Asian-American variants of human papillomavirus 16 and risk for cervical cancer: a case-control study

Human papillomavirus 16 (HPV16) has a number of variants, each with a diffe rent geographic distribution and some that are associated more often with i nvasive neoplasias. We investigated whether the high incidence of cervical cancer in Mexico (50 cases per 100 000 women) may be associated with a high prevalence of oncogenic HPV16 variants. Methods: Cervical samples were col lected from 181 case patients with cervical cancer and from 181 age-matched control subjects, all from Mexico City. HPV16 was detected with an E6/E7 g ene-specific polymerase chain reaction, and variant HPV classes and subclas ses were identified by sequencing regions of the E6 and L1/MY genes. Clinic al data and data on tumor characteristics were also collected. All statisti cal tests were two-sided. Results: HPV16 was detected in cervical scrapes f rom 50.8% (92 of 181) of case patients and from 11% (20 of 181) of control subjects. All HPV16-positive samples, except one, contained European (E) or Asian-American (AA) variants. AA and E variants were found statistically s ignificantly more often in case patients (AA = 23.2% [42 of 181]; E = 27.1% [49 of 181]) than in control subjects (AA = 1.1% [two of 181]; E = 10% [18 of 181]) (P < .001 for case versus control subjects for either E or AA var iants, chi (2) test). However, the frequency of AA variants was 21 times hi gher in cancer patients than in control subjects, whereas that ratio for E variants was only 2.7 (P = .006, chi (2) test). The odds ratio (OR) for cer vical cancer associated with AA variants (OR = 27.0; 95% confidence interva l [CI] = 6.4 to 113.7) was higher than that associated with E variants (OR = 3.4; 95% CI = 1.9 to 6.0). AA-positive case patients (46.2 +/- 12.5 years [mean +/- standard deviation]) were 7.7 years younger than E-positive case patients (53.9 +/- 12.2 years) (P = .004, Student's t test). AA variants w ere associated with squamous cell carcinomas and adenocarcinomas, but E var iants were associated with only squamous cell carcinomas (P = .014, Fisher' s exact test). Conclusions: The high frequency of HPV16 AA variants, which appear to be more oncogenic than E variants, might contribute to the high i ncidence of cervical cancer in Mexico.