Merkel cell carcinoma is a rare and aggressive skin cancer. Its development is strongly linked to the Merkel cell polyomavirus (MCV), a connection discovered in 2008. This virus is a common component of the microorganisms on the skin of most healthy adults and usually causes no symptoms. In a small fraction of cases, the virus can trigger the events that lead to this cancer.
The Role of the Virus in Merkel Cell Carcinoma
The Merkel cell polyomavirus is present in approximately 80% of Merkel cell carcinoma (MCC) tumors, establishing these as “virus-positive” cases. The development of cancer begins when the virus’s genetic material, its DNA, integrates into the DNA of a human Merkel cell in the skin. This integration is a required event before the tumor cells begin to multiply.
Once integrated, the viral DNA directs the production of its own proteins, known as T antigens. A mutated form of the Large T (LT) antigen and a Small T (sT) antigen are consistently expressed in these cancer cells. The continued production of these viral proteins is necessary for the survival of the MCC tumor cells.
These T antigens function by disrupting the processes that control cell life and death. The LT antigen is known to bind to and inactivate a tumor suppressor protein called the retinoblastoma protein (Rb). When Rb is inactivated by the viral LT antigen, the cell’s braking system on division fails, resulting in uncontrolled cell growth.
The Small T antigen also contributes significantly to the cancer-forming process. It enhances the effects of the LT antigen and promotes the conditions necessary for a cell to become cancerous. Together, these viral proteins override the cell’s natural safeguards, forcing it into a state of continuous division that ultimately gives rise to a tumor. This viral mechanism is distinct from virus-negative MCC, which is instead caused by mutations from factors like ultraviolet light exposure.
Prevalence and Transmission of the Virus
The Merkel cell polyomavirus is widespread. Serological studies indicate that a majority of adults have been exposed to MCV, with most exposures occurring without symptoms. The virus can be detected on the skin of most healthy adults, where it lives as a common member of the skin’s natural microbial community.
This high prevalence demonstrates that infection with MCV is not enough to cause cancer, which is a rare outcome of a common infection. For the virus to trigger cancer, other contributing factors are necessary. These risk factors include advanced age, significant sun exposure, and a weakened immune system.
Individuals with compromised immunity, such as organ transplant recipients or those with HIV, are at a higher risk of developing MCC. A healthy immune system can control the virus and prevent the progression to cancer. The exact route of MCV transmission is not definitively known but is thought to occur through skin-to-skin contact or respiratory droplets.
How Virus Status Affects Prognosis and Treatment
Clinicians can test a Merkel cell carcinoma tumor to determine if it is virus-positive (MCC+) or virus-negative (MCC-). This distinction affects a patient’s likely outcome and treatment plan. Patients with virus-positive tumors have a better prognosis, an outlook directly related to the presence of the viral T antigens within the cancer cells.
The viral T antigens that drive the cancer’s growth also act as an identifier for the immune system. Because these proteins are foreign, they are displayed on the surface of the cancer cells, flagging them as abnormal. This makes the virus-positive cancer cells more recognizable to the body’s immune defenses.
This heightened visibility makes virus-positive MCC responsive to treatments called immune checkpoint inhibitors. These therapies boost the body’s natural immune response against cancer cells. By making the tumor more “foreign-looking,” the virus makes it a better target for these immunotherapies, leading to more effective treatment and improved survival rates.