Studies on infections with human papillomavirus (HPV) in immunosuppressed patients and patients with HPV related tumors

Abstract: From the Department of Immunology, Microbiology, Pathology and Infectious Diseases, Division ofClinical Virology, Karolinska Institutet, Huddinge Hospital, S-141 86 Huddinge, SwedenStudies on Infections with Human Papillomavirus (HPV) in ImmunosuppressedPatients and Patients with HPV Related Tumors Human papillomavirus (HPV) has been detected in over 90% of all cervical cancers, in 35-70% ofanal cancers and in about 10% of tumors of the head and neck. The immune system plays animportant role in the manifestation of HPV infections and it is known that organ transplant patientshave an increase in HPV associated lesions. Recently, interactions between the p53/Rb suppressorgenes, different HPV types and cancer development have been reported. In this study, antibodies towards HPV were monitored before and after transplantation in renaltransplant patients in order to see if the antibody response to HPV could be correlated to an increasedrisk of cervical carcinoma. In a majority of the renal transplant patients the IgG activity to the syntheticpeptides L1 (p31) and L2 (p49) derived from the late region of HPV type 16 decreased aftertransplantation. The IgA activity against HPV type 16 peptide E2 (p245) increased 3-6 months aftertransplantation in about half of the patients, but declined one year after transplantation. No correlationwas found between the antibody kinetics towards HPV and an increased risk of cervical carcinoma. To study HPV infection in long term surviving bone marrow transplant (BMT) patients, HPVserology was monitored before and after BMT. The IgG activity against HPV type 16 L1 (p31) andL2 (p49) peptides was found to decline one year after transplantation. The decline was mostpronounced among allogeneic BMT patients which was similar to that obtained for non-latent virusesin the same patient groups. In contrast, it has been reported that antibodies to latent viruses aremaintained in long-term surviving BMT patients. Our results suggest that infection with HPV may notalways necessarily be latent or persistent. An attempt was made to correlate an ongoing cervical cancer or a history of it with the presence ofHPV in peripheral blood cells (PBLs). No HPV DNA (assayed by polymerase chain reaction) wasdetected in the PBLs of the patients and it was not possible to correlate the presence of HPV in PBLsto disease. The involvement of HPV, EBV and aberrant p53 expression, in squamous cell carcinoma of thehead, neck and esophagus, and possible association to prognosis was examined. HPV DNA wasidentified in approximately 10% of the head and neck tumors. The presence of EBV could not beconfirmed in these tumors. Aberrant p53 was detected in approximately half of the tumors. In oneHPV type 16 positive tumor, the sequencing of p53 showed that intron 7 was deleted in one of thep53 alleles. Also, overexpression of p53 was found in dysplastic tissue adjacent to HPV negativeinvasive cancers without aberrant p53 expression. The interpretation of the presence of HPV andaberrant p53 in the tumors could not be correlated to the prognosis of the patients.Key words: HPV, immunosuppression, p53, cervical cancer, cancer of the head and neck