Our virus laboratory investigates human diseases associated with papillomaviruses and polyomaviruses, in close collaboration with Dr. Maura Gillison (Oncology) and Dr Patti Gravitt (Epidemiology)

Human papillomaviruses (HPVs) are small DNA viruses that naturally fall into cutaneous and mucosal types. About 40 mucosal HPVs inhabit the genital tract. We participated in research that established that infection with any one of a subset of these HPVs is the primary and necessary event that eventually leads to invasive cervical cancer. There are about 500,000 cases of cervical cancer, annually, worldwide.

Our current research in HPVs is centered around the following topics. The genital tract HPVs that cause cervical cancer also seem to be etiologically linked to about one half of cancers of the oropharynx. We are examining the virologic and clinical characteristics of these cancers and also how alcohol and tobacco use may interact with HPV infections in the development of these cancers. We are planning to test if patients with these cancers will benefit from HPV-based therapeutic vaccines that are being developed for the treatment of cervical cancer. In a second area, we have projects in collaboration with investigators in India which are aimed at comparing HPV-based and other screening strategies (including Pap smears) for detection of pre-invasive cervical disease and in identifying cellular and viral biomarkers which might be predictive of progression to high grade pre-invasive or to invasive cervical cancer. We are also studying an HPV-caused disease in children, juvenile-onset recurrent respiratory papillomatosis (JORRP), in which benign papillomas, most often located on the vocal cords, may result in life-threatening respiratory obstruction. The HPV types that cause JORRP are transmitted from an infected mother to the child at the time of birth. We are investigating if cesarean delivery would prevent JORRP and if the risk of transmission varies with the infecting virus type.

We are investigating the pathogenic potential of human polyomaviruses BKV and JCV, and the rhesus polyomavirus SV40.Some recent reports imply that SV40, which was an inadvertent contaminant of polio vaccines administered in the late 1950's is now established as a human infection, and that it contributes to the development of a number of human cancers. We are investigating this possibility by studying cancer patients and controls for virological and serological markers of SV40 infection, and by examination of cancer tissues for SV40 sequences. Our results to date do not indicate that SV40 is a human carcinogen.

Molecular Microbiology and Immunology, human papillomaviruses, cervical cancer, epidemiology, polyomaviruses

Castellsague X, Bosch FX, Munoz N, Meijer CJLM, Shah KV, de Sanjose S, Eluf-Neto J, Ngelangel C, Chichareon S, Smith J, Herrero R, Franceschi S for the IARC Multicentric Cervical Cancer Study Group: Male circumcision, penile human papillomavirus infection and cervical cancer. N Engl J Med 346:1105-12, 2002.

Bosch FX, Lorincz A, Munoz N, Meijer CJ, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 55:244-265, 2002.

Engels AE, Sarkar C, Daniel RW, Gravitt PE, Verma K, Quezado M, Shah KV: Absence

of Simian Virus 40 in human brain tumors from Northern India. Int J Cancer 101: 348-

352, 2002.

The International SV40 Working Group (KV Shah, member): A multicenter evaluation of assays for detection of SV40 DNA and results in masked mesothelioma specimens. Cancer Epidemiol Biomarkers Prev 10: 523-532, 2001.

Shah KV: Does SV40 infection contribute to the development of human cancers? Rev

Med Virol 10: 31-43, 2000.

Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML,

Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D: Evidence for a causal

association between human papillomavirus and a subset of head and neck cancers.

JNCI 92: 709-720, 2000.

Walboomers JMM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJF, Peto J, Meijer CJLM and Muñoz N: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12-19, 1999.