HUMAN-PAPILLOMAVIRUS AND CERVICAL-CANCER

Human papillomavirus (HPV) is one of the most common viral sexually tr ansmitted infections, and at least 35 different HPV types infect the a nogenital mucosa. Only a few of these anogenital HPV types-for example , HPV 16 and 18-have been consistently associated with cervical cancer and thus have been characterized as high-risk HPV types. Those that a re associated with benign lesions-for example HPV G and 11-are charact erized as low-risk types. Types without well-established clinical asso ciations are grouped on the basis of genetic similarity to known high- risk or low-risk HPV types. Because cervical cancer develops over a nu mber of years from precursor lesions that also contain the same HPV ty pes as those detected in invasive disease, it is important to understa nd factors other than HPV that influence malignant conversion, The hum an papillomaviruses are small DNA viruses that infect and replicate in the nuclei of squamous epithelial cells. Viral transcription, transla tion, and replication are tightly linked to the differentiation state of the cell. The tight linkage of viral replication to terminal differ entiation has made tissue culture propagation of the virus difficult. Nevertheless, molecular biology techniques have allowed the study and functional analysis of most of the 8 viral proteins to further our und erstanding of the pathogenesis of HPV. Infection with oncogenic HPV ty pes is not sufficient to cause cervical cancer Many more women are inf ected with high-risk HPV types than will ever develop preinvasive or i nvasive disease. We now know that numerous host factors influence the development and persistence of papillomavirus-induced lesions. Immune recognition of the virus governs the host's resistance to the developm ent of cervical cancer. Polymorphisms in host tumor suppressor protein s may determine genetic susceptibility to the development of HPV-assoc iated cervical cancel: Both viral and host factors need to be taken in to account when considering the role of E-IPV in cervical cancer scree ning, treatment, and prognosis. The sensitivity and specificity of FDA -approved HPV tests does not warrant basing cervical disease screening and treatment solely on HPV testing. In addition, characterization of HPV type does not adequately reflect the potential oncogenic impact o f the infection and has made HPV typing unreliable for prognosis. We m ust determine the role of other factors besides HPV type, such as vira l integration and transcription, in addition to host factors to effect ively use HPV in the clinical evaluation and management of women in ce rvical cancer screening and treatment. Given the role of HPV in the de velopment of cervical cancer, vaccination against HPV may be a more ef fective method of disease control than Pap smear screening. Despite th e gaps in our knowledge of the natural history of HPV and the role of the immune response to HPV, both prophylactic and therapeutic vaccine trials are underway. The expediency of the vaccine trials likely refle cts the current lack of effective alternatives for the prevention or t reatment of HPV-associated cervical disease. The pursuit of current an d future HPV vaccine strategies will continue in parallel with our inc reasing understanding of the biology of infection and mechanisms of HP V oncogenesis.