Some betapapillomaviruses may contribute to an increased occurrence of squamous cell skin cancer (SCSC) in patients who have undergone organ transplantation. That's according to researchers at Fred Hutchinson Cancer Research Center in Seattle.
Transplant patients routinely receive immunosuppressive therapy to prevent graft rejection. Immunosuppression increases patients' risk of contracting cancers with a viral etiology since the therapy reduces the body's immune response to viruses like human herpesvirus 8, which causes Kaposi’s sarcoma; and the Epstein-Barr virus that causes non-Hodgkin's lymphoma.
Along with the duration and intensity of immunosuppressive therapy, a patient's ethnicity, exposure to the sun and geographic location can also contribute to his or her chances of developing some type of skin cancer following solid organ transplantation.
SCSC is the most frequently occurring cancer in post-transplant patients, but it was not clear if the cancer was associated with a virus. In the study, lead researchers, Drs. Margaret M. Madeleine and Denise A. Galloway, attempted to determine if the prevalence of SCSC in post-transplantation patients could be linked to a specific virus.
Since they are well-established oncogenic viruses, the research team focused on human papillomaviruses (HPV) and polyomaviruses (HPyV). Mucosal HPVs such as HPV16 and HPV18 have been demonstrated to cause cervical, anogenital and oropharyngeal cancers. Cutaneous HPVs are suspected to cause specific kinds of SCSC, and Merkel cell polyomavirus can result in Merkel cell carcinoma.
Additionally, while uncommon, mutations in the TMC6 and TMC8 genes may increase patient susceptibility to HPV infections, thereby increasing the risk of certain HPV pathologies.
To determine if these factors also increased the risk of SCSC in post-transplantation patients, Madeleine and Galloway conducted a nested case-control study.
Researchers focused on 172 patients who developed SCSC following an organ transplant. They tested pretransplant serum for antibodies to determine if the patient had been exposed to various types of HPVs and HPyVs. The serum of 332 control patients was also tested.
The majority of organ transplant patients and control subjects had been exposed to multiple polyomaviruses. Patients with exposure to any of the examined HPyVs did not show an increased risk of SCSC. Those with antibodies to HPV15, HPV20 and HPV36 showed an increased risk of SCSC, but it was not statistically significant.
Those patients who had antibodies to cutaneous papillomaviruses HPV37 or HPV1 did exhibit a higher risk of SCSC than patients with no antibodies present in their serum.
The researchers also looked at TMC genes' affect on patients' development of SCSC. TMC6 and TMC 8 genes from study patients were genotyped, and three TMC8 variants were found to have some association in patients whose serum tested positive for betaHPVs. However, no TMC6 or TMC8 alleles increased the risk of developing SCSC.
The study's findings suggests at least some cutaneous HPVs may increase the risk of SCSC in post organ transplant patients. To further determine the correlation, the researchers plan to conduct another prospective study that will take multiple samples from patients both before and after immunosuppression
