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

• Human papillomavirus (HPV) has been detected in over 90% of all cervical cancers, in 35-70% of anal cancers and in about 10% of tumors of the head and neck. The immune system plays an important role in the manifestation of HPV infections and it is known that organ transplant patients have an increase in HPV associated lesions. Recently, interactions between the p53/Rb suppressor genes, different HPV types and cancer development have been reported. In this study, antibodies towards HPV were monitored before and after transplantation in renal transplant patients in order to see if the antibody response to HPV could be correlated to an increased risk of cervical carcinoma. In a majority of the renal transplant patients the IgG activity to the synthetic peptides L1 (p31) and L2 (p49) derived from the late region of HPV type 16 decreased after transplantation. The IgA activity against HPV type 16 peptide E2 (p245) increased 3-6 months after transplantation in about half of the patients, but declined one year after transplantation. No correlation was 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, HPV serology 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 most pronounced among allogeneic BMT patients which was similar to that obtained for non-latent viruses in the same patient groups. In contrast, it has been reported that antibodies to latent viruses are maintained in long-term surviving BMT patients. Our results suggest that infection with HPV may not always necessarily be latent or persistent. An attempt was made to correlate an ongoing cervical cancer or a history of it with the presence of HPV in peripheral blood cells (PBLs). No HPV DNA (assayed by polymerase chain reaction) was detected in the PBLs of the patients and it was not possible to correlate the presence of HPV in PBLs to disease. The involvement of HPV, EBV and aberrant p53 expression, in squamous cell carcinoma of the head, neck and esophagus, and possible association to prognosis was examined. HPV DNA was identified in approximately 10% of the head and neck tumors. The presence of EBV could not be confirmed in these tumors. Aberrant p53 was detected in approximately half of the tumors. In one HPV type 16 positive tumor, the sequencing of p53 showed that intron 7 was deleted in one of the p53 alleles. Also, overexpression of p53 was found in dysplastic tissue adjacent to HPV negative invasive cancers without aberrant p53 expression. The interpretation of the presence of HPV and aberrant p53 in the tumors could not be correlated to the prognosis of the patients.

Keyword

HPV, immunosuppression, p53, cervical cancer, cancer of the head and neck

Publication and Content Type

vet (subject category)

dok (subject category)