It is well established that persistent infection with human papillomavirus (HPV) plays a central role in the pathogenesis of most types of squamous-cell cancer of the cervix, vagina, vulva, anus, and penis. Recent estimates of the cost of treating HPV and cervical cancer exceed $4.5 billion; this is more than the cost of any other single STD with the exception of HIV infection (1). Most invasive types of anogenital squamous-cell cancer of the genital tract and anus have been associated with HPV types 16, 18, 31, or 45, whereas most external genital warts are associated with HPV types 6 or 11 (6). Subclinical genital HPV infection occurs more frequently than visible genital warts and refers to manifestations of infection in the absence of visible genital warts, including situations where infection is diagnosed on the basis of characteristic cytologic features, squamous intraepithelial lesions (SIL), or on any genital skin by a viral nucleic acid (DNA or RNA) or capsid protein test for HPV. Recognition of the role of specific HPV types in cervical cancer and the advent of type-specific HPV tests have stimulated a focus on the use of HPV diagnostic tests in prevention of cervical cancer. Testing for HPV was recently proposed as a strategy to determine which women with low-grade cervical cytologic abnormalities require colposcopic evaluation. Several trials designed to clarify the role of HPV testing in the evaluation of low-grade cervical abnormalities indicate that HPV testing can be useful in the management of women with Papanicolaou tests that show atypical squamous cells of undetermined significance, but not in the management of low-grade SIL (43–44). At this time, data are insufficient to recommend routine HPV testing for other clinical purposes. No therapy has been identified that effectively eradicates persistent subclinical HPV infection. In the presence of coexistent SIL, management should be based on histopathologic findings and includes cryotherapy, laser ablation, cone biopsy, or loop electrosurgical excision procedure.