Gabriella M. Anic

Incidence and clearance of genital human papillomavirus infection in men (HIM): a cohort study

BACKGROUND Human papillomaviruses (HPVs) cause genital warts and cancers in men. The natural history of HPV infection in men is largely unknown, and that information is needed to inform prevention strategies. The goal in this study was to estimate incidence and clearance of type-specific genital HPV infection in men, and to assess the associated factors. METHODS Men (aged 18-70 years), residing in Brazil, Mexico, and the USA, who were HIV negative and reported no history of cancer were recruited from the general population, universities, and organised health-care systems. They were assessed every 6 months for a median follow-up of 27·5 months (18·0-31·2). Specimens from the coronal sulcus, glans penis, shaft, and scrotum were obtained for the assessment of the status of HPV genotypes. FINDINGS In 1159 men, the incidence of a new genital HPV infection was 38·4 per 1000 person months (95% CI 34·3-43·0). Oncogenic HPV infection was significantly associated with having a high number of lifetime female sexual partners (hazard ratio 2·40, 1·38-4·18, for at least 50 partners vs not more than one partner), and number of male anal-sexual partners (2·57, 1·46-4·49, for at least three male partners vs no recent partners). Median duration of HPV infection was 7·52 months (6·80-8·61) for any HPV and 12·19 months (7·16-18·17) for HPV 16. Clearance of oncogenic HPV infection decreased in men with a high number of lifetime female partners (0·49, 0·31-0·76, for at least 50 female partners vs not more than one partner), and in men in Brazil (0·71, 0·56-0·91) and Mexico (0·73, 0·57-0·94) compared with the USA. Clearance of oncogenic HPV was more rapid with increasing age (1·02, 1·01-1·03). INTERPRETATION The data from this study are useful for the development of realistic cost-effectiveness models for male HPV vaccination internationally. FUNDING National Cancer Institute.

Epidemiology and pathology of HPV disease in males

It is currently recognized that besides the significant impact of human papillomavirus (HPV) infection in females, HPV causes substantial disease in men as well. Genital warts are a common manifestation of male infection with HPV. Genital warts are highly infectious and approximately 65% of people who have sex with an infected partner will develop warts themselves. More than 90% of genital warts are caused by non-oncogenic HPV types 6 and 11. In addition, recurrent respiratory papillomatosis is a rare disease most often associated with HPV types 6 and 11. Several cancers of the anogenital tract and upper aero-digestive tract, and their precursor lesions in men are now understood to be caused by infection with sexually transmitted HPV. For example, there is increasing incidence of anal cancer in western countries; however, there are limited data on its primary cause, anal canal HPV infection. Genital HPV infection is very common in men with an ongoing international study estimating a prevalence of 65.2% in asymptomatic males aged 18-70 years. Lifetime number of sexual partners was the most significant risk factor for the acquisition of HPV infection (P<0.05), and circumcision has been associated with reduced detection of HPV infection in men. HPV infections may be less likely to persist in men than in women. In men, the median time to clearance of any HPV infection was 5.9 months, with 75% of infections clearing within 12 months. More data are needed to better understand the natural history of HPV infection. Although the quadrivalent HPV vaccine has been shown to be effective and safe in men, low awareness of HPV in males may be a barrier to its use for the prevention of HPV infection.

Genital HPV infection and related lesions in men

Human papillomavirus (HPV) is highly prevalent in men and there is an interest in further understanding the relationship between HPV infection and disease in men, including the development of genital warts, penile intraepithelial neoplasia and invasive penile carcinomas. Genital warts are caused by HPV 6/11 and are the most common clinical manifestation of HPV in men. Though they are benign and not associated with mortality, they are a source of psychosocial distress and physical discomfort. HPV infection can also develop into invasive penile carcinoma which is associated with morbidity and mortality. Approximately 40% of invasive penile carcinomas are attributable to HPV with HPV 16, 18, and 6/11 being the genotypes most commonly detected in penile tumors. Penile carcinomas of the basaloid and warty histologic subtypes are most likely to test positive for HPV. In addition to HPV infection, the risk factors most strongly associated with penile cancer are lack of neonatal circumcision, phimosis (the inability of uncircumcised men to fully retract the foreskin), and anogenital warts. Male vaccination with the quadrivalent HPV vaccine that protects against HPV 6/11/16/18 has been shown to significantly reduce HPV-associated anogenital infection and disease in men. If the quadrivalent vaccine is successfully disseminated to large segments of the young male population, there is the potential for substantial reduction in genital HPV infection and related lesions in men.

