Human papillomavirus (HPV) can have a domino effect on a person’s health. Some types can cause genital warts and infections that lead to cell changes on the surface of a woman’s cervix (if not cervical cancer itself). These lesions, called cervical dysplasias, can also lead to complications.

Dysplasias come in three grades depending on how difficult they are to treat. Experts believe that the toughest lesions, in grade three, are most likely to cause anogenital cancer — an umbrella term for anal, vulvar, and vaginal cancers. But according to the authors of a new study published in Cancer, Epidemiology Biomarkers & Prevention, the studies that have examined this potential link suffer from small sample sizes, limited follow-up time, and a lack of adjustment for potential confounding factors. To fill in the gap, they looked at 34 years of data on nearly 3 million women. And it turns out, women with HPV are at risk for more than cervical cancer.

The women were registered with the Danish Cancer Registry, making it easy for researchers to access details about precancerous conditions and cancer types they might have suffered. For information on any cell changes that would indicate dysplasia, researchers also looked at data collected by the Pathology Data Bank.

Results showed that women with second- and third-grade dysplasia were more likely to develop cancer than women with no history of the condition. Those with second-grade lesions were 2.9 more likely to develop anal cancer, 2.5 times more likely to develop vulvar cancer, and 8.1 times more likely to develop vaginal cancer. These risks roughly doubled in women with third-grade infections. Cancer risk was highest the first year after women were diagnosed, but the researchers found this risk persisted for 25 years or more.

While the risk of cervical cancer is relatively well known, the study’s findings suggest that women with HPV are at long-lasting risk for anogenital cancers too. Lead study author Susanne Krüger Kjær believes that preventing HPV infection from occurring in the first place may be the best way to drive down subsequent cancer rates.

“We had thought that perhaps the women with [third-grade dysplasia] were the ones who were being treated by doctors and, therefore, receiving more examinations and consequently getting diagnosed with other cancers,” Kjær, a professor of gynecological cancer epidemiology at the Danish Cancer Society Research Center, said in a press release. But given the years-long risk, she doesn’t think high cancer rates are a result of more regular doctor’s appointments and the extra attention they bring.

The study may also offer new insight into the genital infections that HPV sometimes causes. Prior studies have shown both women and men with HPV face an increased risk of genital infection, possibly due to an "inadequate immune response."And even if the dysplasias resulting from infection are treated, the researchers suspect HPV may still be present in the anogenital region and could be behind patients' long-term risk for cancer.

Source: Kjaer SK, et al. Long-Term Risk for Noncervical Anogenital Cancer in Women with Previously Diagnosed High-Grade Cervical Intraepithelial Neoplasia: A Danish Nationwide Cohort Study. Cancer, Epidemiology Biomarkers & Prevention. 2016.