||3R21CA124324-02S1 Interpret this number
||University Of California Los Angeles
||Methylation and Related Anogenital HPV Cancers
Anal cancer is an emerging health crisis for homosexual men, especially within the context of human
mmunodeficiency virus (HIV) infection. Like invasive cervical cancer, intra-anal cancers are largely
attributable to chronic, high-risk human papillomavirus (HPV) infections. These infections and their
associated low- and high-grade anal intraepithelial neoplasias (AIM) are common for men with a history of
receptive anal intercourse. Though the prevalence of anal dysplasia is high, malignancy is a relatively rare
occurrence. Domestically, there is no consensus for standards of care, and the outcome of treatment
algorithms is largely unsatisfactory. There is an urgent need to identify key events in the underlying natural
history of disease, which will enable clinicians to determine which individuals need immediate treatment or
can remain under careful surveillance. More sensitive biomarkersthat can discriminate between men likely
to progress from those that do not will allow better clinical algorithms to be tested. In the long term, these
strategies will reduce morbidity and mortality and diminish the population's burden of disease.
Methylation is an adaptive cellular process that hinders transcription of foreign DMA by making viral
genomes less accessible to host-cell transcription factors and enzymes. Our recent studies suggest
methylation of HPV genomes may be an epigenetic determinant, responsible for promoting latent infection
and clinical disease progression. This investigation focuses on two aims using epidemiological methods and
molecular biology techniques. First, we will determine whether previously observed relationships between
methylation of HPV16 genomes and disease state are observable in 91 HIV/HPV16 coinfected men that
have been evaluated for AIM. Second, using longitudinally-collected clinical samples and controlling for the
effect of time-dependent covariates, we will determine whether particular baseline patterns of methylation in
HPV16 genomes predict methylation patterns overtime in three high-risk HPVs.
PUBLIC HEALTH STATEMENT: The findings from this study will improve the public's health by
improving anal cancer screening accuracy through the identification of reliable biomarkers, to ultimately
prevent premature death.
None. See parent grant details.