Treatment of extramammary Paget disease of the vulva with imiquimod: a retrospective, multicenter study by the German Colposcopy Network.

BACKGROUND: Extramammary Paget disease (EMPD) is a very rare genital neoplasia associated with a high frequency of local recurrences. Surgical excision is the standard treatment, but results in mutilating procedures in patients with advanced or recurrent disease. Case reports have shown clinical responses to imiquimod in patients with EMPD, but this therapy has not been evaluated systematically. OBJECTIVE: The aim of this study was to evaluate imiquimod as local treatment of first-time and recurrent EMPD. METHODS: All cases of biopsy-proven EMPD of the vulva treated within the German Colposcopy Network or other institutions specializing in vulvar diseases in Germany were included in this retrospective analysis. RESULTS: A total of 21 women with EMPD treated with imiquimod were identified: 11 (52.4%) achieved complete response, 6 (28.6%) achieved partial response, and there were no cases of progressive disease. The dose and duration of imiquimod differed between patients. The mean duration of treatment exceeded 16 weeks in women achieving complete response. LIMITATIONS: EMPD is rare and this retrospective study is limited by the small number of patients identified. CONCLUSION: When associated cancers and invasive growth are excluded, imiquimod appears to be a useful treatment option for recurrent EMPD and may avoid extensive mutilating surgical treatment.

Young age at first intercourse and subsequent risk-taking behaviour: An epidemiological study of more than 20,000 Danish men from the general population.

AIM: First intercourse at the age of 14 years or younger is usually considered high-risk behaviour for sexually transmitted infections (STIs). It has been linked to other types of risky behaviour in women, while conflicting results have been obtained for men. The aim of the study was to estimate the prevalence of first intercourse at a young age in various birth cohorts of men and to determine any association with later risky behaviour. METHODS: We studied 22,979 randomly selected men aged 18-45 years from the Danish general male population who responded to a self-administered questionnaire. Multiple sexual partners over a lifetime, multiple new sexual partners within the past 6 months, intercourse with a commercial sex worker, having an STI, binge drinking and current smoking were considered risky behaviour. RESULTS: First intercourse at the age of 14 years or younger was more prevalent in younger (14%) than in older (10%) birth cohorts and among men with shorter schooling. Young age at sexual debut was associated with a more than twofold increase in the risks for subsequent risky behaviour. CONCLUSIONS: More than 10% of Danish men first had sex at an early age, and this was closely related to subsequent risk-taking behaviour.

Annual Papanicolaou screening for 5 years among human papillomavirus-negative women.

BACKGROUND: Primary human papilloma virus (HPV) screening is more effective than cytology in reducing the risk of cervical cancer, but screening intervals should be extended in HPV-negative women. However, some Markov models predicted that long intervals are associated with an excess risk of cervical cancer. The aim of this analysis was to estimate the real-life risks and benefits of annual Papanicolaou (Pap) screening in HPV-negative women with normal cytology. METHODS: Women with negative Hybrid Capture 2 (HC2) results and normal cytology at the time of inclusion in the Hannover HPV screening trial underwent annual Pap smears for 5 years. A subgroup was randomly selected for retesting with cytology, HC2, and colposcopy 60-68 months after recruitment. RESULTS: Of 4236 women included, 3406 had at least one Pap smear, but only 1185 attended all five annual screening visits. The proportion of women with at least one abnormal smear was 14.4% in 60 months. The probability of abnormal smears increased continuously over time. No case of ≥ CIN2+ was observed during 5 years. Of 605 women selected for subgroup analysis, 292 agreed to be retested (48.3%). The rate of high-risk HPV at 60-68 months was 3.0% (9/296). CONCLUSIONS: The long-term risk of high-grade neoplasia after an initial negative HC2 test and normal cytology result was low, while the rate of false-positive abnormal Pap smears was significant and increased constantly over time. Pap smear screening of HPV-negative women more frequently than every 5 years could be potentially harmful and seems to be of little clinical value.

Sexual risk taking behaviour: prevalence and associated factors. A population-based study of 22,000 Danish men.

