Long-term outcomes of high-risk human papillomavirus infection support a long interval of cervical cancer screening

Knowing that infection of high-risk human papillomavirus (HPV) causes virtually all cervical cancer (CC), the long-term outcomes of HPV infection, especially the absolute risk and time lapse of developing CC, are beyond the scope of ordinary follow-up study owing to ethical concerns. The present study followed the natural history and long-term outcomes of HPV infection in a cohort of women by national health insurance care and data linkage without additional disturbance. The status of cervical HPV infection was determined in 1708 healthy women, aged 20–90 (median 43), enrolled from 10 hospitals in seven cities around the island country of Taiwan. Records of consecutive Pap smear results and cancer reports of 108 cytology-negative, HPV-positive and 1202 cytology- and HPV-negative women with no prior record of CC or abnormal cervical cytology were retrospectively analysed for a duration of up to 75 months (median 61 months). The cumulative incidences of high-grade squamous intraepithelial lesion (HSIL) and in situ/invasive cancer in HPV-positive women were 5.6 and 3.7%, respectively, and those in HPV-negative women were 0.3 and 0%. After adjusting for other risk factors, HPV-positive subjects had 24.9 (95% CI: 7.0–108.3; P<0.0001) folds of risk of developing HSIL or above cervical neoplasia as compared to HPV-negative subjects, whereas risk for low-grade intraepithelial lesion and atypical squamous cytology was not increased. The study showed that women with a prevalent infection of high-risk HPV had a 4% cumulative risk for CC in 6 years, whereas those tested negative had little risk. The result supports an HPV test-orientated CC screening programme with intervals of at least 5 years.