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Relationships of Human Papillomavirus Type, Qualitative Viral Load, and Age with Cytologic Abnormality

¹ Division of Cancer Epidemiology and Genetics and ² Cancer Prevention Fellowship Program, National Cancer Institute, NIH, Bethesda, Maryland; ³ Proyecto Epidemiológico Guanacaste; ⁴ Laboratorio Nacional de Citología, Caja Costarricense de Seguro Social, San Jose, Costa Rica; ⁵ Women and Infants' Hospital, Providence, Rhode Island; and ⁶ Albert Einstein College of Medicine, Bronx, New York

Requests for reprints: Melinda Butsch Kovacic, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Suite 550, EPS MSC 7234, Bethesda, MD 20892-7234. Phone: 301-496-1692; Fax: 301-402-0916; E-mail: kovacicm{at}mail.nih.gov.

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 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 3/15 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 (9/11/7/5/6) 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 9 types were high grade or worse, consistent with strong carcinogenicity, compared with 10.7% in women infected with 7 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 7-related lesions. (Cancer Res 2006; 66(20): 10112-9)

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