Cervical cancer remains the second most common cancer among women worldwide. Certain high-risk strains of the Human Papilloma Virus (HPV) are responsible for causing cervical cancer.
Around 70-90% of individuals with HPV will clear the virus 12 to 24 months after infection. However, in few individuals, the viral infection can persist and cause cellular changes to the cervix that may lead to cervical cancer.
What allows some people to quickly clear the viral infection and others to develop cancer?
Several identified factors may impact an individual’s ability to clear an infection. These include frequent re-infections, immune health, hormone levels, or infections by more than one HPV type.
Genetic factors also play a role. In this article, we explore the relationship between HPV and genetics.
How Do Genes Influence Cancer?
Genes play a role in directing healthy cellular development by controlling cell growth and cell death.
Genes that control how our cells grow, work, and stay alive are called oncogenes. Other genes, called tumor suppressor genes, keep cell growth under control and initiate cell death at the right time. Cancer occurs when DNA mutations alter the genes that turn on oncogenes or turn off tumor suppressor genes, allowing abnormal cellular growth.
Research has found that high-risk HPV contains special proteins called E6 and E7. These proteins turn off tumor suppressor genes. When these genes are deactivated, cells in the cervix can progress and lead to further gene changes and potentially cancer.
Is Cervical Cancer Heritable?
Research suggests that a familial predisposition to cervical cancer may be present.
If your mother or sister had cervical cancer, your chances of developing cervical dysplasia or cancer are increased. Moreover, the risk increases with the increased degree of genetic relatedness.
A Swedish study found that genetic heritability accounted for 27% of the underlying factors for cervical cancer development. The study also tested the role of the environment but found shared environmental factors accounted for only 0-2% of disease progression. The results showed a greater impact than other cancers like colorectal cancer, lung cancer, and melanoma.
The reason for these genetic correlations is not completely understood. It could be explained by a few factors:
- Our genetics may impact our DNA repair pathways associated with CIN3 cervical dysplasia and HPV persistence. Genes have also been associated with supporting viral infection and cell entry.
- Genotypes may influence an individual’s likelihood of exposure to HPV. For example, genetics may influence an individual’s sexual or risk behaviors, thereby influencing the risk level of contracting HPV.
- Genetics may also influence an individual’s cervical cancer risk through HLA alleles. Seven alleles have been associated with cervical cancer, while another four showed a negative association.
- Specific genotypes like BRACA have also been investigated on cervical cancer. It was found that the BRACA1 genotype was associated with a decreased risk of cervical cancer. The same variant is also associated with an increased risk of inherited breast cancer.
Genetics and The Immune System
Cervical cancer may also be driven by genetic factors that influence the immune system, decreasing some women’s ability to fight off infections like HPV.
The immune system is the key factor allowing HPV infections to progress from cervical dysplasia to invasive cancer. The progress from infection to cancer takes several years to decades to develop. The innate and adaptive immune responses are responsible for the regression, persistence, and progression of HPV infections.
For example, women with HPV infections that evolve into high-grade lesions have a reduced immune cellular response. Genetics may also influence the number of immune cells an individual has to defend against infection.
Are you ready to respond to HPV?
MTHFR Genetic Mutation
Some people have a genetic mutation that prevents them from properly converting dietary folate into its active form (5-MTHF) by a process called “methylation”. This mutation may explain why some women with healthy diets and lifestyles struggle to clear the infection.
The MTHFR mutation increases the risk of several diseases including heart disease, colon cancer, and breast cancer. Studies evaluating the association between genetic variants of MTHFR and cervical cancer show some association between the MTHFR C677T polymorphism and CIN 3. However, further studies are needed to determine the actual cause.
An Emerging Field
The research behind genetic predispositions to cervical cancer and cervical dysplasia is very much still evolving. As more research emerges, we may have more clarity as to what leads some to develop more severe reactions to HPV infection than others.