title: Relationships of human papillomavirus type, qualitative viral load, and age with cytologic abnormality.
abstract: Persistent cervical infections with carcinogenic human papillomaviruses (HPV) cause virtually all cervical cancer. Cytologic abnormalities are the manifestations of HPV infections used to identify women at risk. To compare the potential of the full range of anogenital HPV genotypes to induce cytopathic effects, we examined the influences of HPV type, viral load, and age on cytopathology among 1,222 women having a single HPV type at enrollment into a 10,000-woman population-based study in Costa Rica. Cervical specimens were tested for approximately 40 HPV types by MY09/MY11 L1 primer PCR and type-specific dot blot hybridization. Types were organized by phylogenetic species and cancer risk. PCR signal strength served as a qualitative surrogate for viral load. Overall, 24.8% [95% confidence interval (95% CI), 22.4-27.3] of single prevalent HPV infections had concurrent abnormalities (atypical squamous cells or worse) ranging from 0.0% to 80.0% based on HPV type. Noncarcinogenic alpha3/alpha15 types, although highly prevalent, uncommonly caused cytologic abnormalities (13.1%; 95% CI, 9.8-17.0). In contrast, one quarter to nearly one half of infections with a single major carcinogenic species type (alpha9/alpha11/alpha7/alpha5/alpha6) produced abnormalities. Greater abnormalities were observed with increasing qualitative viral load of carcinogenic types; fewer abnormalities were observed among older women (>54 years). A high percentage (46.2%) of detected abnormalities in women infected with HPV16 or related alpha9 types were high grade or worse, consistent with strong carcinogenicity, compared with 10.7% in women infected with alpha7 types, including HPV18, a major cause of adenocarcinoma. The lack of evident severe abnormalities associated with HPV18 and related HPV types might have implications for screening for poorly detected glandular and alpha7-related lesions.
authors.affiliation: Division of Cancer Epidemiology and Genetics and Cancer Prevention Fellowship Program, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. kovacicm@mail.nih.gov
authors.forename: Melinda Butsch
authors.initials: MB
authors.lastname: Kovacic
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Ana C
authors.initials: AC
authors.lastname: Rodriguez
authors.forename: Martha L
authors.initials: ML
authors.lastname: Hutchinson
authors.forename: M Concepción
authors.initials: MC
authors.lastname: Bratti
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Jorge
authors.initials: J
authors.lastname: Morales
authors.forename: Mario
authors.initials: M
authors.lastname: Alfaro
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burk
mesh_terms: D000328:Adult; D000367:Age Factors; D002584:Cervix Uteri / Q000473:pathology / Q000821:virology; D015331:Cohort Studies; D003364:Costa Rica / Q000453:epidemiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000145:classification* / Q000235:genetics; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000473:pathology* / Q000821:virology*; D002577:Uterine Cervical Diseases / Q000453:epidemiology / Q000473:pathology* / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000821:virology; D019562:Viral Load; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000821:virology