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1 Division of Cancer Epidemiology and 2 Department of Pathology, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada; 3 Ludwig Institute for Cancer Research, São Paulo, Brazil; and 4 Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
Requests for reprints: Eduardo L. Franco, Department of Oncology, McGill University, 546 Pine Avenue West, Montreal, Quebec, Canada H2W1S6. Phone: 514-398-8014; Fax: 514-398-5002. E-mail: eduardo.franco{at}mcgill.ca
Background: Besides an established role for certain human papillomavirus (HPV) genotypes in the etiology of cervical cancer, little is known about the influence of multiple-type HPV infections on cervical lesion risk. We studied the association between multiple HPV types and cervical lesions among 2,462 Brazilian women participating in the Ludwig-McGill study group investigation of the natural history of HPVs and cervical neoplasia.
Methods: Cervical specimens were typed by a PCR protocol. The cohort's repeated-measurement design permitted the assessment of the relation between the cumulative and concurrent number of HPV types and any-grade squamous intraepithelial lesions (SIL) and high-grade SIL (HSIL).
Result: At individual visits, 1.9% to 3.2% of the women were infected with multiple HPVs. Cumulatively during the first year and the first 4 years of follow-up, 12.3% and 22.3% were infected with multiple types, respectively. HSIL risk markedly increased with the number of types [odds ratio (OR), 41.5; 95% confidence interval (95% CI), 5.3-323.2 for single-type infections; OR, 91.7; 95% CI, 11.6-728.1 for two to three types; and OR, 424.0; 95% CI, 31.8-5651.8 for four to six types, relative to women consistently HPV-negative during the first year of follow-up]. The excess risks for multiple-type infections remained after exclusion of women infected with HPV-16, with high-risk HPV types, or persistent infections, particularly for any-grade SIL. Coinfections involving HPV-16 and HPV-58 seemed particularly prone to increase risk.
Conclusion: Infections with multiple HPV types seem to act synergistically in cervical carcinogenesis. These findings have implications for the management of cervical lesions and prediction of the outcome of HPV infections. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1274–80)
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