BACKGROUND: Sexual habits and risky sexual behaviour strongly affect public health. Available data indicate that sexually transmitted infections are increasing in many EU countries. Changes in the epidemiology of sexually transmitted diseases across Europe are among other factors suggested to be driven by changes in sexual behaviour patterns. The purpose of our study is to assess the occurrence of risky behaviour in men aged 18-45 years from the general population. Furthermore, we aim to examine factors associated with risky sexual behaviour. METHODS: A random sample of 33,000 Danish men (18-45 years) was selected from the general population. The participants (participation-rate: 71.0%) received a self-administered questionnaire which could be returned in a paper-based version or as a web-based questionnaire. Non-respondents were subsequently asked to participate in a telephone interview with the same questions as in the paper- or web-based questionnaire. We defined risky sexual behaviour as > 8 lifetime sexual partners, ≥2 new sexual partners in the past 6 months and intercourse with a commercial sex worker. RESULTS: The Danish men reported having had sexual intercourse with a median of 8 female partners during their lifetime and 9.8% of the men have had ≥2 new sexual partners in the past 6 months. Sexual intercourse with a commercial sex worker was reported by 11.3% of the men. Furthermore, men reporting > 8 lifetime partners or ≥2 recent sex partners were more likely to have other risk taking behaviours such as early sexual debut, current smoking and regular binge drinking. A similar pattern was seen in men who had sex with a commercial sex worker. CONCLUSIONS: Our results show that a high proportion of Danish men have had sexual contact with a large number of partners, and risky sexual behaviour is closely related to other risk-taking behaviours such as smoking and binge drinking.

Human papillomavirus prevalence and type-distribution, cervical cancer screening practices and current status of vaccination implementation in Russian Federation, the Western countries of the former Soviet Union, Caucasus region and Central Asia.

Limited data are available on the burden of human papillomavirus (HPV) and its associated diseases in the Russian Federation, the Western Countries of the former Soviet Union (Belarus, Republic of Moldova, Ukraine), the Caucasus region and Central Asia (Armenia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan). Both the incidence and mortality rate of cervical cancer are higher in these countries than in most Western European countries. In this article, we review available data on HPV prevalence and type distribution in women with normal cytology, women from the general population, cervical precancerous lesions and cervical cancer, as well as data on national policies of cervical cancer screening and HPV vaccination initiatives in these countries. Based on scarce data from the 12 countries, the high-risk HPV (hrHPV) prevalence among 5226 women with normal cytology ranged from 0.0% to 48.4%. In women with low-grade cervical lesions, the hrHPV prevalence among 1062 women varied from 29.2% to 100%. HrHPV infection in 565 women with high-grade cervical lesions ranged from 77.2% to 100% and in 464 invasive cervical cancer samples from 89.8% to 100%. HPV16 was the most commonly detected hrHPV genotype in all categories. As the HPV genotype distribution in cervical diseases seems to be similar to that found in Western Europe the implementation of HPV testing in screening programs might be beneficial. Opportunistic screening programs, the lack of efficient call-recall systems, low coverage, and the absence of quality assured cytology with centralized screening registry are major reasons for low success rates of cervical cancer programs in many of the countries. Finally, HPV vaccination is currently not widely implemented in most of the twelve countries mainly due to pricing, availability, and limited awareness among public and health care providers. Country-specific research, organized nationwide screening programs, registries and well defined vaccination policies are needed. This article forms part of a Regional Report entitled "Comprehensive Control of HPV Infections and Related Diseases in the Central and Eastern Europe and Central Asia Region" Vaccine Volume 31, Supplement 7, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.

Effectiveness of oral contraceptive pills in a large U.S. cohort comparing progestogen and regimen.

OBJECTIVE: To estimate real-life effectiveness of oral contraceptive pills by progestogen, length of pill-free interval, and body mass index while focusing on the effect of progestogens with a long half-life and on 24-day oral contraceptive pills regimens. METHODS: Outcome data from 52,218 U.S. participants in the International Active Surveillance of Women Taking Oral Contraceptives­a large, prospective, controlled, noninterventional, long-term cohort study with active surveillance of the study participants­were used to analyze contraceptive failure in association with oral contraceptive pills use. Low loss to follow-up is ensured by a comprehensive follow-up procedure. Contraceptive failure rates are described by Pearl Index and life-table analysis. Inferential statistics for contraceptive failure are based on Cox regression models. RESULTS: Analyses are based on 1,634 unintended pregnancies during 73,269 woman-years of oral contraceptive pills exposure. Life-table estimates of contraceptive failure for a 24-day regimen of drospirenone and ethinyl estradiol and 21-day regimens of other progestogens were 2.1% and 3.5% after the first study year, and 4.7% and 6.7% after the third year. The adjusted hazard ratio was 0.7 (95% confidence interval 0.6­0.8). Direct comparisons of the 24-day and 21-day regimens of drospirenone and norethisterone, respectively, showed also lower contraceptive failure rates for 24-day regimens. Contraceptive failure rates adjusted for age, parity and educational level showed a slight increase with higher body mass index. CONCLUSION: The 24-day oral contraceptive regimens containing a progestogen with a long half-life show higher contraceptive effectiveness under routine medical conditions compared with conventional 21-day regimens. Obesity seems to be associated with a slight reduction of contraceptive effectiveness. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00335257. LEVEL OF EVIDENCE: II