17/22/23/24/38/48), α-HPV 27, γ-HPV 4, µ-HPV1 and ν-HPV 41 using a glutathione S-transferase L1-based multiplex serology assay. Risk factor data were collected by a questionnaire. Binomial proportions were used to estimate seroprevalence, and logistic regression to examine factors associated with seropositivity. Overall, 65.4 % of men were seropositive to ≥1 of the 14 cutaneous HPV types, and 39.0 % were positive for ≥1 ß-HPV types. Seroprevalence was 8.9, 30.9, 28.6 and 9.4 % for α-HPV 27, γ-HPV 4, µ-HPV 1 and ν-HPV 41, respectively. In multivariate analyses, seropositivity for any cutaneous HPV type was associated with higher education [adjusted odds ratio (AOR) 1.75; 95 % confidence interval (CI) 1.08-2.83], and seropositivity of any ß-HPV type was significantly associated with increasing age (AOR 1.72; 95 % CI 1.12-2.63, for men aged 31-44 years vs men aged 18-30 years). Other factors associated with various type-specific cutaneous HPV seropositivity included country, circumcision and lifetime number of male sexual partners. These data indicate that exposure to cutaneous HPV is common. Future studies are needed to assess the role of cutaneous HPV in diseases.

Cutaneous beta human papillomaviruses and the development of male external genital lesions: A case-control study nested within the HIM Study.

BACKGROUND: Cutaneous human papillomaviruses (HPVs) increase the risk of non-melanoma skin cancer in sun-exposed skin. We examined the role of beta-HPV in the development of male external genital lesions (EGLs), a sun-unexposed site. METHODS: In this nested case-control study (67 men with pathologically-confirmed EGLs and 134 controls), exfoliated cells collected from the surface of lesions and normal genital skin 0, 6, and 12 months preceding EGL development were tested for beta-HPV DNA using a type-specific multiplex genotyping assay. Beta-HPV prevalence was estimated and conditional logistic regression was used to evaluate the association with condyloma, the most common EGL. RESULTS: While beta-HPV prevalence among controls remained stable, the prevalence among cases was lowest on the surface of lesion. Detecting beta-HPV on the normal genital skin was not associated with the presence or development of condyloma. CONCLUSIONS: Cutaneous beta-HPV does not appear to be contributing to pathogenesis in male genital skin.

Quadrivalent Human Papillomavirus (HPV) Vaccine Induces HPV-Specific Antibodies in the Oral Cavity: Results From the Mid-Adult Male Vaccine Trial.

BACKGROUND: Human papillomavirus virus type 16 (HPV-16) and HPV-18 cause a large proportion of oropharyngeal cancers, which are increasing in incidence among males, and vaccine efficacy against oral HPV infections in men has not been previously evaluated. METHODS: Sera and saliva collected in mouthwash and Merocel sponges at day 1 and month 7 were obtained from 150 men aged 27-45 years from Tampa, Florida, and Cuernavaca, Mexico, who received Gardasil at day 1 and months 2 and 6. Specimens were tested for anti-HPV-16 and anti-HPV-18 immunoglobulin G (IgG) levels by an L1 virus-like particle-based enzyme-linked immunosorbent assay. RESULTS: All participants developed detectable serum anti-HPV-16 and anti-HPV-18 antibodies, and most had detectable antibodies in both oral specimen types at month 7 (HPV-16 was detected in 93.2% of mouthwash specimens and 95.7% of sponge specimens; HPV-18 was detected in 72.1% and 65.5%, respectively). Antibody concentrations in saliva were approximately 3 logs lower than in serum. HPV-16- and HPV-18-specific antibody levels, normalized to total IgG levels, in both oral specimen types at month 7 were significantly correlated with serum levels (for HPV-16, ρ was 0.90 for mouthwash specimens and 0.92 for sponge specimens; for HPV-18, ρ was 0.89 and 0.86, respectively). CONCLUSIONS: This is the first study demonstrating that vaccination of males with Gardasil induces HPV antibody levels at the oral cavity that correlate with circulating levels.

Impact of Serum Antibodies to HPV Serotypes 6, 11, 16, and 18 to Risks of Subsequent Genital HPV Infections in Men: The HIM Study.