Sleep duration and obesity in a population-based study

BACKGROUND Previous studies have demonstrated an association between sleep duration and obesity, but few population-based studies have examined the association. We examined the relationship between recent and usual lifetime sleep duration with the odds of obesity in 5549 women that participated in a population-based telephone survey. METHODS The structured telephone interview included questions on usual sleep duration in adult life and the recent past, as well as height and weight and other demographic and lifestyle characteristics. We examined odds of overweight (BMI: 25-29.9 kg/m(2)), obesity (BMI: 30-39.9 kg/m(2)) and extreme obesity (BMI: 40 kg/m(2)) according to reported sleep duration. RESULTS Compared to women who slept 7-7.9h per night, women who slept an average of <6h per night in the recent past had significantly greater odds of obesity (Odds Ratio [OR]: 1.89; 95% Confidence Interval [CI]: 1.45-2.47) and extreme obesity (OR: 3.12; CI: 1.70-5.75), adjusting for potential confounding factors. Weaker associations were noted for short lifetime sleep duration. Current short sleep (<7h) was associated with greater odds of obesity (30 kg/m(2)) in those reporting less than 7h (OR: 1.59; 95% CI: 0.93-2.78) and in those reporting 8 or more hours (OR: 1.75; 95% CI: 1.33-2.32) of sleep throughout adult life. CONCLUSIONS Current short sleepers were more likely to be obese regardless of their usual sleep duration earlier in life. These findings do not support the hypothesis that sleep duration is a causal factor in obesity.

Incidence and Human Papillomavirus (HPV) Type Distribution of Genital Warts in a Multinational Cohort of Men: The HPV in Men Study

BACKGROUND Data on the natural history of human papillomavirus (HPV)-related genital warts (GWs) in men are sparse. We described the distribution of HPV types in incident GWs and estimated GW incidence and time from type-specific incident HPV infections to GW detection in a multinational cohort of men aged 18-70 years. METHODS Participants included 2487 men examined for GWs and tested for HPV every 6 months and followed up for a median of 17.9 months. Samples were taken from 112 men with incident GWs to test for HPV DNA by polymerase chain reaction. RESULTS Incidence of GWs was 2.35 cases per 1000 person-years, with highest incidence among men aged 18-30 years (3.43 cases per 1000 person-years). HPV 6 (43.8%), HPV 11 (10.7%), and HPV 16 (9.8%) were the genotypes most commonly detected in GWs. The 24-month cumulative incidence of GWs among men with incident HPV 6/11 infections was 14.6% (95% confidence interval [CI], 7.5%-21.1%). Median time to GW detection was 17.1 months (95% CI, 12.4-19.3 months), with shortest time to detection among men with incident infections with HPV 6/11 only (6.2 months; 95% CI, 5.6-24.2 months). CONCLUSIONS HPV 6/11 plays an important role in GW development, with the highest incidence and shortest time to detection among men with incident HPV 6/11 infection.

Telomere length and risk of melanoma, squamous cell carcinoma, and basal cell carcinoma.

BACKGROUND Telomeres help maintain chromosomal structure and may influence tumorigenesis. We examined the association between telomere length and skin cancer in a clinic-based case-control study of 198 melanoma cases, 136 squamous cell carcinoma (SCC) cases, 185 basal cell carcinoma (BCC) cases, and 372 healthy controls. METHODS Cases were histologically confirmed patients treated at the Moffitt Cancer Center and University of South Florida Dermatology Clinic in Tampa, FL. Controls self-reported no history of cancer and underwent a skin cancer screening exam at study enrollment to rule out the presence of skin cancer. Quantitative real time PCR was used to measure telomere length in peripheral blood samples. RESULTS Melanoma patients had longer telomeres than controls (odds ratio (OR)=3.75; 95% confidence interval (CI): 2.02-6.94 for highest versus lowest tertile) (P for trend=<0.0001). In contrast, longer telomere length was significantly inversely associated with SCC (OR=0.01; 95% CI: 0.00-0.05 for highest versus lowest tertile) (P for trend=<0.0001) and BCC (OR=0.10; 95% CI: 0.06-0.19 for highest versus lowest tertile) (P for trend=<0.0001). CONCLUSION Telomere length may be involved in the development of skin cancer, although the effect on cancer risk differs for melanoma and non-melanoma carcinomas. Our findings suggest that long telomere length is positively associated with melanoma while inversely associated with SCC and BCC.

