Infection with HPV 16 or HPV 18 variants and risk of low-grade squamous intraepithelial lesions in young women

H Richardson PhD^a,b, F Coutlée MD^e, M Abrahamowicz PhD^b, P Tellier MD^c, G Kelsall MA^a,c, H Voyer BSc^e, A Ferenczy MD^a,d, EL Franco PhD^a,b

^aDepartment of Oncology, ^bEpidemiology & Biostatistics, ^cFamily Medicine, ^dPathology; McGill University, Montreal, Canada, ^eLaboratoire de Virologie Moleculaire, Centre de Recherche et Departement de Microbiologie et Infectiologie, Hôpital Notre-Dame du Centre Hospitalier de l’Université de Montréal, Montreal, Canada

Aim: The objectives of this study were to evaluate the association between infections with European (E) or Non-European (NE) variants of HPV 16 or HPV 18, and newly acquired low-grade squamous intraepithelial lesions (LSIL), in a cohort of university students. Methods: Female university students (n=621) in Montreal were followed for 24 months at 6-month intervals. At each visit a cervical cell specimen was collected. HPV DNA was detected using the MY09/MY11 PCR protocol and 27 HPV genotypes were identified by the line blot assay (Roche Molecular Systems Inc.). Clinical samples that were positive for HPV types 16 or 18 were analyzed for HPV 16 and 18 variants. A PCR-sequencing method was used with specific HPV-16 and HPV-18 primers designed to flank nucleotide positions 7478-7841 and 7485-7805, respectively, in the viral genome's long control region. Variants were classified into two groups: European (E) or Non-European (NE). Logistic regression was used to evaluate the association between an incident LSIL infection and HPV status. The Kaplan-Meier technique was used to estimate the cumulative probability of acquiring or clearing an LSIL according to LR- or HR-HPV types or HPV16/18 variant status. Results: The overall incidence rate for LSIL among women in the cohort was 2.4 per 100 person-years, and was 4.1 per 100 person-years among women with HPV. Women with an NE variant (OR=38.1 95% CI: 4.7, 310.9) or an E variant infection (OR=10.6 95% CI: 2.1, 52.4) were significantly more likely to have an incident LSIL compared to women who were HPV negative. Conclusion: This study suggests that intratype variability in HPV 16 or -18 may mediate LSIL development and Non-European variants may be more strongly associated with incident LSIL than European variants.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 897 (Precursor lesions).