Integration of HPV and the Antibody Respones to HPV Proteins in Patients with Cervical Cancer

Lee, Joon Mo; Kim, Seung Jo; Park, Jong Sup; Namkoong, Sung Eun; Kim, Chan Joo; Park, Tae Chul; Um, Soo Jong

Abstract

PURPOSE
HPV (human papillomavirus) are known as the major causative agent for development of cervical cancer. High-risk HPVs, especially HPV-16 /18 DNA, are often found to be integrated into the human genome in high grade CINs as well as cervial cancer. Investigation of the relationship between the genomic states of HPV genes and their antibody response against the HPV-16 Ll/L2 virus-like particles (VLPs) and the in vitro translated E6 and E7 proteins may help to explain the mechanism of HPV-related cervical carcinogenesis and host immune responses.
MATERIALS AND METHODS
Cervical cancer tissues obtained from 41 patients with cervical cancer were studied by PCR, Southern blot hybridization and the antibody response against HPV-16 Ll/L2 VLPs and HPV-16 E6, E7 proteins of serum were tested by ELISA and radioimmunoprecipitation assay (RIPA), respectively.
RESULTS
Integrated forms of the HPV-16 DNA were found in 23 of the 38 patients (60.5%). The HPV-16 positive cervial cancer patients had a significantly higher prevalence (39.5%; 15/38) of antibodies to HPV-16 Ll/L2 VLPs than 8.7% (2/28) of the the control group (p<0.05). Antibodies to HPV-16 Ll/L2 VLPs were more detectable in 60% (9/15) of the cervical cancer patients with episomal forms of HPV-16 DNA than those who having only integrated HPV-16 (26.1%; 6/23) (p<0.05). Antibodies to E6 and E7 proteins were positive in 36.8% (14/38) and 50% (19/38) of the patients with HPV-16 positive cervical cancer. And those were siginificantly higher than the positivities for the control group (8.3% and 2.8%), (p<0.05). The difference between seroreactivities to E6 and E7 proteins in the patients with episomal forms of HPV-16 DNA (pure episomal and mixed forms) and those with integrated froms of HPV-16 DNA was not significant (P>0.05).
CONCLUSION
Integrated forms of HPV-16 DNA were prevalent in most patients with cervical cancer. Antibodies to HPV-16 Ll/L2 VLPs, in vitro translated HPV-16 E6 and E7 proteins appeared in the significantly larger proportions of the HPV-associated cervical cancer patients than in the controls. Antibodies to HPV-16 Ll/L2 VLPs were more detectable in the cervical cancer patients with episomal form of HPV-16 DNA than those who having only integrated forms of HPV-16. Antibody responses to HPV-16 E6 and E7 proteins were not influenced by the different viral states. More numbers of studies would be necessary to determine the relationship between the genomic states of HPV and the immune responses to their proteins by the such genomic and serologic parameters.