What’s New in Oral Cavity and Oropharyngeal Cancer Research?

Research on oral and oropharyngeal cancers is being done in many university hospitals, medical centers, and other institutions worldwide . Each year, scientists find out more about what causes these diseases, how to prevent them, and how to better treat them. Most experts agree that treatment in a clinical trial should be considered for any type or stage of cancer in the head and neck areas. This way people can get the best treatment available now and may also get the new treatments that are thought to be even better.

DNA changes in oral cavity and oropharyngeal cancers

A great deal of research is being done to learn about the DNA changes that cause the cells in the oral cavity and oropharynx to become cancer.

More than half  of all head and neck cancers have mutations of the PIK3CA oncogene. This can cause cells to grow out of control which can lead to cancer. Drugs that target the protein, called PI3K, made by the abnormal PIK3CA gene are already approved for use to treat other cancers, such as breast cancer.  Studies are being done to see if similar targeted therapy drugs will work in head and neck cancer, especially HPV-positive cancers because they tend to make too many copies of the PIK3CA oncogene. 

One of the changes often found in DNA of oral cavity and oropharyngeal cancer cells, especially HPV-negative cancer cells, is a mutation of the TP53 gene. The protein produced by this gene (called p53) normally helps keep cells from growing too much and helps to destroy cells that are too damaged to be fixed. Changes in the TP53 gene can lead to increased growth of abnormal cells and cancer.

Some studies suggest that tests to find these gene changes might help find oral and oropharyngeal cancers early. These tests may also be used to better find cancer cells that might have been left behind after surgery and to determine which tumors are most likely to respond to chemo or radiation therapy. The use of p53 gene therapy as a treatment for these cancers is also being studied in early-phase clinical trials.

Discoveries about how changes in the DNA of cells in the mouth and throat cause these cells to become cancer are also being applied to experimental treatments intended to reverse these changes. Another type of gene therapy boosts the immune system so it can better find and kill cancer cells. These forms of treatment are still in very early stages of study, so it will be several years before we know if any of them are effective.

Screening and early detection of oral cavity and oropharyngeal cancers

Looking for HPV infection has become a part of screening tests for cervical cancer over the years. Given the rise in HPV-positive head and neck cancers, especially in the oropharynx, some studies are looking at ways to screen for HPV infection in the oral cavity and oropharynx as there is no FDA approved test right now for this. Other studies are checking to see if blood tests might identify people with the high-risk types of HPV infection and if this is something that can be used as a screening tool for HPV-positive oropharyngeal cancer. This might help prevent or catch these cancers early.

Cancers of the head and neck can be hard to find early. And almost half of all oral cavity and oropharyngeal cancers have already spread to the lymph nodes when they are first diagnosed. Given these issues, research is being done to find ways to detect it more easily and hopefully sooner. For example, one study tested the air people breathe out (exhale) for certain chemicals that seem to be linked with cancer of the head and neck area.

Treatment of oral cavity and oropharyngeal cancers

Oral cavity and oropharyngeal cancers that are linked with HPV tend to have a better outcome than those that are HPV-negative. Clinical trials are starting to look at these HPV-positive and HPV-negative cancers separately. For instance, studies are being done to see if HPV-positive cancers can be treated with less chemotherapy and/or radiation without reducing survival. Researchers are also working on treatments aimed at HPV infections or that target HPV-infected cancer cells. Studies are also looking for better ways to treat HPV-negative cancers, too, as well as the best ways to use the treatments we already have.

A great deal of research is focused on improving results from chemotherapy (chemo) for people with these cancers. This includes figuring out which combinations of drugs work best and determining how best to use these drugs along with other forms of treatment. Researchers also continue to develop new chemo drugs that might be more effective against advanced oral and oropharyngeal cancers. They're also looking at whether drugs approved to treat other types of cancer might work for these cancers.

Doctors are always looking at newer ways of focusing radiation on tumors more precisely to help them get more radiation to the tumor while limiting side effects to nearby areas. This is especially important for head and neck tumors like oral cavity and oropharyngeal cancers, where there are often many important structures very close to the tumor.

Clinical trials are studying targeted drug therapies that might block the action of substances (such as growth factors and growth factor receptors) that cause head and neck cancers to grow and spread. Some targeted drugs are being studied that block the ability of the cancer cell to keep growing and help chemoradiation work better.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Boscolo-Rizzo P, Furlan C, Lupato V, Polesel J, Fratta E. Novel insights into epigenetic drivers of oropharyngeal squamous cell carcinoma: role of HPV and lifestyle factors. Clin Epigenetics. 2017;9:124.

