HPV-positive oropharyngeal cancer

Human papillomavirus-positive oropharyngeal cancer
Other names	HPV16+ oropharyngeal cancer, HPV16+OPC
Microscope image of tumour showing HPV positivity by in situ hybridization
Specialty	Oncology
Symptoms	Sore or blister in back of mouth, difficulty with speech, swallowing or breathing, swelling in neck, loss of appetite, loss of weight, and weakness
Causes	Human papilloma virus
Risk factors	oral sexual contact
Diagnostic method	Endoscopy, Biopsy, Staining for p16, CT Scan,
Differential diagnosis	Tobacco associated oropharyngeal cancer
Prevention	Vaccination
Treatment	Surgery, radiation, chemotherapy
Frequency	22,000 cases globally (2008)[1][2]

Human papillomavirus-positive oropharyngeal cancer (HPV-positive OPC or HPV+OPC), is a cancer (squamous cell carcinoma) of the throat caused by the human papillomavirus type 16 virus (HPV16). In the past, cancer of the oropharynx (throat) was associated with the use of alcohol or tobacco or both, but the majority of cases are now associated with the HPV virus, acquired by having oral contact with the genitals (oral-genital sex) of a person who has a genital HPV infection. Risk factors include having a large number of sexual partners, a history of oral-genital sex or anal–oral sex, having a female partner with a history of either an abnormal Pap smear or cervical dysplasia, having chronic periodontitis, and, among men, younger age at first intercourse and a history of genital warts. HPV-positive OPC is considered a separate disease from HPV-negative oropharyngeal cancer (also called HPV negative-OPC and HPV-OPC).

HPV-positive OPC presents in one of four ways: as an asymptomatic abnormality in the mouth found by the patient or a health professional such as a dentist; with local symptoms such as pain or infection at the site of the tumor; with difficulties of speech, swallowing, and/or breathing; or as a swelling in the neck if the cancer has spread to local lymph nodes. Detection of a tumour suppressor protein, known as p16, is commonly used to diagnose an HPV associated OPC. The extent of disease is described in the standard cancer staging system, using the AJCC TNM system, based on the T stage (size and extent of tumor), N stage (extent of involvement of regional lymph nodes) and M stage (whether there is spread of the disease outside the region or not), and combined into an overall stage from I–IV. In 2016, a separate staging system was developed for HPV+OPC, distinct from HPV-OPC.

Whereas most head and neck cancers have been declining as smoking rates have declined, HPV-positive OPC has been increasing. Compared to HPV-OPC patients, HPV-positive patients tend to be younger, have a higher socioeconomic status and are less likely to smoke. In addition, they tend to have smaller tumours, but are more likely to have involvement of the cervical lymph nodes. In the United States and other countries, the number of cases of oropharyngeal cancer has been increasing steadily, with the incidence of HPV-positive OPC increasing faster than the decline in HPV-negative OPC. The increase is seen particularly in young men in developed countries, and HPV-positive OPC now accounts for the majority of all OPC cases. Efforts are being made to reduce the incidence of HPV-positive OPC by introducing vaccination that includes HPV types 16 and 18, found in 95% of these cancers, prior to exposure to the virus. Early data suggest a reduction in infection rates.

In the past, the treatment of OPC was radical surgery, with an approach through the neck and splitting of the jaw bone, which resulted in morbidity and poor survival rates. Later, radiotherapy with or without the addition of chemotherapy, provided a less disfiguring alternative, but with comparable poor outcomes. Now, newer minimally invasive surgical techniques through the mouth have improved outcomes; in high risk cases, this surgery is often followed by radiation and/or chemotherapy. In the absence of high quality evidence regarding which treatment provides the best outcomes, management decisions are often based on one or more of the following: technical factors, likely functional loss, and patient preference. The presence of HPV in the tumour is associated with a better response to treatment and a better outcome, independent of the treatment methods used, and a nearly 60% reduced risk of dying from the cancer. Most recurrence occurs locally and within the first year after treatment. The use of tobacco decreases the chances of survival.