Human papillomavirus (HPV) is one of the most common viral sexually transmitted infections, and at least 35 different HPV types infect the anogenital 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 are associated with benign lesions-for example HPV G and 11-are characterized as low-risk types. Types without well-established clinical associations are grouped on the basis of genetic similarity to known high-risk or low-risk HPV types. Because cervical cancer develops over a number of years from precursor lesions that also contain the same HPV types as those detected in invasive disease, it is important to understand factors other than HPV that influence malignant conversion, The human papillomaviruses are small DNA viruses that infect and replicate in the nuclei of squamous epithelial cells. Viral transcription, translation, and replication are tightly linked to the differentiation state of the cell. The tight linkage of viral replication to terminal differentiation 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 understanding of the pathogenesis of HPV. Infection with oncogenic HPV types is not sufficient to cause cervical cancer Many more women are infected with high-risk HPV types than will ever develop preinvasive or invasive 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 development of cervical cancer. Polymorphisms in host tumor suppressor proteins may determine genetic susceptibility to the development of HPV-associated cervical cancel: Both viral and host factors need to be taken into account when considering the role of E-IPV in cervical cancer screening, 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 of the infection and has made HPV typing unreliable for prognosis. We must determine the role of other factors besides HPV type, such as viral integration and transcription, in addition to host factors to effectively use HPV in the clinical evaluation and management of women in cervical cancer screening and treatment. Given the role of HPV in the development of cervical cancer, vaccination against HPV may be a more effective method of disease control than Pap smear screening. Despite the 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 reflects the current lack of effective alternatives for the prevention or treatment of HPV-associated cervical disease. The pursuit of current and future HPV vaccine strategies will continue in parallel with our increasing understanding of the biology of infection and mechanisms of HPV oncogenesis.
