UW study details how HPV may promote head and neck cancer

April 12, 2023

Cancer researchers have long known that the sexually transmitted human papillomavirus (HPV) is a leading cause of head and neck cancer and now a study from the University of Wisconsin School of Medicine and Public Health sheds light on how HPV turns healthy cells into cancer.

Dr. Pippa Cosper, assistant professor of human oncology, UW School of Medicine and Public Health, focuses her research on how HPV infection affects cell function. When she looked through the microscope at tumor cells from patients with HPV-positive head and neck cancer, she noticed “a striking difference” compared to cells from HPV-negative tumors, she said.

“The HPV-infected cells had a distinct abnormality when they were dividing,” Cosper said.

When a normal cell divides, the chromosomes line up neatly in the middle before the cell splits into two identical daughter cells. But the HPV-positive tumor cells had chromosomes that were stuck at the ends of the cell, meaning that they would not distribute to daughter cells correctly. This resulted in cells with abnormal chromosome content, which is a hallmark of cancer, according to Cosper.

“One daughter cell may get an extra copy of one or more chromosomes and the other daughter cell may lose those copies,’’ she said. “That is called chromosomal instability.”

Cosper’s team created a model to study this further using normal oral tissue cells by making them express specific viral proteins encoded by the HPV virus. They found that an HPV protein called E6 causes chromosomes to be stuck at the spindle pole by degrading a large protein, CENP-E, which in a normal cell guides the chromosomes to line up and divide evenly.

“We showed in cells derived from tumors and in cell line models that the viral protein E6 causes degradation of CENP-E resulting in this type of chromosome missegregation,’’ Cosper said. “We also showed this is true in HPV-positive cervical cancer cells.”

Polar chromosomes
A normal oral keratinocyte expressing HPV oncogene E6, causing polar chromosomes.

This chromosome shuffling could grant growth and survival advantages to some cells, which likely contributes to the development of cancer. Therefore, the UW research team thinks this is an important step in how HPV infection leads to tumor formation.

The study was published in the Proceedings of the National Academy of Sciences and was under the guidance of the study’s senior author, Beth Weaver, who has a doctorate in biomedical sciences and is a professor of cell and regenerative biology at the UW School of Medicine and Public Health.

The most common sexually transmitted infection in the United States is HPV, and it causes 70% of head and neck cancers in the oropharynx, 90% of anal cancers and almost all cervical cancers, according to the National Cancer Institute.

“The good news is we have a vaccine against HPV, which protects against the nine major types of HPV that cause cancer,” Cosper said.

However, only 55 to 60% of people have received this vaccine in the U.S., according to Cosper.

The U.S. Food and Drug Administration approved the use of Gardasil, an HPV vaccine, for all genders ages 9 to 45. Two doses of the HPV vaccine are recommended for children ages 11 or 12.

“I really urge people to get this vaccine and get this vaccine for your child, it could save their life,” Cosper said.

Cosper is also a physician-scientist in radiation oncology who treats cancer patients at UW Health Johnson Creek Cancer Center. In the laboratory, her research investigates ways to exploit a cancer cell’s inherent defects during division to promote cell death, which could lead to tumor regression. She is currently working on how chromosomal instability affects a cancer cell’s sensitivity to radiation.

The goal of this ongoing research is to discover biomarkers that could create more personalized treatment for head and neck cancer patients, she said.

Other members of the UW Carbone Cancer Center involved in the study include Randall Kimple and Paul Lambert; other UW researchers on the paper are Laura Hrycyniak, Maha Paracha, Denis Lee, Jun Wan, Kathryn Jones, Sophie Bice and Kwangok Nickel.

This research received support from the University of Wisconsin Translational Research Initiatives in Pathology laboratory which is supported by the UW Department of Pathology and Laboratory Medicine and NIH S10 OD023526 for use of its facilities and services. It also was supported in part by NIH P50DE026787 (DRP to B.A.W.) and P50CA278595 (pathology core), R01CA234904 (B.A.W.), T32CA009135 (L.F.H.), K08CA256166 (P.F.C.), P01CA022443 (D.L.L. and P.F.L.), R35CA210807 (D.L.L. and P.F.L.), the University of Wisconsin Carbone Cancer Center Support Grant P30CA014520, which supports the University of Wisconsin Carbone Cancer Center BioBank, the Radiological Society of North America (Research Fellow Grant RF1904 to P.F.C.), and the American Society of Clinical Oncology (Young Investigator Award to P.F.C.).