Naturally induced serum antibodies against human papillomavirus (HPV) may affect risks of subsequent incident genital infections by HPV 6, 11, 16, or 18 in men. In this study, we examined the hypothesis by following 4,123 healthy men every 6 months (median follow-up time, 4.1 years). HPV antibodies were measured at baseline using a virus-like particle-based ELISA assay. Genital HPV genotypes were detected using Roche Linear Array. Incidence proportions and 6-month persistence proportions were calculated at 6-month intervals. Kaplan-Meier curves and Cox models were used to assess genotype-specific cumulative incidence and HRs, respectively. HPV 6, 11, 16, and 18 seroprevalence was 8.1%, 13.9%, 12.7%, and 10.8%, respectively. Significantly higher rates of incident infections were observed for HPV 16 among baseline-seropositive men [adjusted HR, 1.37; 95% confidence interval (CI), 1.01-1.86], with similar but nonsignificant HRs for 6-month persistent infections. Risk of persistent HPV 18 infection was significantly lower among seropositive men in the unadjusted model (HR, 0.22; 95% CI, 0.06-0.91), but not in the adjusted model (HR, 0.19; 95% CI, 0.03-1.37). Incident and 6-month persistent infections for HPV 6 and 11 did not differ by baseline serostatus. Baseline serostatus among men was not associated with a reduction in subsequent incident genital HPV 6, 11, and 16 infections. However, protection against persistent HPV18 infections was observed in unadjusted models. Our research suggests a need of further studies to examine the potentially protective effects of naturally induced HPV18 antibodies in men. Cancer Res; 76(20); 6066-75. ©2016 AACR.

Human Papillomavirus (HPV) L1 Serum Antibodies and the Risk of Subsequent Oral HPV Acquisition in Men: The HIM Study.

The role of antibody-mediated immunity in preventing newly acquired oral human papillomavirus (HPV) is not well understood. Among 1618 men participating in the HPV Infection in Men (HIM) Study, we evaluated oral rinses for HPV DNA and baseline sera for HPV-6, -11, -16, and -18 L1 antibodies. Thirty percent of men (486) were seropositive for ≥1 HPV type, and 25 men developed incident oral HPV infection (HPV-6 was detected in 7, HPV-11 in 0, HPV-16 in 17, and HPV-18 in 1). Cox models revealed that men with circulating antibodies to HPV-6, -11, -16, or -18 were not less likely to acquire type-specific oral HPV than men without antibodies (hazard ratio for the risk of acquiring HPV-6, -11, -16, or -18, 1.63; 95% confidence interval, .56-4.76).

Salivary secretory leukocyte protease inhibitor (SLPI) and head and neck cancer: The Cancer Prevention Study II Nutrition Cohort.

OBJECTIVES: Secretory leukocyte protease inhibitor (SLPI) is an innate-immunity protein displaying antimicrobial and anti-inflammatory properties that is found in high concentrations in saliva. The role of extracellular salivary SLPI in head and neck squamous cell carcinoma (HNSCC) remains unclear. Thus, we aimed to evaluate the association between SLPI and HNSCC risk in the Cancer Prevention Study II Nutrition Cohort. MATERIALS AND METHODS: Among 53,180 men and women with no history of cancer who provided an oral rinse between 2001 and 2002, 60 were subsequently diagnosed with incident HNSCC between specimen collection and June 2009. In this nested case-control study, archived oral supernatants were evaluated using the Human SLPI Quantikine ELISA Kit for all 60 cases and 180 controls individually matched on gender, race, date of birth, and date of oral rinse collection. Conditional logistic regression was used to estimate HNSCC risk. RESULTS: Overall, pre-diagnostic salivary SLPI was associated with a non-statistically significant higher risk of HNSCC (OR=1.6, 95% CI=0.9-3.0). Among never smokers, high SLPI was associated with a non-statistically significant lower risk (OR=0.5, 95% CI=0.1-1.9), whereas among ever smokers, high SLPI was associated with a statistically significant higher risk (OR=2.1, 95% CI=1.0-4.3) of HNSCC, compared to low SLPI. CONCLUSION: While results from this study suggest that higher concentrations of salivary SLPI might increase the risk of HNSCC among ever smokers, more research is needed to verify these findings and define the mechanisms by which SLPI and smoking influence the etiology of HNSCC.

Cervical HPV natural history among young Western Cape, South African women: The randomized control EVRI Trial.

OBJECTIVE: The objective of this analysis was to assess human papillomavirus (HPV) infection persistence and incidence 7-months post-enrollment by HPV vaccine study arm (vaccine or placebo). METHODS: HIV-negative, sexually active women aged 16-24 years in the Western Cape, South Africa, were enrolled in the EVRI Trial and were randomized to receive 4-valent HPV vaccine or placebo. Cervical specimens were collected at enrollment and at the 7-month visit and were genotyped for HPV. HPV prevalence, persistence, and incidence were calculated. Prevalence ratios and odds ratios were calculated to assess factors associated with a prevalent and incident HPV infection. RESULTS: HPV incidence rates were marginally higher for the placebo group (n = 163) compared to the vaccine group (n = 169). A large proportion of the prevalent high-risk (HR-HPV) HPV types (49%) persisted over the 7-month period in both arms. Prevalent HR-HPV infection was significantly associated with a prevalent gonorrhea infection and detection of Herpes simplex type 2 antibodies. Incident HR-HPV infection was significantly associated with abnormal cervical cytology at enrollment and younger age. CONCLUSIONS: Women living in geographic areas, such as southern Africa, at high-risk for HPV need to receive HPV vaccination at a very young age to maximally prevent infection and subsequent disease.

