Mysterious Cancers of 'Unknown' Origin in Men Traced Back to HPV

A doctor palpates a man's throat
(Image credit: wavebreakmedia/

Some cancers are mysterious, in that doctors cannot determine where they originate and how they will spread. These cancers often are given the unwieldy name "unknown primary squamous cell carcinoma" (UPSCC).

About 4 percent of head and neck cancers are of the UPSCC variety. They may appear in this area of the body, having metastasized or spread from elsewhere, but the specific origin of the cancer cells is not clear. And this lack of knowledge of the cancer type tends to make the cancer harder to treat.

Now, researchers at Johns Hopkins School of Medicine in Baltimore have found that the human papillomavirus (HPV) is strongly associated with UPSCCs in the head and neck area and, more specifically, cancer of the oropharynx, the middle part of the throat that includes the tonsils and the base of the tongue.

The finding may help turn the "unknown" in UPSCC into a "known" and help doctors zero in on a treatment option and targeted therapy, the researchers said. Also, the discovery bolsters the theory that rising rates of HPV infection are driving an increased frequency of not only oropharynx or "throat" cancers but also UPSCCs — further highlighting the importance of vaccinating against HPV infection.

The study appears today (Jan. 14) in the journal JAMA Otolaryngology–Head & Neck Surgery.

HPV is primarily a sexually transmitted virus. Most infections will cause no harm. However, HPV is the main cause of cervical cancer and is responsible for nearly 300,000 deaths worldwide annually, according to the World Health Organization.

HPV — along with heavy tobacco and alcohol use — is also a major cause of throat cancer, particularly in men. This fact went mainstream in 2013, when actor Michael Douglas implied his throat cancer was caused by HPV. (Douglas has since described the cancer as being on his tongue, but the cause is not known; he also was a heavy drinker.)

About 75 percent of the estimated 12,500 yearly cases of throat cancer in the United States are caused by HPV, according to the Centers for Disease Control and Prevention. [Top 10 Cancer-Fighting Foods]

HPV also causes cancers of the anus, penis, vulva and vagina. The reason appears to be that the virus resides in both the genital and oropharyngeal areas, and can be spread through anal, vaginal or oral sex. Doctors recommend that teenagers, both female and male, receive the HPV vaccine before they become sexually active.

In the new study, Dr. Carole Fakhry, an associate professor of otolaryngology – head and neck surgery at Johns Hopkins School of Medicine, led a research team that examined 84 patients, mostly male, with UPSCC over the course of 9.5 years — the largest study of its kind at a single hospital. They found that more than 90 percent of the patients were HPV-positive, indicating that HPV was a probable cause of the cancer.

For nearly 60 percent of the patients with these "unknown" cancers, Fakhry's team found that they could eventually identify the tumor's primary source. All of these cancers were in the oropharynx, either in the base of the tongue or in the tonsils, thus changing the murky UPSCC diagnosis to oropharyngeal cancer with the promise of a better prognosis.

"Localization allows for more targeted therapy and potentially decreased morbidity and improved survival," the researchers wrote in their paper.

The researchers also documented a steady rise in the number of UPSCC cases seen at Johns Hopkins Hospital: In the first four years of the study, there were 14 cases of UPSCC; in the next three years, there were 30 cases; and over the next 2.5 years, there were 37 cases. This increase mirrors the national trend of rising HPV infection rates among young people.

The study "gives us a glimpse of what is happening at other hospitals," said Fakhry, who emphasized the importance for teenagers to get the HPV vaccine.

Follow Christopher Wanjek @wanjek for daily tweets on health and science with a humorous edge. Wanjek is the author of "Food at Work" and "Bad Medicine." His column, Bad Medicine, appears regularly on Live Science.

Christopher Wanjek
Live Science Contributor

Christopher Wanjek is a Live Science contributor and a health and science writer. He is the author of three science books: Spacefarers (2020), Food at Work (2005) and Bad Medicine (2003). His "Food at Work" book and project, concerning workers' health, safety and productivity, was commissioned by the U.N.'s International Labor Organization. For Live Science, Christopher covers public health, nutrition and biology, and he has written extensively for The Washington Post and Sky & Telescope among others, as well as for the NASA Goddard Space Flight Center, where he was a senior writer. Christopher holds a Master of Health degree from Harvard School of Public Health and a degree in journalism from Temple University.