Tea Consumption and Risk of Breast Cancer

Objective: The purpose of our study was to examine the association of regular tea consumption with the risk of breast cancer in a large population-based case-control study from the United States. Methods: Five thousand and eighty-two women with incident breast cancer between the ages of 20 and 74 years old from population-based cancer registries in Wisconsin, Massachusetts, and New Hampshire and 4,501 age-matched controls from lists of licensed drivers and Medicare beneficiaries completed a structured telephone interview that included information on usual tea consumption 5 years prior to the interview and other breast cancer risk factors. Logistic regression was used to obtain covariate-adjusted odds ratios and 95% confidence intervals associated with quantities of tea consumed. Results: Tea consumption was not related to breast cancer risk overall (P for trend = 0.18). However, when stratified by age, an inverse association was observed among women less than 50 years: those consuming three or more cups per day had a 37% reduced breast cancer risk when compared with women reporting no tea consumption (age and study site–adjusted odds ratios, 0.63; 95% confidence intervals, 0.44-0.89; P = 0.01) with a significant test for trend (P = 0.01). The inverse association noted among younger women was consistent for in situ and invasive breast cancer, and for ductal and lobular breast cancer. All results were unchanged after adjustment for established risk factors. Conclusion: We observed evidence to support a potential beneficial influence for breast cancer associated with moderate levels of tea consumption (three or more cups per day) among younger women. Further research is needed to confirm this association. (Cancer Epidemiol Biomarkers Prev 2009;18(1):341–5)

Childbearing Recency and Modifiers of Premenopausal Breast Cancer Risk

The purpose of this study was to examine the risk of premenopausal breast cancer for women in relation to childbearing recency and whether this association differs by breast-feeding history and/or the amount of weight gained during pregnancy. This analysis was based on data from a population-based case-control study composed of 1,706 incident cases of invasive breast cancer and 1,756 population controls from Wisconsin, New Hampshire, and Massachusetts. In a telephone interview conducted from 1996 to 2001, information was gathered on established breast cancer risk factors, as well as reproductive history, including amount of weight gained during the last full-term pregnancy and whether the child was breast-fed. Unconditional logistic regression was used to estimate odds ratios and Wald 95% confidence intervals for the risk of breast cancer. When compared with nulliparous women, women that had given birth within the past 5 years before breast cancer diagnosis in the cases or a comparable period in controls had a nonsignificant 35% increased risk of invasive breast cancer (odds ratio, 1.35; 95% confidence interval, 0.90-2.04), adjusting for age and known breast cancer risk factors (Ptrend = 0.14). We did not find a significant interaction with breast-feeding (Pinteraction = 0.30) or pregnancy weight gain (Pinteraction = 0.09). (Cancer Epidemiol Biomarkers Prev 2008;17(11):3284–7)

Risk Factors for Incident Condyloma in a Multinational Cohort of Men: The HIM Study

Identifying factors associated with condyloma are necessary for prevention efforts. Risk factors for incident condyloma were examined in a cohort of 2487 men from the United States, Brazil, and Mexico and were followed up every 6 months (median, 17.9 months). Factors strongly associated with condyloma were incident infection with human papillomavirus (HPV) types 6 and 11 (hazard ratio [HR], 12.42 [95% confidence interval {CI}, 3.78-40.77]), age (HR, 0.43 [95% CI, .26-.77]; 45-70 vs 18-30 years), high lifetime number of female partners (HR, 5.69 [95% CI, 1.80-17.97]; ≥21 vs 0 partners), and number of male partners (HR, 4.53 [95% CI, 1.68-12.20]; ≥3 vs 0 partners). The results suggest that HPV types 6 and 11 and recent sexual behavior are strongly associated with incident condyloma.

An inherited variant in the gene coding for vitamin D-binding protein and survival from cutaneous melanoma: a BioGenoMEL study

An association between low serum vitamin D levels and poorer melanoma survival has been reported. We have studied inheritance of a polymorphism of the GC gene, rs2282679, coding for the vitamin D‐binding protein, which is associated with lower serum levels of vitamin D, in a meta‐analysis of 3137 melanoma patients. The aim was to investigate evidence for a causal relationship between vitamin D and outcome (Mendelian randomization). The variant was not associated with reduced overall survival (OS) in the UK cohort, per‐allele hazard ratio (HR) for death 1.23 (95% confidence interval (CI) 0.93, 1.64). In the smaller cohorts, HR in OS analysis was 1.07 (95% CI 0.88, 1.3) and for all cohorts combined, HR for OS was 1.09 (95% CI 0.93, 1.29). There was evidence of increased melanoma‐specific deaths in the seven cohorts for which these data were available. The lack of unequivocal findings despite the large sample size illustrates the difficulties of implementing Mendelian randomization.