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New Treatments for Throat Cancer, Mouth Cancer, and Head and Neck Cancer

Head and neck cancer has an annual incidence of about 40,000 per year. That makes up for about 5% of the incidence of new cancers. Two-thirds of patients will present with locally or regionally advanced disease. So that’s the most common presentation for throat cancer, mouth cancer, head and neck cancer, oral cancer, and tongue cancer. Traditional therapy for these two-thirds has been surgery and/or radiotherapy. This means surgery with postoperative radiation or radiation alone if patients were unresectable or inoperable. When they receive this kind of treatment most recurred within a two year period of time. Some patients developed distant metastases but most recurred locally or regional.

If you look at the five year survival term - for all cancers together. So these are now the two-thirds advanced and the one-third early stage that survival rates usually are 30% or less. But what this slide shows you is that there are some differences according to specific anatomic site. That doesn’t necessarily mean that those cancers behave differently from one site to another. So they are all usually squamous cell carcinomas and they all usually are poor prognosis. But it does mean that larynx cancer, shown here, is usually earlier detected and the reason for that is that of all these sites it is the one that has an early warning sign, which is hoarseness.

Anatomically speaking, this is what it’s about. There are some large groups that we put together. The oral cavity, which is usually about 20% of head and neck tumors; these are easily detected and a good physical examination should involve the oral cavity, can be done. Then there is the oropharynx behind it and that is grouped to include the tonsils. That then includes the pharynx as a whole, the nasopharynx - that’s straight back from the nose here.

For the common squamous cell carcinomas, these are the risk factors. And really after the first two, from an epidemiological point of view, it all stops. Tobacco is the most prevalent of these and alcohol use is synergistically a carcinogenic factor with tobacco. And why that is, we don’t understand. It may be that certain carcinogens are dissolved and then pool as they are dissolved in a necrophilic substance such as alcohol. It could also be that at the cellular level there is a synergistic interaction. Most others here are not major on an epidemiological basis.

Before we do that, let’s go into signs and symptoms. We mentioned that these are usually vague and nonspecific. In early stage it is very much hoarseness only for the larynx that can use it. So be suspicious. Do we have good screening for head and neck cancer? No. All you can do is examine the patient. There is no cytological examination or other ways to screen patients. The remainders of the signs and symptoms are really very much related to the specific anatomy. So for the nasopharynx, what you would get - we mentioned that it sits right behind the nose - so you get nasal obstruction, you can get a nosebleed and because the eustachian tube is blocked you can get otitis media. Now once you have cranial neuropathies, and that means it has somehow invaded the skull base, and so it is no longer a very early symptom, and of course posterior cervical lymph nodes.

So this summarizes it up a little and I think that good surveillance and a critical appreciation that this is what can happen to patients if they are smokers and drinkers.

Now there is an entity called lymphadenopathy of unknown primary. So if someone has a mass in the neck, the ENT doctor looks, doesn’t find the primary, and the way to proceed for that these days is to do a fine-needle aspiration of the lymph node and get cytologic diagnosis. It could be lymphoma, and depending on the risk factors, is maybe more likely to be squamous cell carcinoma. You then follow that with a panendoscopy and if the panendoscopy.

Now just a brief example for staging. It’s the usual TNM classification and out of this you have a T that usually goes according to size. This is an example of the oral cavity from T1 to T3, and then T4 meaning invasion of adjacent structures. As a principle that holds up for all head and neck cancer sites. So in this case, what are the adjacent structures? It’s the bone, deep muscle of the tongue - so a fixed tongue - maxillary sinus or skin. The lymph node classification is uniform for all head and neck sites with the exception of nasopharynx cancer, which has its own. So this is what’s typical. It goes from N0 to N3, and N1 is a single ipsilateral lymph node.

Here’s the work-up. Inspection usually with a gloved exam. You can palpate the head and neck area and the oral cavity, neck palpation and from there you move to the more specialty areas; indirect laryngoscopy - that’s with a mirror - you can also now do fiberoptic nasopharyngoscopies. These tell you the local disease. These may sometimes be necessary under anesthesia to also get biopsies. CT or MRI is what should be done, and then you have the definitive endoscopic evaluation where you do a direct laryngoscopy fiberoptically. Now very frequently these patients are at risk for second tumors.

Then finally here, as a clinician, what you want to think about is that we have multiple goals in treating these patients. So we mentioned that local and regional failure is the most common; traditionally about 50-70% of patients. So that is where our therapies are directed, surgery and radiation therapy. You could easily postulate that should locoregional failure ever improve - and there is no evidence for this - that distant failure rates would increase because there is - and we know this from autopsy series - distant micro-dissemination.

So what about the background then? What do we know about multi-step carcinogenesis for head and neck cancer? You’ll hear about this kind of thinking for many of the current solid tumors. It’s of course best established based on Bert Fogelstein’s work in colorectal cancer. In head and neck cancer we don’t have a true sequence of events. So we cannot correlate abnormality A with a specific stage. But we do know that a variety of events happen quite regularly and they include non-random chromosome deletions and rearrangements.

What about HPV? I mentioned this earlier as an area where knowledge is emerging. This has now been looked at a bit more closely and the group at Hopkins has followed up on this but we’ve done this years ago, and others have. Here they took a larger pool of patients, 248 tumor specimens. They were examined for HPV genomic sequences by PCR and overall 62 of these cases were positive for HPV. It was HPV 16 - that’s the one that’s associated with cervical cancer as well - in 56 cases. Now there was a bit of variation according to site and the common ones were oral cavity, 12 of 78, and particularly the oropharynx, the tonsil.

So this is the clinical correlate of multi-step carcinogenesis, and it’s not a very firm one. So in the colorectal area you can have a polyp that becomes larger or multiple and eventually invasive cancer. There is an entity in the head and neck called leukoplakia, a white patch that cannot be removed, and this is taken from Art Scarens book because none of us see it frequently. So this is postulated to be what leads into head and neck cancer, a white patch that cannot be removed. If you biopsy it, it is frequently either dysplasia or hyperplasia.