Human papillomavirus (HPV) encompasses over 200 viruses, many spreading through sexual contact. Twelve strains of HPV are considered “high-risk HPV,” and these variants can cause cancer. Alternately, “low-risk HPV” strains can cause less severe health conditions, like warts.
HPVs cause one of the most highly transmitted sexually transmitted infections, leading to millions of cases of anogenital warts annually. Experts have estimated that at least 10% of women worldwide have transmitted an HPV at some point in their lifetime. Luckily, 90% of these infections clear within two years.
However, the link between cancer-causing high-risk HPVs remains significant and has a meaningful impact on the global cancer burden. About 5% of all cancer cases develop from HPV infections, including most cervical and anogenital cancers, as well as some oropharyngeal cancers. Cervical cancers account for over 80% of all HPV-induced cancers, conferring an exceptionally high risk to women.
Scientists remain unclear on the approximately 10% of HPVs that persist and thus raise the risk of cancer in infected women. Strengthening our understanding of the differences in mechanisms underlying HPV infections that persist for more than two years and non-persistent infections could substantially influence the development of new cancer treatments, screening procedures, and prevention strategies.
To add to our current understanding of non-persistent HPV infection in women, a team of researchers investigated the interplay between the virus and the immune system. They recently published their findings in the journal PLOS Biology.
The study (NCT02946346) included 189 women living in Montpellier, France between the ages of 18 and 25. The researchers collected nearly 1,000 samples from the participants, allowing evaluation of viral load, immune cell populations, cytokine expression, and circulating antibody titers. Over the course of follow-up, 76 participants developed a total of 164 HPV infections.
The analysis revealed that the viral load in non-persistent HPV infections plateaus for an average of 13 to 20 months before rapidly clearing. The research identified a subset of T cells called gamma-delta T cells associated with clearance of the HPV infection. T cells make up a diverse group of immune cells involved in protecting from both infection and cancer. Gamma-delta T cells contain a unique subset of T cells capable of directly or indirectly fighting foreign cells. Stress can activate gamma-delta T cells, leading to the production of immune mediators called cytokines that promote clearance of infection. In addition, the researchers found a chemokine called CXCL10 upregulated in cases where HPV infection cleared within two years. CXCL10 plays a vital role in both anti-infection and anti-cancer immunity.
The study demonstrates a strong link between HPV infection and activation of the immune response. These findings could inform public health policy by optimizing personalized screening practices for young women at risk of developing HPV-related cancers. Moreover, the classification of two immune mediators, gamma-delta T cells and CXCL10, provides a compelling rationale for additional studies to develop new drug targets for immune-based therapeutics, sparking a new wave of research and innovation in cancer treatment.
Sources: Int J Cancer, Vaccine, PLOS Biol, Front Immunol
