This chapter focuses on the two anatomical sites where human papillomavirus (HPV) infection wreaks the majority of its havoc in women; namely, the cervix and the anus. According to the Centers for Disease Control and Prevention (CDC), HPV is the most common sexually transmitted infection (STI) in the United States. There are three recommended screening modalities: cytology alone, HPV DNA testing alone, and finally cotesting using both cytology and HPV DNA testing. The HPV type affects the likelihood of persistence and the risk of progression to precancer. Populations of women who are at risk of anal HPV-associated pathology have been identified and health care providers should have a heightened awareness, to include the anus and perianus for clinical evaluation. In 2010, Food and Drug Administration (FDA) added prevention of anal intraepithelial neoplasia (AIN) and anal cancer in both men and women as an approved indication for the quadrivalent HPV vaccine.