The US Food and Drug Administration (FDA) has expanded the indication for the Gardasil-9 (Merck) vaccine to include prevention of oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58.
This new indication is approved under the FDA’s accelerated approval program and is based on the vaccine’s effectiveness in preventing HPV-related anogenital disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial, which is currently underway.
“At Merck, working to help prevent certain HPV-related cancers has been a priority for more than two decades,” said Alain Luxembourg, MD, director, clinical research, Merck Research Laboratories, in a statement. “Today’s approval for the prevention of HPV-related oropharyngeal and other head and neck cancers represents an important step in Merck’s mission to help reduce the number of men and women affected by certain HPV-related cancers.”
This new indication doesn’t affect the current recommendations that are already in place. In 2018, a supplemental application for Gardasil 9 was approved to include women and men aged 27 through 45 years for preventing a variety of cancers including cervical, vulvar, vaginal, and anal cancer as well as genital warts. But cancers of the head and neck were not included.
The original Gardasil vaccine came on the market in 2006, with an indication to prevent certain cancers and diseases caused by HPV types 6, 11, 16, and 18. It is no longer distributed in the United States.
In 2014, the FDA approved Gardasil 9, which extends the vaccine coverage for the initial four HPV types as five additional types (31, 33, 45, 52, and 58), and its initial indication was for use in both men and women between the ages of 9 through 26 years.
Head and Neck Cancers Surpass Cervical Cancer
More than 2 decades ago, researchers first found a connection between HPV and a subset of head-and-neck cancers (Curr Opin Oncol. 1999;11(3):191-199). The cancers associated with HPV also appeared to have a different biology and disease pattern, as well as a better prognosis, compared with those that were unrelated. HPV is now responsible for the majority of oropharyngeal squamous cell cancers diagnosed in the United States.
These findings provided evidence that HPV vaccination was associated with a reduced frequency of HPV infection in the oral cavity, suggesting that vaccination could decrease the future risk of HPV-associated head and neck cancers.
The omission of head and neck cancers from the initial list of indications for the vaccine is notable because, according to data from the Centers for Disease Control and Prevention (CDC), oropharyngeal cancers are now the most common malignancy caused by HPV, surpassing cervical cancer.
Who Will Benefit?
An estimated 14 million new HPV infections occur every year in the United States, according to the CDC, and about 80% of individuals who are sexually active have been exposed at some point during their lifetime. In most people, however, the virus will clear on its own without causing any illness or symptoms.
Sandra Adamson Fryhofer, MD, MACP, FRCP, helped clarify the adult population most likely to benefit from the vaccine. She pointed out that the HPV vaccine doesn’t treat HPV-related disease or help clear infections, and there are currently no clinical antibody tests or titers that can predict immunity.
“Many adults aged 27-45 have already been exposed to HPV early in life,” she said. Those in a long-term mutually monogamous relationship are not likely to get a new HPV infection. Those with multiple prior sex partners are more likely to have already been exposed to vaccine serotypes. For them, the vaccine will be less effective.”
Fryhofer added that individuals who are now at risk for exposure to a new HPV infection from a new sex partner are the ones most likely to benefit from HPV vaccination.
Confirmation Needed
The FDA’s accelerated approval is contingent on confirmatory data, and Merck opened a clinical trial this past February to evaluate the efficacy, immunogenicity, and safety of the 9-valent HPV vaccine in men 20 to 45 years of age. The phase 3 multicenter randomized trial will have an estimated enrollment of 6000 men.