Antibodies against linear and conformational epitopes of human papillomavirus type 16 that independently associate with incident cervical cancer

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Abstract
In a seroepidemiological study of incident cervical cancer, 94 cases and 188 population‐based controls were used to evaluate the disease‐association of IgG and IgA antibody responses against 6 human papillomavirus (HPV) type‐16 antigens. Nine of the tested antibody responses were positively associated with cervical cancer, with odds ratios (ORs) ranging from 2.5 to 15.0. The antibody responses most strongly associated with cervical cancer were IgA against E6:10, an epitope derived from the carboxyterminal part of the HPV16 E6 [OR = 15.0, confidence intervals (CI) = 5.9–48.6], IgG against HPV16 virus‐like particles (OR = 9.5, CI = 3.9‐28.0) and IgG against the EI:19 epitope in the middle part of the EI protein of HPV16 (OR = 7.7, CI = 3.9–16.5). When the 3 serological assays that showed the strongest association with cervical cancer were combined, positivity for 2 assays was found among 52% of cases at an OR of 29.9. We conclude that antibody responses to several linear and conformational HPV epitopes are independently associated with cervical cancer and that combined analysis of several HPV antibody responses can result in better predictive values for HPV‐associated cancer.