HPV Cancer Resources

HPV-caused cancers are generally treated in the same way as other cancers are treated. Here are the methods used:

Surgery. Whether or not this is an option depends on a number of factors. It’s an option for all of the organs affected by HPV-caused cancers. In addition to regular surgery, some head and neck cancer patients with small oral tumors will be offered TORS - Trans Oral Robotic Surgery. A surgeon guides a surgical robot to remove the tumor by going in through the mouth. This procedure is much less invasive than the procedure it replaced, which often severely affected patients with head and neck cancers. Another possible option is transoral laser microsurgery ELS - Endoscopic Laser Surgery, which is also generally restricted to early stage cancers, especially those found in the larynx. With laser surgery the cancer is either vaporized with the laser, or cut out. Both of these surgical techniques are often connected to a neck dissection procedure, where the surgeon removes lymph nodes in the neck and a pathologist examines them for signs of cancer to see if the tumor has spread there. TORS can also be used to successfully remove HPV negative head and neck cancers. Both TORS can trans oral laser microsurgery can lead to successful removal of the tumor. The primary measure of success is whether or not the patient remains cancer free. There are also secondary measures that can be made. For example, one study showed that patients getting trans laser microsurgery have a lower rate of needing nasogastric feeding tubes one month after surgery.

Note: a new second-generation surgical robot has been developed for TORS. It’s known as a single port system because all of the surgical tools enter the mouth through a single port, in contrast to the multiple ports found in the current DaVinci surgical robot. This has some significant practical advantages, which you can read about here.

Another option is a combination of immunotherapy treatment followed by robotic surgery. The idea is to use the immunotherapy to shrink the size of the tumor to one that can then be successfully removed by TORS. You can read more about this clinical trials approach here.

Below is a look at the general standard of treatment, which is combination chemotherapy and radiation. After reading this section, you may want to look below for the section Dose De-escalation Therapy for HPV+ Oral Cancers

Chemotherapy. These are drugs that non-specifically attack dividing cells, which includes those in the tumor as well as other tissues in your body (e.g. hair follicles, intestinal linking, blood cell development). Many factors are involved in choosing a chemotherapy regimen; details can be found here. Some chemotherapy drugs are designed to be used concurrently with radiation treatment, which increases the effectiveness of both agents. One example of this is cisplatin and radiation therapy for treating head and neck cancers.

Radiation. This is often used, especially in head and neck cancers. There are actually two types of radiation approaches used:

External beam therapy (EBT): a method for delivering a beam of high-energy x-rays to the location of the tumor. It is sometimes referred to as photon therapy. Some patients, and in areas where it is available, will be offered proton beam therapy, a different type of radiation. The idea behind proton beam therapy is that there will be less damage to the surrounding tissues, resulting in faster and/or better recovery, with less damage to the surrounding tissue. Whether or not this is truly advantageous in terms of overall better patient outcomes (e.g. improved survival) has not yet been determined. You can read about it’s advantages and disadvantages here. Note: many insurance plans do not cover proton beam therapy, considering it still to be experimental. Proton beam therapy is significantly more expensive than standard X-ray (i.e. external beam) therapy because the machines are much larger and more expensive to build and run.

Here are a couple of studies you can review with your doctor if you are considering proton beam therapy.
References: Baumman, B.C. et al Comparative Effectiveness of Proton vs Photon Therapy as Part of Concurrent Chemoradiotherapy for Locally Advanced Cancer. JAMA Oncol. 2020;6(2):237-246. doi:10.1001/jamaoncol.2019.4889 FREE download.

Also look at Frank, S.J. et al Comparing Intensity-Modulated Proton Therapy With Intensity-Modulated Photon Therapy for Oropharyngeal Cancer: The Journey From Clinical Trial Concept to Activation. Seminars in Radiation Oncology Volume 28, Issue 2, April 2018, Pages 108-113. FREE download.

The radiation beam is generated outside the patient (usually by a linear accelerator for photon/x-ray and a cyclotron or synchrotron for proton beam) and is targeted at the tumor site. These radiation beams can destroy the cancer cells, and conformal treatment plans allow the surrounding normal tissues to be spared.

Another option is intensity-modulated radiation therapy (IMRT): an advanced mode of high-precision radiotherapy that utilizes computer-controlled x-ray accelerators to deliver precise radiation doses to a malignant tumor or specific areas within the tumor. The radiation dose is designed to conform to the three-dimensional (3-D) shape of the tumor by modulating—or controlling—the intensity of the radiation beam to focus a higher radiation dose to the tumor while minimizing radiation exposure to healthy cells.

Another potentially important development is something known as an MRI-Linac, or an MRI linear accelerator. This is not a new type of radiation machine. It’s an upgrade to the linear accelerator, a longtime workhorse of cancer care that hits a patient’s tumors with radiation. The MRI-Linac merges that machine with its other namesake, a magnetic resonance imaging scanner, or MRI. The result is a machine that aims to treat cancer far more precisely than the tools widely used for years. It’s meant to image the tumor better in real time. That’s especially important when hitting a tumor with radiation. Everything inside the body is constantly on the move — organs, tissues, and even tumors. A tumor can shift an inch with just a deep breath. That’s made radiation therapy — which beams high-energy rays at a tumor — a challenging business. The MRI-Linac is designed to tamp down on those toxic effects by giving providers a way to watch where radiation is hitting in real time and make modifications. The MRI-Linac has a screen that shows patients their tumor and the radiation area. It looks like two circles of a Venn diagram, one the tumor and one the radiation. Providers have the patient hold their breath until the tumor almost completely overlaps with the radiation area. When they need to take a breath, the tumor might move out of that radiation area — and the machine automatically knows to pause the radiation until the tumor is in the right spot again.

