HPV Cancer Resources

If you’re on this page, you’ve likely been diagnosed, or had a loved one diagnosed, with oral, throat, or head and neck cancer. Is there a difference? These terms are rather vague, as there are lots of places in your mouth and throat that can develop cancer, and symptoms (like lumps) sometimes appear on your neck as well. For our purposes we will divide these cancers into two groups: oral cavity cancers (includes the gums, salivary glands, the floor of your mouth, the hard palate at the top of your mouth, and the front two thirds of your tongue) and oropharyngeal cancers (includes your tonsils, the base (back one-third) of your tongue, your soft palate, and the back of your throat). Technically, all of these are “head and neck” cancers, are they are also known as squamous cell carcinomas (SCC) because of the type of cell they arise in.

Historically, squamous cell carcinomas (cancers) of the oral cavity (OCSCC) and oropharynx (OPSCC) were grouped together as essentially the same diseases. The terms “oral” and “oropharyngeal” were both used to describe these cancers. Nowadays the terms “oral” and “oropharyngeal” have very distinct meanings, and they are no longer used interchangeably. This is because clinical research has distinguished one from the other in many respects other than just where they are located in your mouth. These include other risk factors (such as smoking), patient demographics, the actual pathology of the tumor, and how they should be treated.

As you can see in the chart below:
Oral cavity cancers are mostly associated with smoking and/or drinking.

Oropharyngeal cancers come in two types, as indicated below, and are grouped according to whether they are associated with an HPV infection (HPV positive) or no infection (HPV negative).
HPV negative oropharyngeal cancers are, like oral cancers, mostly associated with smoking and drinking.
HPV positive oropharyngeal cancers are actually caused by the viral infection.

Most of the visitors to this website will have HPV+ OPSCC, but the easiest way to describe these cancers is to say that you have HPV positive oropharyngeal cancer.

From WebMD:
Most cancers that involve a tumor are staged in five broad groups. These are usually referred to with Roman numerals. Other kinds, like blood cancers, lymphoma, and brain cancer, have their own staging systems, but they all tell you how advanced the cancer is.

Stage O means there's no cancer, only abnormal cells with the potential to become cancer. This is also called carcinoma in situ.

Stage I means the cancer is small and only in one area. This is also called early-stage cancer.

Stage II and III mean the cancer is larger and has grown into nearby tissues or lymph nodes.

Stage IV means the cancer has spread to other parts of your body. It's also called advanced or metastatic cancer.

Another approach used by doctors to determine your overall cancer stage is the TNM system, short for tumor, node, and metastasis. Your doctor will measure each of these and give it a number or an "X" if a measurement can't be determined. The symbols are a bit different for each type of cancer, but this is generally what they mean:

Tumor (T): "T" followed by a number from 0-4 tells you how large the tumor is and sometimes where it's located. TO means there is no measurable tumor. The higher the number, the bigger the tumor.

Node (N): "N" followed by a number from 0-3 tells you if the cancer has spread to your lymph nodes. These are glands that normally filter things like viruses and bacteria before they can infect other parts of your body. NO means lymph nodes aren't involved. A higher number means the cancer is in more lymph nodes, and farther away from the original tumor.

Metastasis (M): "M" is followed by either 0 or 1. It says if the cancer has spread to organs and tissues in other parts of your body. A 0 means it hasn't, and a 1 means it has.

The staging system for HPV positive oropharyngeal cancers has changed over time as doctors have gotten a clearer understanding of what causes the disease. HPV positive oropharyngeal cancers are actually treated as a separate disease than HPV negative oropharyngeal cancers. There are more details at other locations on this website, but in general (and all cancer cases are different), oropharyngeal cancers caused by HPV are much more treatable, and have a much higher five-year survival rate, than HPV negative cancers.

The table below show you the old and the new staging system. I wouldn’t worry about the details, but if you’re interested ask your doctor to explain it to you. The older staging system listed here is from the 7th edition (2010) of the American Joint Committee on Cancer (AJCC). It was realized over the past few years that this older staging system may not accurately reflect the differences in stage-related prognosis as a resource to guide patient treatment plans. Therefore, the AJCC released the 8th edition of the cancer staging manual, which became effective January 1st 2017. This new staging system contains significant modifications compared to the earlier guidelines, and are influence how your head and neck cancer will be treated. Patients who were diagnosed prior to 2017 will have had their cancers assigned a stage using the old system, those after Jan. 2017 will have been done using the new system.

The two cannot generally be directly compared, that is, the exact same cancer might have gotten a different classification before 2017 than afterwards.

The eighth edition of HPV cancer staging separates oropharyngeal squamous cell carcinomas (OPSCC) into HPV+ and HPV- unrelated OPSCC based on p16INK4a overexpression (p16+), as a surrogate marker for HPV. However, OPSCC is histologically and clinically heterogenous including tonsillar and base of tongue squamous cell carcinomas (TSCC and BOTSCC respectively), and carcinomas of soft palate and walls (otherOPSCC). The significance of HPV is established in TSCC/BOTSCC, while its role in otherOPSCC is unclear, which is not considered in the eighth edition. Here, p16+ was therefore evaluated in relation to overall survival (OS) and tumor stage per OPSCC subsite in a retrospective clinical study.

All 932 patients, treated with curative intent in Stockholm 2000–2016 with OPSCC, previously analyzed for p16 expression, were included. Clinical data, including stage and overall survival, was collected retrospectively. Patients with p16+ other OPSCC had significantly poorer OS compared to patients with p16+ TSCC/BOTSCC (p = 0.005) and their survival was similar to that of patients with p16-otherOPSCC/TSCC/BOTSCC. Moreover, patients with eighth edition stage I-II and p16+ otherOPSCC had a significant poorer overall survival compared to patients with p16+ TSCC/BOTSCC and similar stage (p = 0.02). Lastly, patients with otherOPSCC and low seventh edition staging had a significant better overall survival, as compared to those with a high stage (p = 0.019) while no hazard discrimination was observed with seventh edition TSCC/BOTSCC. Conclusion: Results indicate a risk of misclassification of patients with otherOPSCC and low eighth edition . We suggest that p16 should only be evaluated in TSCC/BOTSCC and that patients with otherOPSCC should all be staged as patients with HPV-unrelated (p16-) OPSCC.

Marklund, L. et al Survival of patients with oropharyngeal squamous cell carcinomas (OPSCC) in relation to TNM 8 – Risk of incorrect downstaging of HPV-mediated non-tonsillar, non-base of tongue carcinomas. European J. of Cancer DOI:https://doi.org/10.1016/j.ejca.2020.08.003.

Cancer staging is what is used to determine what type of treatment each patient may get. Since the treatments for head and neck cancers have significant detrimental effects (referred to as morbidity), doctors don’t want you to get any more treatment than is needed. After all, surgery, chemo, and radiation will have an effect on how you eat, breathe, and look. Determining what treatment to use is difficult. Doctors are always trying to figure out the best way to pick the best treatment without overtreating. Clinical trials are currently under way to use artificial intelligence programs to help determine what the best treatment is. Technically, they are seeking to validate a neural network-based deep learning algorithm based on diagnostic computed tomography (CT) scans, pathology, and clinical data. Early results look promising, and the hope is that the AI program will produce better outcomes for most patients than even the most highly trained doctors. More details can be found here.

Screening for Extranodal Extension with Deep Learning: Evaluation in ECOG-ACRIN E3311, a Randomized De-Escalation Trial for HPV-Associated Oropharyngeal Carcinoma.