Background The natural history of human papillomavirus (HPV) infections in older women is critical for preventive strategies, including vaccination and screening intervals, but is poorly understood. In a 7-year population-based cohort study in Guanacaste, Costa Rica, we examined whether women's age and the duration of carcinogenic HPV infections influenced subsequent persistence of infection and risk of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse disease. Methods At enrollment, of the 9466 participants eligible for pelvic examination, 9175 were screened for cervical neoplasia using multiple methods; those with CIN 2 or worse disease were censored and treated. Participants at low risk of CIN 2 or worse (n = 6029) were rescreened at 5-7 years (passively followed), whereas higher-risk participants (n = 2115) and subsets of low-risk women (n = 540) and initially sexually inactive women (n = 410) were rescreened annually or semiannually (actively followed) for up to 7 years. HPV testing was done using a polymerase chain reaction-based method. We determined, by four age groups (18-25, 26-33, 34-41, and >/=42 years), the proportion of prevalent infections (found at baseline) and newly detected infections (first found during follow-up) that persisted at successive 1-year time points and calculated absolute risks of CIN 2 and CIN grade 3 (CIN 3) or worse during follow-up. P values are two-sided.

Results Regardless of the woman's age, newly detected infections were associated with very low absolute risks of persistence, CIN 2, or worse disease. For newly detected infections, the rate of progression to CIN 2+ (or CIN 3+), after 3 years of follow-up, was not higher for women aged 34 years and older than for younger women. Moreover, rates of newly detected infections declined sharply with age (in the actively followed group, at ages 18-25, 26-33, 34-41, and >/=42 years, rates were 35.9%, 30.6%, 18.1%, and 13.5%, respectively; P < .001). Among prevalent infections, persistent infections among older women (>/=42 years) was higher than that among younger age groups or new infections at any age (P < .01 for comparison of eight groups). Most (66 of 85) CIN 2 or worse detected during follow-up was associated with prevalent infections. Only a small subset (25 of 1128) of prevalent infections persisted throughout follow-up without apparent CIN 2 or worse.

Conclusions The rate of new infections declines with age, and new infections typically do not progress to CIN 2 or worse disease in older women; thus, overall potential benefit of prophylactic vaccination or frequent HPV screening to prevent or detect new carcinogenic HPV infections at older ages is low.

Determination of the prevalence of type-specific human papillomavirus (HPV) is important for the development of new vaccines and to prevent malignancy. The objective of this study was to determine HPV infection in two areas in the north of Spain, and their evolution in the last 15 years. Between 1991 and 2007, 7,930 fresh cervical swabs were obtained from 5,554 women (37.8 +/- 11.8 years old). From them, 425 have been followed-up for an average of 3.7 +/- 2.08 years after sampling (range 2-14.6), and 71 for 7.7 +/- 2.2 years (range 5-14). Methods based on polymerase chain reaction (PCR) were carried out. Samples from 1,598 (28.8%) women were positive for HPV: 40.9% were under 25 years of age, 34.2% in the 25-35 year age group, 27.2% in the 36-45 year age group, and 19.6% older than 45 years (P < 0.001). HPV was found in 34.4% of the women with cytological alterations versus 23% of women without cervical changes (P < 0.0001). HPV-16 was present in 25.8% of the women, although the study identified 26 different HPV genotypes. After 3 years of follow-up, HPV remained or became undetectable in 87% of the cases, and in 5 years 70.3%. The prevalence of HPV is associated with younger women and women with cytological changes in the cervix. Although HPV-16 is more prevalent, HPV types not included in available vaccines were found the most commonly. The low 3-year (even 5-year) cumulative incidence rate of HPV infection suggests that cervical screening every 3 (or even 5) years is safe and effective. J. Med. Virol. 82:597-604, 2010. (c) 2010 Wiley-Liss, Inc.