Skin Cancer Clinical Trial
Official title:
Association of Viral Reactivation and Skin Cancer in Organ Transplant Recipients
Several studies show that the incidence of skin cancer parallels the length and depth of immunosuppression. This study will analyze the correlation of viral reactivation and skin cancer in organ transplant recipients.
Squamous Cell Carcinoma of the skin (SCC) affects people in high numbers worldwide. While a
yearly increase of over 2 million patients, who develop cancer, is recorded, organ
transplant recipients (OTR) have a 60- to 100-fold higher risk of developing skin cancer. In
OTRs, skin cancer is the most frequent tumor that appears, whereas 95% are nonmelanoma skin
cancer cells: squamous cells or basal cell carcinomas. All OTRs need to be treated lifelong
with immunosuppressants in order to prevent the rejection of the transplanted organ.
However, this immunosuppressive treatment leads to a decrease of immunity, and therefore,
cancer cells are able to proliferate easier.
Several studies show that the incidence of skin cancer parallels the length and depth of
immunosuppression. The appearance of CD4 in OTRs with cutaneous carcinomas is significantly
lower compared to those without skin lesions. Various findings have shown a positive
correlation of the period of exposure to immunosuppressants and the risk of skin cancer.
However, little is known about the dose or the type of drug is responsible for skin cancer.
The uptake of three immunosuppressive medicaments compared to the uptake of two results in a
3-fold increased risk of developing cancer. The consequence of the immunosuppressive therapy
is reversible; patients who stop immunosuppressive treatment often show a decrease in skin
cancer. The highest risk for organ rejection is during the first three months after
transplantation. Therefore, an increased dose of immunosuppressors is used during this time.
In addition to cancer, a high increase of viral infections and reactivations is seen in
OTRs. Over 90% of the population carries herpesviruses. The risk of viral infection and
reactivation is much higher in OTRs. While inducing a decrease in immunosurveillance,
herpesvirus can spread easier.
Herpesvirus infections due to the eight human herpes viruses (HHV) are more frequent by
immunosuppression in OTRs. Once a patient is infected with one of the human herpesvirus
types (Herpes simplex viruses 1 and 2, varicella-zoster virus, Epstein-Barr virus, human
cytomegalovirus, human herpesvirus 6 and 7, or Kaposi's sarcoma-associated herpesvirus), the
virus is able to establish a latent, non-productive infection and maintains the capacity for
a life-long reactivation. Due to the decrease of immunity, OTRs are highly susceptible to
activate this latent herpesviral infection, which is a critical aspect of the
immunosuppressive treatment. The risk of the reactivation of Cytomegalovirus and
Epstein-Barr virus in OTRs is much higher compared to the general population.
Taking the above discussed findings together, the investigators hypothesize that viral
infections and reactivations correlate positively with skin cancer in OTRs. Furthermore, the
investigators think that viral reactivation and infection can be used as a marker for a
later incidence of skin cancer. While virus infections and reactivations appear early, OTRs
become affected by SCC in the early and in the late period after the transplantation. The
investigators thus aim to analyze existing data from the STCS and its nested studies to test
these hypotheses: To assess the correlation of viral replication and skin cancer in organ
transplant recipients and to assess viral replication as predictor for skin cancer. The
investigators are interested in all data available from other studies of the STCS and to
divide all organ transplant recipients e.g. for CMV in four groups: no replication, a larger
group who show asymptomatic viral replication, some of them with viral syndrome and the ones
with proven disease.
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Observational Model: Cohort, Time Perspective: Retrospective
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