Seroconversion Following Anal and Genital HPV Infection in Men: The HIM Study.

BACKGROUND: Protection from naturally acquired human papillomavirus (HPV) antibodies may influence HPV infection across the lifespan. This study describes seroconversion rates following genital, anal, and oral HPV 6/11/16/18 infections in men and examines differences by HPV type and anatomic site. METHODS: Men with HPV 6/11/16/18 infections who were seronegative for those genotypes at the time of DNA detection were selected from the HPV Infection in Men (HIM) Study. Sera specimens collected ≤36 months after detection were analyzed for HPV 6/11/16/18 antibodies using a virus-like particle-based ELISA. Time to seroconversion was separately assessed for each anatomic site, stratified by HPV type. RESULTS: Seroconversion to ≥1 HPV type (6/11/16/18) in this sub-cohort (N=384) varied by anatomic site, with 6.3, 18.9, and 0.0% seroconverting following anal, genital, and oral HPV infection, respectively. Regardless of anatomic site, seroconversion was highest for HPV 6 (19.3%). Overall, seroconversion was highest following anal HPV 6 infection (69.2%). HPV persistence was the only factor found to influence seroconversion. CONCLUSIONS: Low seroconversion rates following HPV infection leave men susceptible to recurrent infections that can progress to HPV-related cancers. This emphasizes the need for HPV vaccination in men to ensure immune protection against new HPV infections and subsequent disease.

Immunogenicity and safety of Gardasil among mid-adult aged men (27-45 years)--The MAM Study.

BACKGROUND: The quadrivalent (types 6/11/16/18) human papillomavirus (HPV) vaccine, Gardasil, has demonstrated efficacy against persistent HPV infection and associated anogenital disease in males. The goal of this Phase II trial was to establish the immunogenicity and safety of Gardasil among mid-adult men ages 27-45 years. METHODS: One hundred and fifty men from Tampa, FL, US, and Cuernavaca, Mexico who met eligibility criteria (male, 27-45 years old, completed four years of follow-up in the HPV Infection in Men (HIM) natural history study) were enrolled. Subjects completed four visits over seven months, with Gardasil administered at Day 1 and Months 2 and 6. Sera were collected at Day 1 (pre-vaccination) and Month 7 (one month post-dose three). Anti-HPV6, 11, 16, and 18 IgG levels were determined by competitive Luminex immunoassay. FINDINGS: 100% of men seroconverted to each of the four HPV vaccine components, and the vaccine was generally well-tolerated. Antibody responses to vaccine did not differ by age group or sexual orientation, regardless of HPV type, and were significantly higher at Month 7 among men who entered the trial seropositive for HPV 6 or 11. INTERPRETATION: The immune response to HPV vaccination in men ages 27-45 was comparable to that observed in younger men, in whom clinical efficacy was demonstrated. Further trials to assess the efficacy of HPV vaccines to prevent persistent HPV infections in mid-adult men are needed. FUNDING: Merck & Co. Inc. was the main sponsor of this trial (IISP39256) and provided the study product.

Alcohol consumption and prevalence of human papillomavirus (HPV) infection among US men in the HPV in Men (HIM) study.

OBJECTIVES: Moderate alcohol consumption can impair host defence against viral infections. The objective of this cross-sectional analysis was to assess the association between alcohol intake and prevalent human papillomavirus (HPV) infection among US men enrolled in the HPV in Men (HIM) study using quantitative alcohol intake measured from a Food Frequency Questionnaire. METHODS: The HIM study is a prospective, multinational study of the natural history of HPV infection. For this report, we restricted our analyses to men from the US cohort (N = 1313). Samples from the corona of glans penis, penile shaft and scrotum were combined for HPV DNA testing. Self-reported alcohol intake was quantified by grams of alcohol intake per day. Multivariable prevalence ratios (mPRs) were used to assess the association between alcohol intake and HPV infections. RESULTS: Prevalent infections were significantly higher among men in the highest quartile of alcohol intake and multivariable models revealed that the highest quartile of alcohol intake was associated with significantly increased risks for any (mPR = 1.13; 95% CI 1.00 to 1.27) HPV types and oncogenic (mPR = 1.35; 95% CI 1.08 to 1.68) HPV types. The fourth quartile of alcohol intake was associated with elevated risks for prevalent HPV infection across all strata of number of sexual partners and among never-smokers and current smokers, but not among former smokers. CONCLUSIONS: These results demonstrate that high intake of alcohol is associated with an increased risk for prevalent HPV infections among men. The biological role that alcohol plays in genital HPV infection remains understudied and limited epidemiological data exist, especially among men.