Head and Neck Cancer Treatment by Stage

"Head and neck cancer" is an umbrella, not a diagnosis. NCI does not write one treatment summary for it. It writes several.

There are separate summaries for the oropharynx and the larynx. Others cover the hypopharynx, the lip and oral cavity, the nasopharynx, the salivary glands and the paranasal sinuses. Each has its own staging. Each has its own surgery and its own evidence.

The site decides what is at risk. A laryngeal tumor puts the voice on the table. An oral cavity tumor puts chewing and the jaw on the table. An oropharyngeal tumor puts swallowing on the table.

So the first question is not the stage. It is where exactly the tumor started.

One thing to hold in mind while reading on: almost all the trial evidence quoted below comes from NCI's oropharyngeal summary, because that is where most of the recent randomized work has been done. It says little about larynx, hypopharynx, nasopharynx, salivary gland or sinonasal cancers, which follow their own pathways. p16 testing, in particular, carries its meaning in the oropharynx and does not transfer to the other sites.

This is the biggest change in the field, and it is a staging change, not just a prognosis note.

NCI records the change. The American Joint Committee on Cancer 8th edition separates oropharyngeal staging by HPV status. One system covers HPV-mediated, p16-positive cancer. Another covers p16-negative cancers of the oropharynx and hypopharynx.

The same stage number means different things in the two systems. A number quoted without the p16 result is not enough information.

How common is it? NCI cites a prospective study of 253 patients. All had newly diagnosed or recurrent head and neck squamous cell carcinoma. HPV was found in 25%. Poor tumor grade raised the chance of finding it. So did an oropharyngeal site.

For early-stage oropharyngeal cancer, NCI states that single-modality treatment is preferred.

Historically that meant radiation alone. That is changing. NCI notes wider use of transoral surgery, including the robotic version. Non-randomized comparisons put quality of life higher with the minimally invasive surgery than with primary radiation.

Non-randomized is the operative word. It means the comparison was not a coin toss, so patient selection could explain part of the difference.

The point stands anyway. In early disease, adding a second treatment adds toxicity without a clear gain, so the aim is to pick one and do it well.

Once the disease is locally advanced, combinations take over: surgery, radiation, chemotherapy, and postoperative treatment for high-risk features.

Two dosing findings are worth knowing.

The first is the cisplatin schedule after surgery. A phase II/III trial compared two doses given with radiation. One arm had a smaller dose weekly. The other had a larger dose every 3 weeks. Both are worked out from body size and given in the treatment unit. In all, 261 patients were enrolled. At 2.2 years of median follow-up, weekly cisplatin was noninferior for overall survival. The hazard ratio was 0.69.

The second concerns cetuximab. Adding weekly cetuximab to curative-intent radiation was compared with radiation alone in 424 patients, and it improved progression-free survival at 54 months of follow-up.

Because HPV-positive oropharyngeal cancer has a better outlook, there was a reasonable idea: swap cisplatin for the gentler cetuximab and keep the cure rate.

RTOG-1016 tested it. Patients had centrally confirmed p16-positive oropharyngeal cancer. They were randomized to radiation with cetuximab, or radiation with cisplatin. Of 987 enrolled, 849 were randomized. Radiation was given on an accelerated schedule over six weeks; the dose and fractionation for any individual are planned by a radiation oncologist.

At 4.5 years of median follow-up, cetuximab missed the noninferiority criteria for overall survival. Estimated 5-year overall survival was 77.9% with cetuximab. With cisplatin it was 84.6%. Progression-free survival was significantly worse on cetuximab. So was locoregional failure.

Acute moderate to severe toxicity was similar in both arms, at 77.4% and 81.7%.

That is a de-escalation attempt that failed on its own terms. NCI notes that other reduced-dose radiation studies are still ongoing.

Some of the most consequential decisions here concern function and are made before treatment starts.

Teeth come first. NCI's oral cavity summary says dental status evaluation should be performed before therapy, to prevent late consequences. It also says patients should be counseled to stop smoking before radiation begins.

Late toxicity data show what is being prevented. In one reported oropharyngeal series, late toxicities of grade 2 or higher were salivary 67%, mucosal 24%, esophageal 19%, skin 12% and osteoradionecrosis 6%. Dry mouth of grade 2 or higher affected 55% at 6 months. That fell to 25% at 12 months, and 16% at 24 months.

For laryngeal cancer, NCI is specific about who should be in the room. Intermediate lesions should be discussed in multidisciplinary consultation before therapy is prescribed. It names surgery, radiation therapy, and dental and oral surgery.

Two long-term items belong on the list.

The first is the thyroid. Radiation to the neck causes hypothyroidism in 30% to 40% of people who receive external-beam treatment. That is a blood test, not a symptom to wait for.

The second is a new cancer rather than the old one. Second primary tumors of the aerodigestive tract have been reported in as many as 25% of patients whose first lesion was controlled.

One more thing sits upstream of staging entirely.

NCI's oral cavity summary names three precancerous lesions: leukoplakia, erythroplakia and mixed erythroleukoplakia. Leukoplakia is the most common. The World Health Organization defines it as a white patch or plaque that cannot be classified as any other disease.

That definition is one of exclusion. Candidiasis, lichen planus and leukoedema have to be ruled out first.

Erythroplakia is less common. It is also much more likely to be linked with dysplasia or carcinoma. NCI adds that leukoplakia is becoming less common in the United States, as tobacco use falls.

For the disease overall, see head and neck cancer. For the day-to-day effects of treatment, see mouth and throat problems. For what a PD-L1 score means, see what does PD-L1 CPS mean.

Treatment here sits next to the airway and the swallowing muscles, so a few problems cannot wait for the next clinic slot.

• Call 911 or go to an emergency department if you have severe difficulty breathing, meaning you are gasping, choking, or cannot get words out. The NHS puts breathing trouble of that kind in the emergency group for laryngeal cancer. Do the same for heavy bleeding from the mouth, throat or a neck wound that does not stop with pressure, and for a temperature of 100.4°F (38°C) or higher while you are receiving chemotherapy or chemoradiation. CDC calls fever during chemotherapy a medical emergency; radiation on its own does not usually drop your counts that way. Do not take anything to bring the temperature down first, because a fever reducer can mask what is happening.
• Call your care team the same day if pain in your mouth, lips or throat is making it hard to eat, drink or sleep, which is the line NCI draws for mouth and throat problems, or if you have stopped being able to keep fluids down.
• Call your care team within a day or two if you notice new shortness of breath that is milder than the emergency picture above, a new or growing lump in the neck, white patches or sores in the mouth, or a jaw that will not open as far as it used to. Late problems after neck radiation include a new second tumor, so a new lump is worth reporting even years on.

• NCI PDQ — Oropharyngeal Cancer Treatment (Health Professional Version)
• NCI PDQ — Laryngeal Cancer Treatment (Health Professional Version)
• NCI PDQ — Lip and Oral Cavity Cancer Treatment (Health Professional Version)
• NCI — Mouth and Throat Problems during Cancer Treatment
• NCI — Infection and Neutropenia during Cancer Treatment
• CDC — Watch out for fever during cancer treatment
• NHS — Laryngeal cancer: symptoms