The Strong Protective Effect of Circumcision against Cancer of the Penis

Male circumcision protects against cancer of the penis, the invasive form of which is a devastating disease confined almost exclusively to uncircumcised men. Major etiological factors are phimosis, balanitis, and high-risk types of human papillomavirus (HPV), which are more prevalent in the glans penis and coronal sulcus covered by the foreskin, as well as on the penile shaft, of uncircumcised men. Circumcised men clear HPV infections more quickly. Phimosis (a constricted foreskin opening impeding the passage of urine) is confined to uncircumcised men, in whom balanitis (affecting 10%) is more common than in circumcised men. Each is strongly associated with risk of penile cancer. These findings have led to calls for promotion of male circumcision, especially in infancy, to help reduce the global burden of penile cancer. Even more relevant globally is protection from cervical cancer, which is 10-times more common, being much higher in women with uncircumcised male partners. Male circumcision also provides indirect protection against various other infections in women, along with direct protection for men from a number of genital tract infections, including HIV. Given that adverse consequences of medical male circumcision, especially when performed in infancy, are rare, this simple prophylactic procedure should be promoted

Smoking and passive smoking in cervical cancer risk: pooled analysis of couples from the IARC multicentric case-control studies.

BACKGROUND: The independent role of tobacco smoking in invasive cervical cancer (ICC) has been established. We evaluated the potential impact of passive smoking (PS). METHODS: A pooled analysis of 1,919 couples enrolled in one of seven case-control studies involving cervical carcinoma in situ (CIS) or ICC was investigated. Information on smoking and sexual behavior was collected from interviews. Specimens were taken from the cervix and penis for human papillomavirus (HPV) DNA testing. Three PS risk models were constructed with all couples, couples with monogamous women, and couples with lifetime nonsmoking monogamous women. For the third model, the analysis considered potential misclassification of smoking status and was restricted to the risk period for which the woman was exposed to both HPV, a necessary cause of ICC, and PS. Multivariable unconditional logistic regression was used to estimate associations between CIS or ICC and PS. RESULTS: An increased risk was found among couples with both ever smoking men and women (OR = 2.26; 95% CI: 1.40-3.64). No statistically increased risk of CIS was found with PS in the models analyzed. Similar significant increased risks of ICC with PS was found among all couples (OR = 1.57; 95% CI: 1.15-2.15) and couples with monogamous women (OR = 1.55; 95% CI: 1.07-2.23) but not among lifetime nonsmoking monogamous women married to ever smoking men. CONCLUSION: PS could not be detected as an independent risk factor of ICC in the absence of active smoking. IMPACT: The combined effects of exposure to active and PS suggest its potential adverse role in cervical carcinogenesis

Human Papillomavirus type distribution in invasive cervical cancer in Uganda

<p>Abstract</p> <p>Background</p> <p>We conducted a study aiming to describe Human Papillomavirus (HPV) type distribution in invasive cervical carcinoma in Uganda.</p> <p>Methods</p> <p>191 archival cervical carcinoma samples diagnosed in the Department of Pathology, Makerere University in Kampala between 1968 and 1992 were analysed using a sensitive PCR-Reverse Hybridization Line Probe Assay.</p> <p>Results</p> <p>Out of the 186 cases of confirmed invasive cervical cancer in the study paraffin blocks, 114 were positive for HPV DNA. Specific HPV genotypes were identifiable in 109 cases: HPV 16, 18, 31, 35, 39, 44, 45, 51, 52 and 70. These occurred as single infections in 105 cases (96.3%) and as multiple infections in 4 cases (3.7%). HPV 16 or 18 accounted for 80% (84/105) of cases with single infection.</p> <p>Conclusion</p> <p>The results of this study confirm the role of HPV 16 and 18 in cervical cancer pathogenesis in the Ugandan population. The results suggest that the currently available HPV vaccines against HPV 16 and 18 could possibly prevent the majority of invasive cervical cancers in Uganda.</p

Alcohol Drinking in Never Users of Tobacco, Cigarette Smoking in Never Drinkers, and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Background At least 75% of head and neck cancers are attributable to a combination of cigarette smoking and alcohol drinking. A precise understanding of the independent association of each of these factors in the absence of the other with the risk of head and neck cancer is needed to elucidate mechanisms of head and neck carcinogenesis and to assess the efficacy of interventions aimed at controlling either risk factor. Methods We examined the extent to which head and neck cancer is associated with cigarette smoking among never drinkers and with alcohol drinking among never users of tobacco. We pooled individual-level data from 15 case-control studies that included 10244 head and neck cancer case subjects and 15227 control subjects, of whom 1072 case subjects and 5775 control subjects were never users of tobacco and 1598 case subjects and 4051 control subjects were never drinkers of alcohol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. All statistical tests were two-sided. Results Among never drinkers, cigarette smoking was associated with an increased risk of head and neck cancer (OR for ever versus never smoking = 2.13, 95% CI = 1.52 to 2.98), and there were clear dose-response relationships for the frequency, duration, and number of pack-years of cigarette smoking. Approximately 24% (95% CI = 16% to 31%) of head and neck cancer cases among nondrinkers in this study would have been prevented if these individuals had not smoked cigarettes. Among never users of tobacco, alcohol consumption was associated with an increased risk of head and neck cancer only when alcohol was consumed at high frequency (OR for three or more drinks per day versus never drinking = 2.04, 95% CI = 1.29 to 3.21). The association with high-frequency alcohol intake was limited to cancers of the oropharynx/hypopharynx and larynx. Conclusions Our results represent the most precise estimates available of the independent association of each of the two main risk factors of head and neck cancer, and they exemplify the strengths of large-scale consortia in cancer epidemiolog

