There are over 100 strains of the human papillomavirus (HPV), but experts consider only a handful of them to be a risk to human health. These are the strains have been linked with an increased risk of certain cancers such as cervical cancer, vulvar cancer, penile cancer, and anal cancer. However, many of the remaining strains of HPV are commensal viruses, meaning they are common infections that do not usually cause symptoms or disease and are little more than harmless stowaways on our skin.
Prior to 2018, scientists also believed that some strains of HPV may increase the risk of nonmelanoma skin cancers. However, a recent study published by Dr. Anna Nichols, a dermatologist and an assistant professor in the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery at the University of Miami Comprehensive Cancer Center, and Dr. Tim Ioannides, from Treasure Coast Dermatology in Port St. Lucie has provided new evidence showing that HPV is an indication of already compromised immune systems, and injecting SCC patients with the HPV vaccine Gardasil 9 may be an effective treatment for tumors that have otherwise been deemed inoperable.
Squamous cell carcinoma
Squamous cell carcinoma is the second-most common type of skin cancer, with more that 250,000 new SCC diagnoses occurring every year in the United States. Middle-aged and elderly persons are most likely to be affected, and especially those that have naturally fairer complexions and have been exposed to the sun with frequency.
The squamous cells are flat, thin cells in the middle and upper layer of the epidermis, and cancer occurs in them when the cells’ DNA mutates to multiply rapidly and continue growing where they would normally die off. These mutations are most often caused by long-term exposure to ultraviolet (UV) radiation found in sunlight and in commercial tanning lamps and tanning beds.
If treated in a timely manner, SCC is highly treatable and unlikely to spread to other areas of the body, but certain aggressive types can spread to the lymph nodes and other organs. It is most often found on your scalp, the backs of your hands, your ears or your lips, and if left untreated can destroy much of the tissue surrounding the originating location of the tumor, resulting in the loss of a nose or ear.
Dr. Ioannides says of typical treatment: “dermatologists use a variety of different surgical treatment options depending on location of the tumor, size of the tumor, microscopic characteristics of the tumor, health of the patient, and other factors. Most treatment options are relatively minor office-based procedures that require only local anesthesia. Surgical excision to remove the entire cancer is the most commonly used treatment option. Mohs micrographic surgery can also be used to treat this form of cancer.”
Human papillomavirus (HPV) and Gardasil
Human papillomavirus, a DNA virus, is the cause of HPV infection, a viral infection that can be sexually transmitted and infect the genital area or picked up from touching surfaces and infect the skin. With over 170 different varieties, some types of HPV infection cause warts, while others lead to different types of cancer. This doesn’t occur with most HPV infections, but some types have been shown to be linked to cancers of the anus, penis, vagina, vulva, and back of the throat (oropharyngeal). Nearly all people are infected by a strain of HPV at some point in their lives.
In 2006, the vaccine Gardasil was approved by the Food and Drug administration for medical use in the United States to prevent types 6, 11, 16, and 18 of the human papillomaviruses. Types 16 and 18 are considered high-risk HPVs and are responsible for an estimated 70% of cervical cancers, and are also the cause of most HPV-induced penile, anal, vulvar, and vaginal cancer cases. HPV types 6 and 11 cause an estimated 90% of genital warts cases. In 2014 the nine-valent version Gardasil 9 was approved to protect against infection with the strains covered by the first generation as well as five additional strains that account for 10% to 20% of cervical cancers.
HPV and skin cancer studies
Prior studies of the human papillomavirus and squamous cell carcinoma found the virus stimulates the development of the cancer. One study found that mice infected with the type 38 strain of the virus were more likely to develop SCC when they were exposed to UV light than other mice that weren’t infected but were also exposed to UV light. Another reviewed blood sample records in Norway and Sweden and found that people infected with a certain group of HPVs that make their home in skin cells were 30% more likely to develop squamous cell carcinoma over a 30-year period than those not infected with the group of viruses.
Because of these correlations suggesting that HPV infections may play a role in the development of skin cancer, Dr. Nichols initially wanted to see if the HPV vaccine could help prevent skin cancer. Along with her colleagues, she administered three doses of Gardasil 9 to two individuals with healthy immune systems who previously had skin cancer growths removed. After undergoing skin examinations searching for new cancers every three months for up to 16 months after their first dose of the vaccine, both patients developed fewer squamous cell carcinomas and basal cell carcinomas than prior to receiving the vaccine.
Utilizing the HPV vaccine for treatment
Dr. Nichols along with her colleague Dr. Ioannides later tried to use this technique on one of her patients, a 97-year-old woman who had multiple metastatic lesions on her right leg. She had too many tumors to remove them all surgically, and previous topical and injectable therapies had all failed. She was offered the option of systemic chemotherapy, but that came with serious side effects without providing much certainty.
In an effort to treat the tumors while maintaining the patient’s quality of life, they initially administered the vaccine systematically through two intramuscular injections into the woman’s arm. Dr. Nichols noticed a local inflammatory response in the majority of the tumors and upon discussing the results, Dr. Ioannides urged her to try a radical new approach. Noting other vaccines had successfully been injected intratumorally to treat other maladies, he suggested they use Gardasil 9 “off-label” — for a different purpose than previously approved for by the FDA — and use the vaccine as a treatment to rid the patient of the existing tumors.
Taking Dr. Ioannides’ advice, Dr. Nichols injected the vaccine into each of the woman’s three largest tumors twice, and within weeks began to see shrinkage in not only the injected lesions, but additional untreated tumors. She realized that the woman’s immune system was likely having a systematic response to the medicine, so rather than inject each tumor individually she simply injected the largest tumors two more times with increasingly smaller doses, and after a year and four injections total, every tumor had disappeared.
Since the study, the patient has gone on to celebrate her 100th birthday and has not developed any additional tumors. Dr. Nichols received the Skin Cancer Foundation’s $25,000 Ashley Trenner Research Grant Award and is now treating several other patients with the off-label vaccine treatment. She is also putting together a clinical trial, and hopes to find out more about how it works and who it works best for in the near future.
Tim Ioannides MD was awarded a patent for the novel use of the Gardasil 9 vaccine. He was involved in the study as a voluntary faculty member at the University of Miami, but also runs his dermatological practice Treasure Coast Dermatology out of Port St. Lucie, Florida.
Although it is not entirely clear how or why HPV may be linked to skin cancer, the correlation indicates that it may be possible to develop a vaccine preventing skin cancer, just as one has been developed to prevent cervical cancer. Regardless, it is important to remember that the current best way to prevent the development of skin cancer is to limit your exposure to UV light, both by sun avoidance and consistent usage of an SPF sunscreen.
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