Objectives To investigate the role of human papillomavirus (HPV) in the development of cervical neoplasia in women with no previous cervical cytological abnormalities; whether the presence of virus DNA predicts development of squamous intraepithelial lesion; and whether the risk of incident squamous intraepithelial lesions differs with repeated detection of the same HPV type versus repeated detection of different types. Design Population based prospective cohort study. Setting General population in Copenhagen, Denmark. Participants 10 758 women aged 20-29 years followed up for development of cervical cytological abnormalities; 370 incident cases were detected (40 with atypical squamous cells of undetermined significance, 165 with low grade squamous intraepithelial lesions, 165 with high grade squamous intraepithelial lesions). Main outcome measures Results of cervical smear tests and cervical swabs at enrolment and at the second examination about two years later. Results Compared with women who were negative for human papillomavirus at enrolment, those with positive results had a significantly increased risk at follow up of having atypical cells (odds ratio 3.2, 95% confidence interval 1.3 to 7.9), low grade lesions (7.5, 4.8 to 11.7), or high grade lesions (25.8, 15.3 to 43.6). Similarly, women who were positive for HPV at the second examination had a strongly increased risk of low (34.3, 17.6 to 67.0) and high grade lesions (60.7, 25.5 to 144.0). For high grade lesions the risk was strongly increased if the same virus type was present at both examinations (813.0, 168.2 to 3229.2). Conclusions Infection with human papillomavirus precedes the development of low and high grade squamous intraepithelial lesions. For high grade lesions the risk is greatest in women positive for the same type of HPV on repeated testing.

Objectives: Genital infection with certain types of human papillomavirus (HPV) is the most important risk factor for cervical cancer. The male sexual partner is supposed to be the vector of the infection. However, the knowledge of risk factors for genital HPV DNA in men is limited. The objective of this paper is to study the risk factors for HPV infection in men and to compare them with those found in women, including the study of whether there are different risk profiles for oncogenic and non-oncogenic HPV types. Methods: From a sexually transmitted diseases (STD) clinic in Denmark, 216 men were consecutively included. A personal interview was done and material for genital HPV DNA detection was obtained with swabs. HPV DNA was detected by polymerase chain reaction (PCR). Odds ratios (OR) for HPV as well as for oncogenic and non-oncogenic types separately were computed with a 95% confidence interval (CI) by means of unconditional multiple logistic regresssion. Results:The most important predictors of any HPV were lifetime number of sex partners (OR = 4.3; 95% CI 1.4 to 13.1 for 25-39 v 1-9 partners), young age, and being uncircumcised. The most important risk factor for oncogenic HPV types was lifetime number of partners, whereas number of partners in the past year and ever having genital warts were risk factors for the non-oncogenic HPV types. Young age predicted risk of both oncogenic and non-oncogenic HPV types. Conclusions: Most risk factors for HPV DNA detection in men resemble those found in women. As in women, the risk factor profile for the oncogenic HPV types was different from that of the non-oncogenic HPV types. G enital infection with certain human papillomavirus (HPV) types, especially HPV 16, has consistently been reported as the most important risk factor for cervical neoplasia 1 and the male sexual partner has been implicated as the vector of the virus.2 Variables such as age, proximity to first intercourse, and number of male sexual partners (during lifetime and more recently) have consistently been found to predict risk of genital HPV detection in women.3-7 Furthermore, in women, there seems to be different profiles of risk factors for acquiring oncogenic HPV types and non-oncogenic HPV types. [8][9][10][11] In men, however, only few studies have focused on risk factors for genital HPV DNA detection and they have shown association to variables related to sexual behavior such as multiple sexual partners, previous sexually transmitted diseases (STDs), and non-use of condoms.12 13 Studies of risk factors in men for genital infection with oncogenic HPV types and non-oncogenic HPV types as separate groups have not been done. To improve the understanding of the natural history of genital HPV infection it is important to know if there is gender related differences in the determinants for the infection. Therefore, the objective of this study was to determine the risk factors for HPV infection in men and to compare them with those previously described in women. Moreover, it was the goal to compare the r...

Background: Few epidemiologic studies have examined the association between fertility drugs and breast cancer risk, and results have been contradicting. Using data from the largest cohort of infertile women to date, the aim of this study was to examine the effects of fertility drugs on breast cancer risk overall and according to histologic subtypes. Method: A cohort of 54,362 women with infertility problems referred to all Danish fertility clinics between 1963 and 1998 was established. A detailed data collection, including information of type and amount of treatment, was conducted. We used case-cohort techniques to calculate rate ratios (RR) of breast cancer associated with use of five groups of fertility drugs, after adjustment for parity status. Results: Three hundred thirty-one invasive breast cancers were identified in the cohort during follow-up through 1998. Analyses within cohort showed no overall increased breast

Seroreactivity to human papillomavirus type 16 (HPV-16) virus-like particles (VLPs) in men attending clinics for sexually transmitted diseases (STDs) in Denmark (n = 219) and Greenland (n = 88) was compared with seroreactivity in women attending the same clinics and was furthermore related to epidemiologic variables and concurrent HPV DNA detection. Risk factors for male seropositivity in Denmark were lifetime number of sex partners, a history of STDs, and sexual preference and in Greenland were ever having had syphilis and years at school. Although men reported significantly more sex partners, the mean seroreactivity was significantly lower in men than in women: 0.50 and 0.75, respectively, in Denmark and 0.53 and 0.86 in Greenland (P = .0001). Male seropositivity was not correlated with concurrent HPV DNA detection, but only 15 Danish and 6 Greenlandic men had HPV-16 DNA. Presence of HPV-16 VLP antibodies appears to be a biomarker for exposure to genital HPVs in men but is less sensitive than in women.

In spite of the success of cervical cytology as a cancerscreening tool, it has important limitations, and human papillomavirus (HPV) testing may be valuable in future screening. The majority of women in screened populations, who test HPV positive, will have a concurrent normal smear, and we need more information about the risk for subsequent high-grade cervical lesions in these women. We examined 8,656 younger women (22-32 years old) and 1,578 older women (40-50 years old) who were followed for development of cervical neoplasia (cytology and/or histology) through the Danish Pathology Data Bank. We estimated the proportion of women developing cervical lesions of different types before a given time point as a function of time. Among women with normal cytology and positive high-risk Hybrid Capture 2 (HC2) test, 17.7% and 24.5% of younger and older women, respectively, had a subsequent abnormal Pap smear within 5 years. The risk of CIN3 or cancer within 10 years among younger women with positive HC2 test was 13.6% (10.9-16.2) and 21.2% (2.7-36.1) among older women. An analysis among younger women also being HC2-positive 2 years before baseline showed a subsequent 10-year risk of zCIN3 of 18% (14.6-21.5). Among older women where HPV may be added to general screening, the estimated absolute risk of zCIN3 in HC2-positive women was more than 20% within 10 years. These results indicate that even a single positive HPV test in cytologically negative women is substantially predictive of high-grade CIN and suggest that HC2 testing can help stratify women into different risk categories. (Cancer Res 2006; 66(21): 10630-6)