Lubomir P. Turek, MD
Research Laboratory
Contact Information
Phone: 319-158-7504, Ext 7504
VA Health Care System
Molecular Biology and Epidemiology of Human Papillomavirus Infection in Head and Neck Cancer
Oncogenic or "high-risk" (HR) human papillomavirus (HPV) types cause
cervical cancer and other anogenital malignancies. Our group was one of
the first to provide evidence that HR HPV type 16 also is causally
associated with some head and neck cancers (HNC), especially those
located in the tonsillar area and oropharynx. We investigate the
molecular biology and molecular epidemiology of HPV in HNC
carcinogenesis.
HNC represents a unique opportunity to study a cancer that presents
clinically as a single disease yet has two distinct etiologies:
HPV-associated and HPV-independent, associated with tobacco and alcohol
use. Although the HPV-associated HNC often occurs in younger patients
and presents as more advanced disease, we and others have shown that
patients with HPV-associated HNC have better prognosis and survival. In
our epidemiologic studies, we are developing diagnostic and prognostic
molecular markers of HPV-associated and HPV-independent HNC.
In our molecular and cell biology projects, we are interested in the
progression of the HR HPV-infected cell to cancer. In the infected cell
as well as in premalignant clinical lesions, HPV genomes persist as
extrachromosomal, supercoiled circular plasmids in the cell nucleus. In
many cervical carcinomas and HNCs, however, HPV DNA is integrated in the
cellular genome in a way that preserves the viral E6-E7 oncogenes yet
disrupts those viral genes that are required for HPV genome replication
and gene regulation in plasmid persistence, the E1 and E2 genes. We have
developed a colony immortalization assay that allows us to quantitate
the ability of HR HPV genomes and mutants to extend the life span of
primary human keratinocytes in cell culture. From these experiments, we
have isolated and characterized sets of isogenic, immortalized
keratinocyte cell clones that maintain HR HPV persistence as
unintegrated, plasmid genomes in long-term culture. We are using these
cells to study HPV integration and to test treatments that would
eliminate HPV plasmid genomes from persistently infected cells, yet
would not induce unintended integration that may promote cancer
development.
Both approaches use state-of-the-art molecular, genetic and biochemical
methods and involve extensive collaborations with colleagues at the
local, national and international level.