Long-term follow-up of the risk for cervical intraepithelial neoplasia grade 2 or worse in HPV-negative women after conization.

Little research has been conducted on the long-term value of human papillomavirus (HPV) testing after conization. We investigated whether cytology adds to the value of a negative HPV test for long-term prediction of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In addition, we compared risk of CIN2+ following a negative HPV test in women after conization with that in women from the general population. During 2002-2005, 667 women treated for CIN2+ were tested for HPV and cytology 46 months after conization. Only HPV-negative women were included. Women participating in routine screening were age-matched with post-conization HPV-negative women, leaving 13,230 and 477 women, respectively, for analysis. By linkage to the Pathology Data Bank, we identified all cases of CIN2+ by December 2013. The 3-, 5-, 8- and 10-year risks for CIN2+ were 0.7, 0.9, 2.8 and 5.7% after a negative HPV test and 0.5, 0.8, 2.9 and 6.1% in HPV and cytology-negative women. HPV-negative women in the general population had similar 3-year and 5-year risks of 0.4 and 1.0%; thereafter, they had lower risks of 1.9% at 8 years and 2.7% at 10 years. Our results indicate that HPV testing may be used as a test of cure after conization. In the first 5 years after testing, the risk for CIN2+ of women who were HPV-negative at 34 months after conization was similar to that of HPV-negative women in the general population. After 67 years, however, women who have undergone conization may be at higher risk for CIN2+.

Role of human papillomavirus testing and cytology in follow-up after conization.

OBJECTIVE: Adequate follow-up of women who have undergone conization for high-grade cervical lesions is crucial in cervical cancer screening programs. We evaluated the performance of testing for high-risk human papillomavirus (HPV) types, cytology alone, and combined testing in predicting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) after conization. DESIGN: Prospective cohort study. SETTING: Denmark. POPULATION: 667 women attending for conization. METHODS: Cervical specimens were collected during 2002-2006 at first visit after conization for cytological examination and Hybrid Capture 2 detection of high-risk HPV. The women were passively followed until 2 years after first follow-up visit by linkage to the nationwide Pathology Data Bank. RESULTS: At first visit after conization (median time, 3.4 months), 20.4% were HPV-positive and 17.2% had atypical squamous intraepithelial lesions or more severe cytology (ASCUS+). The 2-year incidence of CIN2+ after conization was 3.6%. Sensitivity for detection of CIN2+ after conization was 81.0% [95% confidence interval (CI) 58.1-94.6] for positive cytology (ASCUS+ threshold) and 95.2% (95% CI 76.2-99.9) for HPV testing and for combined testing. Specificity of ASCUS+ cytology (85.2%; 95% CI 82.0-88.0) was higher than that of HPV testing (82.4%; 95% CI 79.0-85.4) and markedly higher than that of combined testing (73.2%; 95% CI 69.3-76.8). The margin status had no significant added value. CONCLUSIONS: Testing for high-risk HPV three to four months after conization is more sensitive than ASCUS+ cytology for identifying women at risk for relapse of CIN2+ within 2 years. Further studies are needed to evaluate whether HPV testing could be a stand-alone test in follow up after conization.

Persistence and reappearance of high-risk human papillomavirus after conization.

OBJECTIVE: Women with early cervical cancer or intraepithelial neoplasia grades 2 and 3 (CIN2+) are treated by conization; however, they still have a higher risk for subsequent CIN2+ than the general female population. Persistence of high-risk (HR) human papillomavirus (HPV) is a key factor in the development of CIN2+. We investigated persistence and reappearance of type-specific HR HPV infection after conization and evaluated possible co-factors. METHODS: During 2002-2006, cervical swabs from 604 women were collected before conization, at 4-6 months and at 8-12 months after conization. HPV was detected by HC2 and genotyped by LiPAv2. Information on co-factors was collected through a questionnaire. Associations were assessed by multivariate logistic regression analysis. RESULTS: HR HPV persistence rate was 9.5%. The α5/6 species were more likely to persist than α9 species (OR, 2.28; 95% CI, 1.11-4.70). For single infections, a doubling in viral load at enrolment increased the risk for persistence by 36% (95% CI, 1.13-1.63). In addition, margin status was associated with risk of persistence. Smoking, oral contraceptive use and severity of the cervical lesion did not significantly affect persistence. Among the HPV infections that had cleared, 2.2% reappeared. CONCLUSION: Our study indicates that viral load is important in predicting HPV persistence. The α5/6 species were most likely to persist. However, most of these HPV types have a lower carcinogenic potential than the α7/α9 species and may be by-standers. Further studies are needed to assess whether pre-conization viral load can also predict subsequent CIN2+.

The absolute risk of cervical abnormalities in high-risk human papillomavirus-positive, cytologically normal women over a 10-year period.

