DESCRIPTION (Adapted from the Investigator's Abstract): Worldwide, invasive
cervical cancer (ICC) is the second most common cancer among women, and is
of particular importance in developing countries. It has become apparent
that women throughout the world are increasingly at risk for infection with
HIV-1 or HIV-2 (in West Africa); that most women acquiring HIV also are
infected with HPV; and that co-infection with these two viruses increases
risk for squamous cell neoplasia. Some have suggested that the increase in
cervical intraepithelial neoplasia (CIN) among women with HIV is the result
of HIV induced immunosuppression which permits prolonged and increased HPV
expression resulting in a greater likelihood of CIN. Others suggest direct
upregulation of HPV by HIV. However, there have not been any in vivo
studies examining the molecular basis for the increased risk of neoplasia
associated with HIV. We propose that the increased risk for CIN conferred
by HIV is related to alterations of molecular events which have been shown
to be important in the development of ICC. We hypothesize that ICC and
CIN2-3 present in HIV infected women will differ from that in HIV
seronegative women with respect to (i) the distribution of HPV-16 variants
present, (ii) the stage in the development of cervical neoplasia at which
telomerase is activated, and the levels of telomerase present, and (iii) the
proportion of CIN2-3 in which genomic mutations are detected. The proposed
study is a logical extension of our ongoing study in Senegal West Africa.
Samples from women enrolled in our ongoing cohort study will be used in the
proposed study. Additionally, we will recruit and biopsy women with
cervical intraepithelial neoplasia grades 1-3, atypia (ASCUS) and invasive
cancer. Learning more about interrelationships between HPV variants,
telomerase and genetic mutations in the pathogenesis of cervical cancer
should suggest new methods for identifying women (especially HIV infected
women) at highest risk for cancer, should aid in development of new
strategies to treat cervical neoplasia in women with HIV who have been shown
to be resistant to conventional ablative therapy, and could have
implications for prophylactic or therapeutic vaccine development.
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