Male circumcision and prevalence of genital human papillomavirus infection in men : a multinational study

Background: Accumulated evidence from epidemiological studies and more recently from randomized controlled trials suggests that male circumcision (MC) may substantially protect against genital HPV infection in men. The purpose of this study was to assess the association between MC and genital HPV infection in men in a large multinational study. Methods: A total of 4072 healthy men ages 18-70 years were enrolled in a study conducted in Brazil, Mexico, and the United States. Enrollment samples combining exfoliated cells from the coronal sulcus, glans penis, shaft, and scrotum were analyzed for the presence and genotyping of HPV DNA by PCR and linear array methods. Prevalence ratios (PR) were used to estimate associations between MC and HPV detection adjusting for potential confounders. Results: MC was not associated with overall prevalence of any HPV, oncogenic HPV types or unclassified HPV types. However, MC was negatively associated with non-oncogenic HPV infections (PR 0.85, 95% confident interval: 0.76-0.95), in particular for HPV types 11, 40, 61, 71, and 81. HPV 16, 51, 62, and 84 were the most frequently identified genotypes regardless of MC status. Conclusions: This study shows no overall association between MC and genital HPV infections in men, except for certain non-oncogenic HPV types for which a weak association was found. However, the lack of association with MC might be due to the lack of anatomic site specific HPV data, for example the glans penis, the area expected to be most likely protected by MC

Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

Background Head and neck cancer (HNC) risk is elevated among lean people and reduced among overweight or obese people in some studies; however, it is unknown whether these associations differ for certain subgroups or are influenced by residual confounding from the effects of alcohol and tobacco use or by other sources of biases. Methods We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. Results Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) ≤18.5 kg/m2 (2.13, 1.75-2.58) and reduced for BMI >25.0-30.0 kg/m2 (0.52, 0.44-0.60) and BMI ≥30 kg/m2 (0.43, 0.33-0.57), compared with BMI >18.5-25.0 kg/m2. These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI ≤18.5 kg/m2 was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m2 was present only in smokers and drinkers. Conclusions In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studie

Human papillomavirus 16 is an aetiological factor of scrotal cancer

Background: Squamous cell scrotal carcinoma (SCSC) is an infrequent skin cancer associated historically with occupational carcinogens. Human papillomavirus (HPV) DNA has been associated with SCSC but there is no definitive proof of its oncogenic role. Methods: Human papillomavirus-DNA and -E6*I mRNA were analysed in six invasive histologically typed SCSC. LCM-PCR was used to localise HPV DNA to tumour cells. P16(INK4a)and p53 expression were studied by immunohistochemistry. Results: In three warty or basaloid SCSC HPV16-DNA and E6*I-mRNA were detected. LCM-PCR confirmed HPV16 was in p16(INK4a)-positive malignant cells. However, of three usual-type SCSC, all were HPV-negative and two expressed p53 protein but not p16(INK4a). Conclusions: Human papillomavirus 16 was present in tumour cells and oncogenically active in basaloid and warty SCSC, whereas usual SCSC was HPV-negative and showed immunostaining, suggesting p53 mutation. The dual pathways of oncogenesis and relation between histological type of SCSC and HPV are similar to that in penile cancers

Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk

Background Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers. Methods We pooled individual-level data from case-control studies in the International Head and Neck Cancer Epidemiology Consortium. Data were available from 13 studies on drinking cessation (9167 cases and 12 593 controls), and from 17 studies on smoking cessation (12 040 cases and 16 884 controls). We estimated the effect of quitting smoking and drinking on the risk of head and neck cancer and its subsites, by calculating odds ratios (ORs) using logistic regression models. Results Quitting tobacco smoking for 1-4 years resulted in a head and neck cancer risk reduction [OR 0.70, confidence interval (CI) 0.61-0.81 compared with current smoking], with the risk reduction due to smoking cessation after ≥20 years (OR 0.23, CI 0.18-0.31), reaching the level of never smokers. For alcohol use, a beneficial effect on the risk of head and neck cancer was only observed after ≥20 years of quitting (OR 0.60, CI 0.40-0.89 compared with current drinking), reaching the level of never drinkers. Conclusions Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cance

Risk of first cervical HPV infection and pre-cancerous lesions after onset of sexual activity : analysis of women in the control arm of the randomized, controlled PATRICIA trial

Peer reviewe

Natural History of Progression of HPV Infection to Cervical Lesion or Clearance: Analysis of the Control Arm of the Large, Randomised PATRICIA Study

Peer reviewe