Accumulating evidence strongly associates human papillomavirus (HPV)
infection with the development of cervical precancers and cancer. The
specific role of HPV in cervical neoplasia has not been established d few
studies to date have examined the natural history of HPV from latent
infection to neoplasia. Studies documenting the presence of HPV DNA in
disease free women suggest that co-factors are required by HPV for
neoplasia to occur. The purpose of this study is 1) to continue a
longitudinal natural history of human papillomavirus (HPV) from early
infection to high grade (HG) squamous intraepithelial lesion (SIL) in
young women who have had a history of a positive test for HPV DNA and to
continue the examination of cofactors (Chlamydia trachomatis, herpes
simplex virus, oral contraceptive use, cigarette use and biologic cervical
immaturity) associated with the development of low grade (LG) SIL and
HGSIL, 2) to examine within this cohort events, specifically viral
persistence or transition from low to high level persistence, that may
precede and predict the development of significant cervical disease and to
examine factors that influence these events. In addition, the study will
examine co-factors associated with the regression of LGSIL and associated
with HPV conversion from negative to positive in our cohort. Methods: 985
women (794 HPV positive and 191 HPV negative aged 13-22 years will have
been recruited into a case-control study. Women who participate are asked
to undergo a colposcopic examination and face-to-face interview. Women
with no evidence of HGSIL are enrolled in the longitudinal study. We
estimate that 799 women will be currently active in the prospective cohort
by June, 1994. Patients will be examined every 4 months (controls are seen
every 6 months) or until HGSIL develops. Colposcopic examinations,
cytology, test for C. trachomatis, herpes simplex virus, nicotine/cotinine
levels of cervical mucous and face-to-face interviews for information on
sexual behaviors, contraceptive use, and cigarette use will be performed
at scheduled intervals. Data analysis will emphasize the identification of
cofactors associated with LGSIL and HGSIL development with emphasis on the
role of persistence, transition from low to high level persistent
infection, and regression of LGSIL. The results from this study will be
related to the prevention and education of pre-cancer lesions in young
women as well as identifying a clinical model for the role of viruses in
abnormal cellular development.
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