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Contains fulltext : 216687.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 197712.pdf (publisher's version ) (Open Access)

Radboud Universiteit Nijmegen, 22 maart 2012, Promotor : Massuger, L.F.A.G. Co-promotores : Bekkers, R.L.M., Melchers, W.J.G., Contains fulltext : 92743.pdf (publisher's version ) (Open Access)

Contains fulltext : 108165.pdf (publisher's version ) (Closed access), Objective: To study the prevalence, incidence, and clearance of human papillomavirus (HPV) in pregnant and nonpregnant women. Methods: In this prospective matched cohort study, 51 women, became pregnant during follow-up of an HPV epidemiology study (n=2065), and 51 matched nonpregnant women were included. All women provided 3-monthly cervicovaginal self-samples and completed a questionnaire. The PCR SPF(10) LiPA(25) was used for HPV testing. Matching was performed using a propensity score. Results: The cumulative prevalence of high-risk HPV (hrHPV) was 19.6% (n=10) of the pregnant and 17.6% (n=9) of the matched control women. The time point prevalence of any type HPV and hrHPV was not significantly different for pregnant and matched control women. After baseline, there were 10 newly detected hrHPV types in 6 (11.8%) of the pregnant women, and there were 11 newly detected hrHPV types in 8 (15.7%) of the matched control women. There was no difference in HPV clearance between pregnant and matched control women. Conclusions: This study shows that in a low-parity population of young, unscreened women, pregnancy does not seem to influence HPV prevalence, incidence, and clearance.

Contains fulltext : 95972.pdf (publisher's version ) (Open Access), OBJECTIVE: To evaluate hr-HPV persistence and associated risk factors in a prospective cohort of young unscreened women. Additionally, the relation between hr-HPV status and cytology/histology results is examined. METHODS AND PRINCIPAL FINDINGS: Two year follow-up of 235 out of 2065 young women (18-29 years), participating in a large, one year epidemiological study, with questionnaires, self-collected cervico-vaginal samples (Vibabrush), and SPF(10)LiPA for HPV detection. Only women hr-HPV positive at sample month 12 were invited for a second year of follow-up. After study follow-up, available cytology/histology data were requested from PALGA (the national network and registry of histo- and cytopathology in The Netherlands). These data were compared with available cytology/histology data of the month 12 hr-HPV negative women from the same cohort. 44.1% of the hr-HPV types detected at study month 12, persisted during follow-up. HPV types 45, 31, 16 and 18 were most likely to persist with percentages of 60.0%, 56.8%, 54.4%,and 50.0%, respectively. Compared to newly detected infections at month 12, infections present since 6 months or baseline had an increased risk to persist (OR 3.09 [95% CI: 1.74-5.51] and OR 4.99 [95% CI: 2.67-9.32], respectively). Other co-factors influencing persistence were, multiple HPV infections, smoking and multiple lifetime sexual partners. The percentage of women with a HSIL/CIN2+ (12.1%) in the persistent HPV group, was not significantly different (p = 0.107) from the 5.3% of the women who cleared the hr-HPV infection, but was significantly (p 0.000) higher than to the 1.6% of women in the hr-HPV negative control group. CONCLUSION: We showed that HPV genotype, multiple infections, smoking, and multiple lifetime sexual partners are co-factors that increase the risk of hr-HPV persistency. Most importantly, we showed that hr-HPV infections are more likely to persist the longer they have been present and that women with a persistent hr-HPV inf

Contains fulltext : 98451.pdf (publisher's version ) (Closed access), High-risk human papillomavirus (hr-HPV) detection will become an important tool in the screening for cervical cancer. Self-sampling is an inexpensive and well-accepted method for HPV detection that will increase participation of nonresponders in current screening programs. Even more, because self-collected samples are as good as physician-collected samples for HPV detection, self-sampling might be a suitable method for future primary cervical cancer screening.

