NCI conducted a randomized, controlled phase III trial of a vaccine to prevent human papillomavirus (HPV) 16 and 18 infections and their associated cervical lesions in an area of Costa Rica with high rates of cervical cancer. The vaccine, manufactured by Glaxo-Smith-Kline (GSK), is based on virus-like particle technology developed by NCI intramural investigators. Four years of follow-up have been completed among participants cross-over vaccination has occurred in both study groups. Extension of follow-up for up to ten years is now underway to assess the duration of protection and long-term effects of vaccination. The study has found no therapeutic effect for the vaccine in women previously infected with HPV. Evaluation of pooled data from the NCI-Costa Rica and independent GSK trials indicated no evidence overall for an effect of vaccination on pregnancies and their outcomes, but vaccination is not recommended for pregnant women or those who intend to get pregnant within three months of vaccination. Data from the trial demonstrated that three doses of the HPV vaccine may not be necessary, as similar vaccine efficacy against cervical HPV16/18 infection was observed among women who received two, and even a single dose, of the HPV vaccine after four years of follow-up. Investigators also reported that the HPV vaccine provides strong protection against anal HPV infections that could eventually lead to anal cancer.