Abstract Besides cervical cancer, the human papillomavirus (HPV) is found in other cancers and may be preventable with HPV vaccination. However, these other cancers are often not accounted for in cost-effectiveness analyses of HPV vaccination. This study estimates the potential maximum effect on the cost-effectiveness ratio (CER) of HPV vaccination in preventing non-cervical HPV-positive cancers. For the Dutch situation, a mathematical equation was used to estimate the maximum impact if all cancer cases of the penis, vulva/vagina, anus, oral cavity and oro-pharynx with HPV16/18 are prevented, in terms of number of life years gained, savings and improvement in the CER of the vaccination. For other countries and for future developments, we show how the impact on the CER varies depending on the incidence of cervical/non-cervical HPV 16/18-positive cancers, vaccine costs and clinical costs. If in the Netherlands all HPV 16/18-positive cancers are prevented by vaccination in women only, compared to if only HPV 16/18-positive cervical cancer is prevented, the life years gained increase with 14%, the savings increase with 18%, and the CER decreases with 13%. If vaccination prevents HPV-positive cancers in both men and women, these figures increase to 25%, 26% and 21%, respectively. In conclusion, if HPV vaccination fully prevents all non-cervical HPV-positive cancers, this would substantially increase its cost-effectiveness. The impact of the vaccination varies depending on the incidence of cervical/non-cervical HPV16/18-positive cancers, the vaccine costs and clinical costs. Observed combinations of these parameters in different countries show a decrease in the CER between 10% and 31%.