Human papillomavirus type 52 polymorphism and high-grade lesions of the uterine cervix

The association between polymorphism of human papillomavirus type 52 (HPV52) and high-grade cervical intraepithelial neoplasia (CIN2,3) was investigated in Canadian women. HPV-52-positive endocervical specimens collected from 216 women selected from a total of 3,614 participants recruited in two case-control and two cohort studies conducted in Canada, were further analyzed by PCR-sequencing of the LCR and E6 gene. Overall, the HPV52 LCR prototype was detected more frequently in Caucasian women (69 of 132, 52.3%, 95% confidence interval (CI): 43.8%-60.6%) than in non-Caucasian women (15 of 48, 31.3%, 95% CI 19.9%-45.4%). In two cohort studies, HPV52 prototype was detected in seven of 15 (46.7%, 95% CI 24.8-69.9) HPV52 persistent infections and 14 of 35 (40.0%, 95% CI 25.5-56.5) transient infections (p = 0.76). In two case-control studies, 30 participants did not have CIN, 18 had low-grade CIN (CIN1), 64 had CIN2,3, seven had cervical cancer and the diagnosis was undefined for 27 women. Variant MTL-52-LCR-02 was detected more frequently in women with cancer (28.6%, 95% CI 7.6%-64.8%) than in women without cancer or CIN2,3 (0%, 95% CI 0.0%-9.2%; p = 0.015). CIN2,3 risk was significantly associated with a deletion at nucleotide position 7695 in the LCR (OR 4.9, 95% CI 1.2-20.8), the T7744C variation in the LCR (OR 5.7, 95% CI 1.1-32.0), and the K93R variation in E6 (OR 6.9, 95% CI 1.3-36.8), after adjusting for age, detection of HPV16 or 18 and study site. These findings indicate that HPV52 polymorphism influences risk of CIN-2,3 and possibly invasive cancer.