Relationships of human papillomavirus type, qualitative viral load, and age with cytologic abnormality.
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.
Kovacic
Melinda Butsch
MB
Division of Cancer Epidemiology and Genetics and Cancer Prevention Fellowship Program, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. kovacicm@mail.nih.gov
Castle
Philip E
PE
Herrero
Rolando
R
Schiffman
Mark
M
Sherman
Mark E
ME
Wacholder
Sholom
S
Rodriguez
Ana C
AC
Hutchinson
Martha L
ML
Bratti
M Concepción
MC
Hildesheim
Allan
A
Morales
Jorge
J
Alfaro
Mario
M
Burk
Robert D
RD
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