HPV-Positive Oropharyngeal Cancer: What Patients Need to Know

Oropharyngeal cancer — cancer arising in the tonsils, base of tongue, soft palate, or posterior pharyngeal wall — has changed dramatically over the past two decades. While this type of cancer was historically linked to tobacco and alcohol use, the majority of oropharyngeal cancers diagnosed today are caused by the human papillomavirus, or HPV. If you or a loved one has been diagnosed with HPV-positive oropharyngeal cancer, there are important things you should understand about this disease — including that it generally carries a significantly better prognosis than its HPV-negative counterpart.

What Is HPV, and How Does It Cause Throat Cancer?

Human papillomavirus is an extremely common virus, with most sexually active adults exposed to it at some point in their lives. There are over 200 types of HPV, and most cause no problems at all. However, a small number of high-risk strains — most notably HPV type 16 — can persist in the tissues of the throat and, over years or decades, lead to the development of cancer. This is the same family of viruses responsible for cervical cancer in women.

The important thing to understand is that HPV-related oropharyngeal cancer is not a reflection of lifestyle choices in the same way tobacco-related cancers are. It affects a broad population, and the typical patient is often a middle-aged, otherwise healthy individual — frequently a man in his 50s or 60s — without a significant history of smoking or drinking.

How Is HPV-Positive Oropharyngeal Cancer Different?

HPV-positive oropharyngeal cancer behaves differently from HPV-negative disease in several important ways.

First, and most importantly, outcomes are substantially better. Based on recent research, including a large meta-analysis of over 16,000 patients treated with transoral robotic surgery (TORS), five-year overall survival for HPV-positive oropharyngeal cancer is approximately 90%, compared to about 73% for HPV-negative disease. A large study from Memorial Sloan Kettering Cancer Center of over 1,200 patients found that those who remained disease-free at two years after treatment had survival rates essentially equivalent to the general population. These are genuinely encouraging numbers.

Second, HPV-positive cancers tend to present differently. Patients often notice a painless neck mass — an enlarged lymph node — as their first symptom, sometimes before they have any throat pain or difficulty swallowing. The primary tumor in the tonsil or base of tongue may be small, yet the cancer may have already spread to one or more lymph nodes. Despite this, the prognosis remains favorable.

Third, because outcomes are so much better, the staging system itself was revised. The 8th Edition of the AJCC Cancer Staging Manual, in use since 2018, created a separate staging classification for HPV-positive oropharyngeal cancer. Under the old system, a patient with a small tonsil cancer and several involved lymph nodes might have been classified as Stage IV — which sounds alarming. Under the current HPV-specific staging, the same patient is more appropriately classified as Stage I or II, reflecting the actual expected outcome.

How Is HPV Status Determined?

When a biopsy is taken from the tumor, the pathologist tests for HPV using a marker called p16, which is a protein that is overexpressed in HPV-driven cancers. A strongly positive p16 stain on immunohistochemistry is the standard method for identifying HPV-positive oropharyngeal cancer. In some cases, additional HPV-specific testing (such as HPV DNA in situ hybridization) may be performed for confirmation.

This p16/HPV result is one of the most important pieces of information in your pathology report. If you have been diagnosed with oropharyngeal cancer, make sure you know your HPV status — it fundamentally shapes your treatment plan and expected outcome.

Treatment Options

Treatment for HPV-positive oropharyngeal cancer typically involves one of two primary approaches:

Surgery followed by possible radiation: Transoral robotic surgery (TORS) allows the tumor to be removed through the mouth without external incisions to the jaw or throat. This is combined with a neck dissection to remove lymph nodes. The pathology results from surgery then determine whether additional treatment with radiation (and sometimes chemotherapy) is needed afterward. In favorable cases, surgery alone may be sufficient, or a reduced dose of radiation may be recommended. This is the approach I most commonly employ for eligible patients at our program at St. Luke's Medical Center.

Radiation with concurrent chemotherapy: For patients who are not ideal candidates for surgery, or who have larger tumors, definitive radiation therapy delivered over six to seven weeks with concurrent chemotherapy (typically cisplatin) is an effective alternative with excellent cure rates.

Both approaches are effective, and the choice between them depends on the size and location of the tumor, the extent of lymph node involvement, and patient factors and preferences. This is exactly the kind of decision that is made collaboratively through our multidisciplinary tumor board conference, where surgeons, radiation oncologists, and medical oncologists review each case together.

De-Escalation: Can We Treat With Less?

Because outcomes for HPV-positive oropharyngeal cancer are so favorable with current treatment, there is an active and important area of clinical research focused on de-escalation — the question of whether we can reduce the intensity of treatment to decrease long-term side effects while maintaining the same excellent cure rates.

Side effects from standard full-dose radiation to the throat can be significant and lasting: difficulty swallowing, dry mouth, changes in taste, and stiffness of the jaw. If we can safely use lower doses of radiation, or avoid radiation entirely in selected patients after successful surgery, the long-term quality of life benefits would be meaningful.

Recent long-term data from clinical trials supports the idea that reduced-dose radiation following surgery or induction chemotherapy can produce durable disease control in selected patients. However, de-escalation is not yet the standard of care for all patients, and careful patient selection is essential. Ongoing clinical trials continue to refine which patients can safely receive less treatment.

What About the HPV Vaccine?

The HPV vaccine (Gardasil 9) is highly effective at preventing HPV infection and is recommended for boys and girls starting at age 11-12, with catch-up vaccination available through age 26 (and in some cases up to 45). Because HPV-related oropharyngeal cancer can take 20 to 30 years to develop after initial infection, we expect to see the impact of widespread vaccination on oropharyngeal cancer rates in the coming decades. The vaccine is a true cancer prevention tool.

For patients already diagnosed with HPV-positive oropharyngeal cancer, the vaccine does not play a treatment role, but it may be discussed in the context of preventing future HPV-related conditions.

What Should You Do If You've Been Diagnosed?

If you have been told you have a cancer of the tonsil, base of tongue, or throat, the most important first steps are:

Ensure your pathology has been tested for p16/HPV status. This is essential for accurate staging and treatment planning.

Seek evaluation by a head and neck surgeon experienced in TORS and free flap reconstruction, as well as a multidisciplinary cancer team. The treatment plan for oropharyngeal cancer requires coordination between surgery, radiation oncology, and medical oncology.

Ask about your specific stage and prognosis. For HPV-positive disease, the outlook is generally very favorable, and understanding this can provide meaningful reassurance during a frightening time.

If you have been diagnosed with oropharyngeal cancer, or have a concerning symptom such as a persistent neck mass, sore throat, or difficulty swallowing, I am happy to see you for a consultation. We can be reached at 414-649-3920.

Dr. Steven Sperry is a fellowship-trained head and neck surgeon specializing in head and neck cancer surgery and microvascular free flap reconstruction at Aurora St. Luke's Medical Center in Milwaukee, Wisconsin.