A PROSPECTIVE-STUDY OF ANTIBODY-RESPONSES TO DEFINED EPITOPES OF HUMAN PAPILLOMAVIRUS (HPV) TYPE-16 IN RELATIONSHIP TO GENITAL AND ANORECTAL PRESENCE OF HPV DNA

The aim of this study was to investigate whether antibody responses ag ainst synthetic peptides derived from genital human papillomavirus (HP V) proteins are associated with laboratory-proven genital and anorecta l HPV infection. In this study, 158 heterosexual patients (110 women a nd 48 men) were followed prospectively. At each visit we collected ser um samples as well as specimens from several sites in the anogenital a rea for detection of HPV type 6/11 (HPV-6/11), -16, -18, and -33 DNAs by PCR. Immunoglobulin A (IgA) and IgG responses against disrupted bov ine papilloma virions and eight different synthetic peptides derived f rom HPV-6/11, -16, and -18 were determined for serum samples from the first and the last visits. The subjects attended the Municipal Sexuall y Transmitted Disease Clinic in Amsterdam, The Netherlands, two to sev en times (mean, four times) at approximately 4-month intervals. Women were monitored over a period of 155 person-years, and men were monitor ed over 65 person-years. The magnitudes of the IgA responses against H PV-16 late protein epitopes L1:13, L1:31, and L2:49 were significantly higher in the sera from the last visit among the currently HPV DNA-po sitive participants than in HPV DNA-negative persons (P = 0.02). When the persons positive for any HPV type at any time during the follow-up period were compared with those who were negative at all times during the follow-up period, we also found a significant elevation of IgA re sponses against L1:31 and L2:49 (P = 0.04 and 0.01, respectively). Whe n the persons who were positive solely for HPV-16 at the last visit we re compared with the currently HPV DNA-negative persons, the sera coll ected at the time of the last visit showed higher IgA titers against t he HPV-16 late protein peptides L1:13, L1:31, and L2:49 in the HPV-16- positive group (P = 0.001, 0.002, and 0.006, respectively). Comparison of the persons who were solely HPV-16 positive at any time during the follow-up period with the participants who were HPV DNA negative duri ng the study period also showed elevations of IgA reactivity to peptid es L1:13 and L2:49 (P = 0.06 and 0.02, respectively). Comparison of op tical density values for sera collected at the first and the last visi ts from a given participant revealed an increase in titers of the last sera. Although the results of the cross-sectional analyses for the fi rst and last visits were not consistent, we concluded that among heter osexual men and women at high risk of HPV infection, IgA antibody tite rs against certain defined HPV-16 late protein epitopes reflect genita l and anorectal HPV infection.