Incidence and duration of cervical human papillomavirus 6, 11, 16, and 18 infections in young women: An evaluation from multiple analytic perspectives
ABSTRACT To estimate the incidence and duration of cervical human papillomavirus (HPV)-6, HPV-11, HPV-16, and HPV-18 infections in a population of young American women.
The study population consisted of U.S. women who at baseline were 16 to 23 years of age, reported zero to five lifetime sexual partners, never having been pregnant, and never having had a prior abnormal Papanicolaou test and were enrolled in the placebo arm of a randomized multicenter clinical trial of a HPV-16 L1 virus-like particle vaccine. Women underwent type-specific endocervical/ectocervical swab HPV DNA testing at approximately 6-month intervals for up to 48 months of follow-up. To contribute person-time in the analyses of type-specific HPV incidence, a woman must have had at least three satisfactory swab specimens available and been negative for the relevant HPV type (HPV-6, HPV-11, HPV-16, or HPV-18) on her first two trial swabs. The duration of incident HPV infections was estimated using Kaplan-Meier survival analysis methods.
Person-years of exposure ranged by type-specific analysis from 2,645 to 3,188, with an incidence rate per 100 person-years of 3.6 for HPV-6, 0.4 for HPV-11, 5.4 for HPV-16, and 2.1 for HPV-18. With censoring at the time of treatment for cervical intraepithelial neoplasia, where done, the mean duration of incident infections was 9.3, 8.4, 18.2, and 16.4 months, respectively, for HPV-6 (n = 103), HPV-11 (n = 13), HPV-16 (n = 142), and HPV-18 (n = 62). When the duration of HPV infections was truncated at the time of cervical intraepithelial neoplasia detection (any grade), where applicable, mean duration figures were 8.4, 8.1, 14.0, and 15.1 months for HPV-6, HPV-11, HPV-16, and HPV-18 infections, respectively.
Previous studies of the mean duration of cervical HPV infection have been based on prevalent infections and/or featured relatively short duration of follow-up. This study tested women for HPV infection over a period of up to 48 months and observed a mean duration of incident HPV-16/HPV-18 infections approximately twice that of HPV-6/HPV-11.
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ABSTRACT: Cervical cancer screening guidelines do not comprehensively define what constitutes high risk. This study developed and validated simple risk-scoring schemes to improve Papanicolaou smear screening for women at high risk. Four cumulative risk score (CRS) schemes were derived respectively for the development of cervical intraepithelial neoplasia grade 1 (CIN1) and grade 2 or worse (CIN2+) using community-based case-control data (n=1523). By calculating the area under the receiver operating characteristic (AU-ROC) curve, these schemes were validated in a Papanicolaou smear follow-up cohort (n=967) and a hospital-based cytology screening population (n=217). A high DNA load of high-risk human papillomavirus (HR-HPV) was the main predictor for CIN1 and CIN2+, although age, married status combined with the number of sexual partners, active and passive smoking and age at sexual debut also affected associated lesions. In the training set, only the HPV-testing-contained CIN2+ CRS scheme presented an excellent discrimination for identifying CIN2+ (AU-ROC=0.866). By using a CRS cutoff value of 4 to identify CIN2+, the sensitivity and specificity of predicting CIN2+ for the 3- and 5-year follow-ups were 100% and 90.8%, and 83.3% and 90.4%, respectively, in the validation cohort. In the hospital-based validation population, the CRS scheme showed comparable discrimination for CIN2+ detection (sensitivity 88.2% and specificity 84.6%). Women with CRS ≥4 had a 5.4% and 9.1% of 3- and 5-year cumulative incidence, respectively, and a 40.5-fold hazard ratio of developing CIN2+. In conclusion, combined with HR-HPV testing and verified risk factors, a simple CRS scheme could effectively improve the implementation of CIN2+ screening. © 2014 Wiley Periodicals, Inc.International Journal of Cancer 01/2015; 136(2). DOI:10.1002/ijc.28982 · 5.01 Impact Factor
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ABSTRACT: Human papillomavirus (HPV) vaccines have the potential to reduce cervical cancer incidence and mortality, particularly in the parts of the developing world that bear the greatest burden of disease. This research sought to predict the impact and cost-effectiveness of an HPV vaccination program in an example low-resource country with a high burden of cervical cancer: Mali, West Africa. Novel compartmental mathematical models projected the impact of adolescent HPV vaccination in urban and rural areas of Mali. The models accounted for two high-risk vaccine-types: HPV 16 and 18. We then attached comprehensive real cost and cost-effectiveness estimates. Our models predict that HPV vaccination in Mali will reduce cervical cancer burden by a factor roughly equal to vaccine coverage. A point vaccination program was simulated in a cohort of 333,146 urban and 588,982 rural Malian women, age 10-14. Vaccination of 50% of girls reduced the peak prevalence of HPV 16/18 to 5.0% in the urban setting and 9.6% in the rural setting, down from 11.7% and 22.0%, respectively, with no vaccination. The 50% vaccination scenario averted 1145 cervical cancer deaths in the urban group and 3887 in the rural group. The cost per discounted life-year saved in this scenario was 1030 US dollars (urban) and 725 dollars (rural). The cost per life-year saved was higher at 90% coverage, but was still in the range of a "cost-effective" public health intervention. This research yielded the most comprehensive real cost estimates of HPV vaccination yet published for sub-Saharan Africa. Our models indicate that HPV vaccination in Mali will be cost-effective when introduced. To maximize the benefit using limited resources, vaccination programs may begin with a target coverage of about 50%. We anticipate that costs of reaching late adopters after the First Vaccinated Wave of vaccination will be higher, but worthwhile.Vaccine 04/2014; 32(26). DOI:10.1016/j.vaccine.2014.03.067 · 3.49 Impact Factor