Bourhis J, Sun XS, Le Tourneau C, et al; GORTEC Investigators. 3-year follow-up results of the double-blind, randomized phase II trial comparing concurrent high-dose cisplatin chemoradiation plus xevinapant (Debio 1143) or placebo in high-risk patients with locally advanced squamous cell carcinoma of the head and neck. Presented at: 2020 European Society for Clinical Oncology Virtual Congress; September 19-21, 2020; virtual. LBA39.

Cheraghlou S, Yu PK, Otremba MD, et al. Treatment deintensification in human papillomavirus-positive oropharynx cancer: Outcomes from the National Cancer Data Base. Cancer. 2018;124(4):717-726.

Dharmawardana N, Goddard T, Woods C, Watson DI, Ooi EH, Yazbeck R. Development of a non-invasive exhaled breath test for the diagnosis of head and neck cancer [published online ahead of print, 2020 Sep 9]. Br J Cancer. 2020;10.1038/s41416-020-01051-9. doi:10.1038/s41416-020-01051-9.

Dunn LA, Fury MG, Sherman EJ, et al. Phase I study of induction chemotherapy with afatinib, ribavirin, and weekly carboplatin and paclitaxel for stage IVA/IVB human papillomavirus-associated oropharyngeal squamous cell cancer. Head Neck. 2018;40(2):233-241.

García-Escudero R, Segrelles C, Dueñas M, et al. Overexpression of PIK3CA in head and neck squamous cell carcinoma is associated with poor outcome and activation of the YAP pathway. Oral Oncol. 2018;79:55-63. doi:10.1016/j.oraloncology.2018.02.014.

Huang SH, O'Sullivan B, Waldron J. The Current State of Biological and Clinical Implications of Human Papillomavirus-Related Oropharyngeal Cancer. Semin Radiat Oncol. 2018;28(1):17-26.

SEER Cancer Stat Facts: Oral Cavity and Pharynx Cancer. National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/statfacts/html/oralcav.html

References

Boscolo-Rizzo P, Furlan C, Lupato V, Polesel J, Fratta E. Novel insights into epigenetic drivers of oropharyngeal squamous cell carcinoma: role of HPV and lifestyle factors. Clin Epigenetics. 2017;9:124.

Bourhis J, Sun XS, Le Tourneau C, et al; GORTEC Investigators. 3-year follow-up results of the double-blind, randomized phase II trial comparing concurrent high-dose cisplatin chemoradiation plus xevinapant (Debio 1143) or placebo in high-risk patients with locally advanced squamous cell carcinoma of the head and neck. Presented at: 2020 European Society for Clinical Oncology Virtual Congress; September 19-21, 2020; virtual. LBA39.

Cheraghlou S, Yu PK, Otremba MD, et al. Treatment deintensification in human papillomavirus-positive oropharynx cancer: Outcomes from the National Cancer Data Base. Cancer. 2018;124(4):717-726.

Dharmawardana N, Goddard T, Woods C, Watson DI, Ooi EH, Yazbeck R. Development of a non-invasive exhaled breath test for the diagnosis of head and neck cancer [published online ahead of print, 2020 Sep 9]. Br J Cancer. 2020;10.1038/s41416-020-01051-9. doi:10.1038/s41416-020-01051-9.

Dunn LA, Fury MG, Sherman EJ, et al. Phase I study of induction chemotherapy with afatinib, ribavirin, and weekly carboplatin and paclitaxel for stage IVA/IVB human papillomavirus-associated oropharyngeal squamous cell cancer. Head Neck. 2018;40(2):233-241.

García-Escudero R, Segrelles C, Dueñas M, et al. Overexpression of PIK3CA in head and neck squamous cell carcinoma is associated with poor outcome and activation of the YAP pathway. Oral Oncol. 2018;79:55-63. doi:10.1016/j.oraloncology.2018.02.014.

Huang SH, O'Sullivan B, Waldron J. The Current State of Biological and Clinical Implications of Human Papillomavirus-Related Oropharyngeal Cancer. Semin Radiat Oncol. 2018;28(1):17-26.

SEER Cancer Stat Facts: Oral Cavity and Pharynx Cancer. National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/statfacts/html/oralcav.html

Last Revised: March 23, 2021

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