Pathology

  • 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.