Item does not contain fulltext, BACKGROUND: To evaluate co-administration of GlaxoSmithKline Biologicals' human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB). METHODS: This was a randomized, controlled, open, multicenter study. Healthy girls, aged 9-15 years, were randomized to receive HPV (n=247), HepB (n=247) or HPV co-administered with HepB (HPV+HepB; n=247) at Months 0, 1 and 6. Antibodies against hepatitis B surface antigen (HBs), HPV-16 and HPV-18 were measured, and reactogenicity and safety monitored. Co-primary objectives were to demonstrate non-inferiority of hepatitis B and HPV-16/18 immune responses at Month 7 for co-administered vaccines, compared with vaccines administered alone, in the according-to-protocol cohort. RESULTS: The pre-defined criteria for non-inferiority were met for all co-primary immunogenicity endpoints at Month 7. Anti-HBs seroprotection rates >/=10mIU/mL were achieved by 97.9% and 100% of girls, respectively, following co-administration or HepB alone. Anti-HBs geometric mean titers (GMTs) (95% confidence interval) were 1280.9 (973.3-1685.7) and 3107.7 (2473.1-3905.1) milli-international units/mL, respectively. Anti-HPV-16 and -18 seroconversion rates were achieved by >/=99% of girls following co-administration or HPV alone. Anti-HPV-16 GMTs were 19819.8 (16856.9-23303.6) and 21712.6 (19460.2-24225.6) ELISA units (ELU)/mL, respectively. Anti-HPV-18 GMTs were 8835.1 (7636.3-10222.1) and 8838.6 (7948.5-9828.4) ELU/mL, respectively. Co-administration was generally well tolerated. CONCLUSIONS: The study results support the co-administration of HPV-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine in adolescent girls aged 9-15 years. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov registration number NCT00652938.

Item does not contain fulltext, PURPOSE: To investigate the effect of implementation of the HPV vaccine on HPV knowledge and HPV vaccine acceptance. METHODS: From June until December 2009 in Nijmegen, the Netherlands, 698 male and female students aged 18-25 years were recruited and interviewed about HPV, cervical carcinoma and HPV vaccine acceptance. RESULTS: Of all participants 46.6% had never heard of HPV. Women and students from the medical faculty were significantly more aware of HPV. Acceptance of a "catch-up" HPV vaccination in women was 51% and in men 27%. Acceptance of the HPV vaccination for 12-year old girls was 79%. CONCLUSION: After implementation of the HPV vaccine in the national vaccination program, > 50% of the students lack knowledge on HPV. Acceptance of a "catch-up" HPV vaccination was low. However, the acceptance of HPV vaccination for 12-year-old girls was high. Vaccine implementation strategies, focusing on 12-16 year old girls, might have caused this difference. Young adults need to be informed that the HPV vaccine may still be efficient when they are sexually active, but HPV 16 and 18 negative.

1 juli 2010, Contains fulltext : 88745.pdf (publisher's version ) (Closed access), OBJECTIVE: To estimate the effect of the menstrual cycle and oral contraceptive pill (OCP) use on the prevalence, incidence, and persistence of human papillomavirus (HPV). METHODS: A longitudinal study was conducted among 2,065 women aged 18-29 years. The women returned a self-collected cervicovaginal sample and filled out a questionnaire. A total of 1,812 women participated at all three time points, month 0, month 6, and month 12. RESULTS: Low- and high-risk HPV prevalence at study entry was 8.9% and 11.8%, respectively. The annual incidence of low-risk HPV infections was 12.5% and the persistence was 2.0%. For high-risk HPV, the incidence and persistence was 12.1% and 4.5%, respectively. These results did not differ between OCP users and nonusers. A significant relationship between high-risk HPV detection and the timing of sampling was found when OCP users and nonusers were analyzed separately. In the second half of the menstrual cycle, high-risk HPV detection decreased in nonusers (P=.007) and increased in OCP users (P=.021). When women used OCPs continuously, high-risk HPV detection returned to the level of the first half of the menstrual cycle. CONCLUSION: High-risk HPV detection was significantly influenced by sample timing in the menstrual cycle when analyzed separately for OCP users and women with a natural menstrual cycle. This may have implications in the future, when high-risk HPV detection may become a primary screening tool in cervical cancer prevention. LEVEL OF EVIDENCE: II.

Contains fulltext : 69205.pdf (publisher's version ) (Closed access), A recently published meta-analysis and a large cohort study showed independently that use of oral contraceptives (OC) leads to an increased relative risk (RR) of cervical cancer. This RR increased with the duration of OC use and was 1.90 after 5 years or more (95% CI: 1.69-2.13). The increased RR decreased after cessation of OC use and was normal again Io years later. Longstanding OC use enhances human papillomavirus (HPV) transcription and decreases HPV clearance, resulting in more frequent persistence of HPV, an increase of cervical intraepithelial neoplasia, and an increased RR of cervical cancer. The increase in cervical cancer by OC is, however, associated with a fully compensatory decrease in the incidence of other malignancies, in particular ovarian cancer and endometrial cancer. Based on these findings, there are no reasons to discourage the use of OC by women in the Netherlands.