Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica

Rolando Herrero, Allan Hildesheim, Conception Bratti, Mark E. Sherman, Martha Hutchinson, Jorge Morales, Ileana Balmaceda, Mitchell D. Greenberg, Mario Alfaro, Robert D. Burk, Sholom Wacholder, Martyn Plummer, Mark Schiffman

Research output: Contribution to journalArticlepeer-review

492 Scopus citations


Background: Human papillomavirus (HPV) is the main cause of cervical neoplasia. Because few population-based studies have investigated the prevalence of type-specific infection in relation to cervical disease, we studied a high-risk population, estimating the prevalence of HPV infection and the risk associated with various HPV types. Methods: We screened 9175 women in Guanacaste, Costa Rica, to obtain a referent standard final diagnosis, and tested 3024 women for more than 40 types of HPV with a polymerase chain reaction-based system. Results: Among women with normal cytology, HPV infections peaked first in women younger than 25 years, and they peaked again at age 55 years or older with predominantly non-cancer- associated types of HPV and uncharacterized HPV types. Low-grade squamous intraepithelial lesions (LSILs) (n = 189) decreased consistently with age. The prevalence of high-grade squamous intraepithelial lesions (HSILs) (n = 128) peaked first around age 30 years and again at age 65 years or older. Seventy-three percent of LSILs were HPV positive, with HPV16 being the predominant type (16% of positive subjects). HPV was found in 89% of HSILs and 88% of cancers, with HPV16 being strongly predominant (51% and 53% of positive subjects). Virtually all HSILs and cancers had cancer-associated HPV types, with high odds ratios (ORs) and attributable fractions around 80%. Risk for HPV16 was particularly high (OR for HSILs = 320, 95% confidence interval [CI] = 97-1000; OR for cancer = 710, 95% CI = 110-4500). Conclusions: We confirm the early decline of HPV infection with age but note increased prevalence after menopause, which could be related to a second peak of HSILs, an observation that warrants further investigation. At least 80% of HPVs involved in cervical carcinogenesis in this population have been characterized. Polyvalent vaccines including the main cancer-associated HPV types may be able to prevent most cases of cervical disease in this region.

Original languageEnglish (US)
Pages (from-to)464-474
Number of pages11
JournalJournal of the National Cancer Institute
Issue number6
StatePublished - Mar 15 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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