Population-Based Study of Human Papillomavirus Infection and Cervical Neoplasia in Rural Costa Rica

Abstract

To investigate the association of all types of human papillomavirus (HPV) infection with low-grade squamous intraepithelial neoplasia (LSIL), high-grade squamous intraepithelial neoplasia (HSIL), and cancer, the authors conducted a population-based screening of 9175 randomly selected women in rural Costa Rica. Three thousand twenty-four of these women had suspicious findings at screening and were tested for more than 40 types of HPV. In addition to 12 screening-detected cases of cervical cancer, 28 women from throughout Costa Rica who were diagnosed with cervical cancer during the study period were included in the final analyses. The women in this study were 18 to 94 years old (median age = 39 years). Most were multiparous, and only 11 percent had ever smoked. Sexual activity was begun at an average age of 18 years, and more than half had had only one lifetime sexual partner. Overall 16 percent of the women had some kind of HPV infection. Infection rates ranged from 11 percent of those with normal screening results to 89 percent of those with HSIL and 88 percent of those with a diagnosis of cervical cancer. Women with normal cervical cytology had a low rate (4 percent) of infection with cancer-associated HPV types (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68). Only 10 percent of women with atypical squamous cells of undetermined significance (ASCUS) had cancer-associated HPV infection, whereas patients with LSIL, HSIL, and cancer were infected at rates of 54 percent, 80 percent, and 79 percent, respectively (Table 1). In women with normal screening results, the rate of infection with any type of HPV was 20 percent for women under 25 years of age. The infection rate fell as low as 5 percent in middle-aged women but increased to 20 percent for women more than 65 years old. More cancer-associated HPV types than non–cancer-associated HPV types were found in women younger than 25 years, but more non–cancer-associated types than cancer-associated types were found in women older than 55 years. However, women with ASCUS had more cancer-associated HPV types than non–cancer-associated HPV types in both age groups. The prevalence of any type HPV infection in women with ASCUS increased in those who were more than 55 years old. The diagnosis of LSIL was most common in younger women (median age = 29 years) and decreased steadily as age increased. The women with HSIL were older (median age = 34 years). The rate of HPV infection for these women reached a peak of 2.0 percent at age 30 years and then began to decrease. However, a second peak of about 2.0 percent developed at 65 years of age. These older women were the least likely to have ever had cervical screening. Three hundred five women with normal screening results were randomly selected to serve as control subjects in this study. Among this group with normal cytologic findings, there were 26 types of HPV present. Only 1.0 percent of the HPV types found were HPV16 or HPV18. Slightly more than 4 percent of the control group had multiple infections that accounted for 39 percent of the HPV types. HPV16 was the most common HPV type in women with LSIL, HSIL, and cancer (16, 45, and 47 percent, respectively). The presence of HPV16 carried a high risk of developing HSIL (odds ratio [OR] = 320, 95% CI = 97–1000) and an even higher risk of developing cancer (OR = 710, 95% CI = 110–4500). Cancer-associated HPV types were seen in approximately 80 percent of all women with HSIL or cancer (and in 50 percent of the women with LSIL). HPV types 16, 58, 51, and 52 were significantly associated with HSIL, with ORs ranging from 1400 (95% CI = 120–16,000) for HPV16 to 20 (95% CI = 3.8–100) for HPV51. HPV types 16 and 18 were significantly associated with the diagnosis of cancer (OR = 470, 95% CI = 68–3300; OR = 120, 95% CI = 6.7–2200, respectively). J Natl Cancer Inst 2000;92:464–474