Dr. Keerti Shah
Professor of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health
Joint Appoinment in Oncology
M.B.B.S. B.J. College, Poona, India
M.P.H. Johns Hopkins Bloomberg School of Public Health
Ph.D. Johns Hopkins Bloomberg School of Public Health (Virology)
Our virus laboratory investigates human diseases associated with papillomaviruses and polyomaviruses.
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. Annually, there are about 500,000 cases of cervical cancer worldwide.
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 that 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 that might be predictive of progression to high- grade pre-invasive or 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 caesarean 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 1950s, is now established as a human infection and 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.
Bhatla, N., Dar, L., Rajkumar Patro, A., Kumar, P., Pati, S.K., Kriplani, A., Gulati, A., Broor, S., Iyer, V.K., Mathur, S., Shah, K.V., and Gravitt, P.E. (2008). Human papillomavirus-type distribution in women with and without cervical neoplasia in north India. Int J Gynecol Pathol 27, 426-430.
Eberhart, C. G., Chaudhry, A., Daniel, R. W., Khaki, L., Shah, K. V. & Gravitt, P. E. (2005). Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus. BMC Cancer 5, 19.
Flores, Y.N., Bishai, D.M., Shah, K.V., Lazcano-Ponce, E., Lorincz, A., Hernandez, M., Ferris, D., and Salmeron, J. (2008). Risk factors for cervical cancer among HPV positive women in Mexico. Salud Publica Mex 50, 49-58.
Paramsothy, P., Jamieson, D.J., Heilig, C.M., Schuman, P.C., Klein, R.S., Shah, K.V., Rompalo, A.M., Cu-Uvin, S., and Duerr, A. (2009). The effect of highly active antiretroviral therapy on human papillomavirus clearance and cervical cytology. Obstet Gynecol 113, 26-31.
Rollison, D. E., Utaipat, U., Ryschkewitsch, C., Hou, J., Goldthwaite, P., Daniel, R., Helzlsouer, K. J., Burger, P. C., Shah, K. V. & Major, E. O. (2005). Investigation of human brain tumors for the presence of polyomavirus genome sequences by two independent laboratories. International Journal of Cancer.Journal International Du Cancer 113, 769-774.
Safaeian, M., Kiddugavu, M., Gravitt, P.E., Gange, S.J., Ssekasanvu, J., Murokora, D., Sklar, M., Serwadda, D., Wawer, M.J., Shah, K.V., and Gray, R. (2008). Determinants of incidence and clearance of high-risk human papillomavirus infections in rural Rakai, Uganda. Cancer Epidemiol Biomarkers Prev 17, 1300-1307.
Safaeian, M., Kiddugavu, M., Gravitt, P.E., Gange, S.J., Ssekasanvu, J., Murokora, D., Sklar, M., Serwadda, D., Wawer, M.J., Shah, K.V., and Gray, R. (2008). Prevalence and risk factors for carcinogenic human papillomavirus infections in rural Rakai, Uganda. Sex Transm Infect 84, 306-311.
Shah, K. V., and W. H. Westra. 2007. Genital HPVs in the aerodigestive tract: Etiologic association with a subset of oropharyngeal/tonsillar cancers and with recurrent respiratory papillomatosis. Dis Markers 23:235-45.
Shah, K.V. (2008). Asia Pacific: Cervical cancer screening and human papillomavirus vaccination policy and delivery. Vaccine 26 Suppl 12, iii-iv.
Bosch, F. X., Lorincz, A., Munoz, N., Meijer, C. J., & Shah, K. V. 2002. The causal relation between human papillomavirus and cervical cancer. J. Clin. Pathol. 55:244-265.
Castellsague, X., Bosch, F. X., Munoz, N., Meijer, C. J. L. M., Shah, K. V., de Sanjose, S., et al. 2002. Male circumcision, penile human papillomavirus infection and cervical cancer. [For the IARC Multicentric Cervical Cancer Study Group]. N. Engl. J. Med. 346:1105-1112.
Shah, K. V. 2004. Simian virus 40 and human disease. [Editorial]. J. Infect. Dis. 190:2061-2064.