August 2023 | George M. Pikler, M.D., Ph.D., FACP

Human Papillomavirus [HPV] and Cancer

Infection with human papillomaviruses (HPVs) is a driver of several neoplasms, especially cervical, anogenital, and oropharyngeal squamous cell cancers. Even esophageal adenocarcinoma (EAC) is attributed to the human papillomaviruses (HPVs). Recently, HPV has also been found to be present and active in lung cancer and may also contribute to skin cancers. HPVs are double-stranded circular DNA viruses sexually transmitted via genital contact but can also be passed on by skin and mouth contact.

Epidemiological studies show that several HPV types are carcinogenic. Among them, two high-risk strains, HPV16 and HPV18, are the most prevalent and the major cause of HPV-associated cancers. They cause 70-80 per cent of cervical cancers in women and up to 90 per cent of HPV-related cancers in men.

The Centers for Disease Control and Prevention estimates that approximately 42,700 new cases of HPV-associated cancers occur in the United States each year. Over the past decade, oropharyngeal squamous cell carcinoma (OPSCC) has become the most prevalent HPV-associated cancer in the United States, and the incidence is rapidly increasing year by year. Patients with HPV-associated OPSCC have a significant better prognosis and treatment outcomes than those with HPV-negative OPSCC. Despite generally favorable outcomes,15% to 25% of patients with HPV-OPSCC will have a recurrence.

Circulating tumor HPV DNA (ctHPVDNA) has emerged as a promising biomarker for HPV-associated OPSCC, because approximately 90% of patients have detectable plasma ctHPVDNA at the time of diagnosis and the first indication of post treatment occult recurrence, (1) predating identification by routine clinical and imaging studies. A blood test (liquid biopsy) to detect circulating tumor tissue modified viral (TTMV)-HPV DNA is currently commercially available. The test should be obtained at least seven days after a biopsy confirms the diagnosis, and prior to initiating treatment. During and after treatment, serial monitoring using this test is also recommended to determine the response to treatments and detect occult recurrences. Although preventive vaccines can protect from HPV infections, including those caused by HPV-16 and HPV-18, there are still many new cases of HPV-related cancers worldwide. HPV vaccines work best when given to someone who has never been exposed to the virus. Emerging evidence suggests that they are effective after just one dose—rather than the two or three that are currently recommended in most countries.

(1) Clin Cancer Res (2022) 28 (19): 4292–4301.

Erica Cross, PA


Erica is a board certified Physician Assistant. She obtained her Master’s degree in Physician Assistant studies from Our Lady of the Lake College in Baton Rouge, LA. She began practicing in 2011 and has worked clinically in Orthopedics and Dermatology. The majority of her career has been spent in a Dermatology practice where she assisted in Mohs surgery, treating various types of skin cancer. She also teaches in the medical simulation department at the University of South Alabama and enjoys every aspect of medical education.