Human papillomaviruses (primarily HPV 16 and 18) play a central role in the development of in situ and invasive cervical cancer. Based on this observation and the well-recognized shortcomings of Pap smears, several groups have examined the use of HPV DNA testing as an adjunct to cytologic screening and found it to be cost effective. Consequently, a number of laboratories throughout the U.S. have begun offering HPV DNA tests, and in doing so, have left many clinicians and their clients with questions that currently do not have answers. Although the potential consequences of genital HPV infection are well documented, we know relatively little about the long-term implication; of a single or repeatedly positive type-specific HPV DNA test result. Furthermore, it is likely that HPV vaccines will introduced to prevent cervical cancer and, perhaps, genital warts in the future. However, knowledge of the infectivity and natural history of specific HPV types is essential for evaluating the impact and feasibility of vaccines. Much of this required knowledge is currently lacking. Since 1991, we have been studying the short term natural history of HPV in a cohort study of 600 freshman women and are now in a position to build on and extend these studies to gain an understanding of the longer-term natural history of genital HPV infection and of male to female transmission rates. Our specific aims are to l) define the natural history of genital HPV infection over ten years with respect to persistent detection of HPV DNA, SIL, genital warts, and HPV type-specific antibodies, 2) determine the prevalence, seroprevalence, and behavioral predictors of genital HPV infection among a random sample of male undergraduate students, and 3) estimate per partner and per act transmission rates of specific HPV types and define characteristics of partnerships (e.g., courtship behavior, condom use, and frequency of intercourse) and of partners (e.g., age, race, occupation, number of partners, circumcision status, and report of concurrent relationships) that affect transmission. The proposed study is likely to provide important information relevant to the development of effective HPV prevention strategies, including the synthesis of accurate and informative public health messages concerning the transmissibility of HPV and the meaning of a single or repeatedly positive HPV DNA test. Additionally, these data will provide investigators working on HPV vaccine development with information that is needed to guide the selection of appropriate target populations, outcome measures, and immunization strategies.