In spite of the success of cervical cytology as a cancer-screening 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 > or =CIN3 of 18% (14.6-21.5). Among older women where HPV may be added to general screening, the estimated absolute risk of > or =CIN3 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.

Risk of breast cancer after exposure to fertility drugs: results from a large Danish cohort study.

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 cancer risk after use of gonadotrophins, clomiphene, human chorionic gonadotrophin, or gonadotrophin-releasing hormone, whereas use of progesterone increased breast cancer risk (RR, 3.36; 95% confidence interval, 1.3-8.6). For all groups of fertility drugs, no relationships with number of cycles of use or years since first use of fertility drug were found. However, gonadotrophins may have a stronger effect on breast cancer risk among nulliparous women (RR, 1.69; 95% confidence interval, 1.03-2.77). Similar risk patterns were present for ductal, lobular, and tumors of other histologies, indicating identical etiologies. CONCLUSION: The results showed no strong association between breast cancer risk and use of fertility drugs. Follow-up is, however, needed to assess long-term breast cancer risk after use of progesterone and among nulliparous women exposed to gonadotrophins.

Determinants for non-use of contraception at first intercourse; a study of 10841 young Danish women from the general population.

Based on interview data from 10841 Danish women aged 20 to 29 years, determinants for non-use of contraception at first intercourse (NU) were studied. One-fourth of the women (n = 2704) reported NU, whereas condoms and oral contraceptives were used by, respectively, 59% and 15%. NU decreased with the birth year of the first male partner (OR = 3.6; 95% CI: 2.8-4.8 for or=17 years) at the expense of both oral contraception and condom use. Finally, NU was found to predict high-risk sexual behavior in terms of subsequent multiple sex partners, non-use of condoms, and induced abortion.

[Human papillomavirus and the risk of anogenital cancer]. / Human papillomavirus og risiko for anogenital kraeft.

Strong evidence suggests that virtually all cases of cervical cancer are caused by infection with oncognenic types of human papillomavirus (HPV). HPV is also found frequently in neighbouring anogenital epithelia and their neoplastic lesions. This review describes the general aspects of the natural history of anogenital HPV infections and summarises the evidence for an association between HPV and cancers of the uterine cervix, vulva, anus and penis.

[Who are the users of emergency contraception?]. / Hvem anvender nødpraevention?

INTRODUCTION: A user profile is necessary in order to direct future campaigns for emergency contraception (EC). MATERIAL AND METHODS: Over a three-month period, 423 women with prescriptions for EC were consecutively entered in the study, which was carried out in four inner-city pharmacies in Copenhagen, Denmark. RESULTS: The median age was 24 years (range 13-50 years). Most women (73%) were first-time users of EC. The reason for the current need for EC was most often condom failure (54%) or non-use of any contraceptive method (41%). Only six women (1.4%) reported non-use of contraception because of their knowledge of EC and only four women (0.9%) reported EC as the usual method of contraception. Knowledge about EC more often came from family or friends (51%) and advertising (47%), than from general practitioners (26%) or through sex education in schools (3%). Altogether 282 women (69%) received EC from a doctor in the medical emergency service or a casualty ward. DISCUSSION: Overall, EC is used as recommended. Its availability does not seem to reduce the use of safer contraceptive methods. The mandatory sex education in school should include information on EC.

The role of smoking and alcohol intake in the development of high-grade squamous intraepithelial lesions among high-risk HPV-positive women.

BACKGROUND: Infection with human papillomavirus is considered a necessary factor in developing high-grade squamous intraepithelial lesions of the cervix. However, most human papillomavirus positive women do not develop high-grade squamous intraepithelial lesions and other factors may be important for this transition. The objective of the present study was to examine if smoking and alcohol intake are associated with the risk of developing high-grade squamous intraepithelial lesions in women positive for high-risk human papillomavirus types. METHODS: We used baseline information on exposures on 548 high-risk human papillomavirus positive women with normal cytology, comparing 94 women who developed high-grade squamous intraepithelial lesions with 454 women who remained cytologically normal. Logistic regression was applied for statistical analysis. RESULTS: Compared with never smokers, the odds ratio for high-grade squamous intraepithelial lesions among current smokers was 1.99 (95% CI: 1.21-3.28). Among current smokers, number of cigarettes, years of smoking, and early age at smoking initiation were associated with increased risk. However, when modeled simultaneously, it seemed that smoking duration and age at smoking initiation were more associated with risk of high-grade squamous intraepithelial lesions than amount of smoking. Alcohol intake was not associated with risk of high-grade squamous intraepithelial lesions among these women. CONCLUSION: Smoking is associated with an increased risk of developing high-grade squamous intraepithelial lesions in women who are infected with oncogenic human papillomavirus.

Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study.

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 enrollment and at the second examination about two years later. RESULTS: Compared with women who were negative for human papillomavirus at enrollment, 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.