TomoTherapy is a combination of intensity-modulated radiation therapy using a linear accelerator combined with 3D imaging from computerized tomography (CT scanning). The idea is to use highly targeted radiation beams to deliver radiation with extreme precision to treat the cancer while hopefully minimizing the damage to surrounding healthy tissues. More technically, it combines intensity-modulated radiation therapy (IMRT) with the real-time accuracy of CT scanning (also known as image-guided radiation therapy, or IGRT).

UPDATE:
The American Society for Radiation Oncology (ASTRO) issued new guidelines in 2024 concerning radiation treatment for treatment of HPV-caused oropharyngeal cancer. Details can be found in this article: Margalit, D.N. et al Radiation Therapy for HPV-Positive Oropharyngeal Squamous Cell Carcinoma: An ASTRO Clinical Practice Guideline. DOI:https://doi.org/10.1016/j.prro.2024.05.007

Summary from the Dana-Farber Cancer Center: "The expert task force recommends optimal dosing regimens for radiation therapy when used alone or after surgery, incorporating the latest data on minimizing doses to areas that may affect patient quality of life such as swallowing. Concurrent cisplatin chemotherapy is recommended for more advanced tumors or multiple lymph nodes. For patients ineligible for cisplatin, a shared decision-making approach is emphasized and concurrent cetuximab, carboplatin/5-fluorouracil, or taxane-based systemic therapy are conditionally recommended. Recommendations are also given for post-treatment assessment of response to therapy."

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Immunotherapy. This is a technique that harnesses the body’s immune system to attack the tumor. It’s a relatively new technique, and is the subject of intense study and numerous clinical trials. There are currently two immunotherapy drugs approved for treating head and neck cancers, pembrolizumab (Keytruda®) and nivolumab (Opdivo®). Both belong to a class of drugs known as checkpoint inhibitors. You can learn about how they work here. Merck first clinched an accelerated approval to use Keytruda in recurrent or metastatic cases in 2016, targeting patients whose disease progressed on or after platinum-based chemotherapy. On June 11, 2019, the FDA converted it into a full approval right at the end of a priority review period, and additionally stamped its OK on Keytruda as a frontline treatment for head and neck cancer. That covers both monotherapy (in patients whose tumor express PD-L1) and a combination with platinum and fluorouracil, or FU (whole population). In the Phase III KEYNOTE-048 clinical trial, Keytruda improved overall survival over the standard regimen comprising cetuximab and carboplatin or cisplatin plus FU. The hazard ratio was 0.78 (p=0.0171) for PD-L1 positive patients in the monotherapy group and 0.77 (p=0.0067) for the entire combo cohort. “Head and neck squamous cell carcinoma has historically presented many challenges to physicians and patients, including limited treatment options and physical and functional issues caused by the disease and its treatment,” said Jonathan Cheng, Merck’s VP of clinical research.

Immunotherapy, thought promising, also has a number of unusual side effects that can crop up. Check out this article New Drugs, New Side Effects: Complications of Cancer Immunotherapy from the National Cancer Institute that discusses some of these problems, and why they are difficult to predict.

Precision medicine. In this approach, some type of agent (generally a small drug or an antibody) is directed at a protein that is important to the growth of the tumor. These types of drugs are used to treat a number of different types of cancer because they target key proteins that are involved in making cells cancerous across a wide range of tissues. One example of this is larotrectinib (brand name: Vitrakvi), a drug that targets specific genetic change in NTRK genes. This type of genetic change is uncommon, but does occur in a range of cancers, including head and neck cancer. Larotrectinib is approved as a treatment for head and neck cancer that is metastatic or cannot be removed with surgery and has worsened with other treatments. In the case of HPV-caused cancers, scientists are working to develop drugs that target two viral proteins, E6 and E7, that are believed to be critically important to the process by which normal cells are transformed into cancer cells. There are currently no precision medicine drugs on the market directly targeted against HPV-caused tumors, although there are some in clinical trials.

I’m generally not a big fan of looking at survival rates for various cancers, because the numbers are simply averages, and you may do better or worse than the average. How you do with your treatments will depend a lot on what stage your cancer was at when it was found, how effective the treatments are, and how well you tolerate these treatments. There is a lot of inter-individual variability, and patients diagnosed with the same cancer type and staging can and do have very different outcomes. Some patients may be eligible to participate in a clinical trial, in which a new drug or treatment is tested. In addition, advances in the treatment of many cancers have been seen in recent years, rendering these survival numbers out of date and not relevant. If you must see this info, here’s a recent summary:
Five-year relative survival for human papillomavirus-associated cancer sites (2018) Rezzaghi et al Cancer 2018;124:203-211

There are a number of potential side effects that cancer patients can experience as a part of their radiation therapy. These can be both general and specific (vary due to the various locations irradiated).

Common side effects of radiation therapy include:

Skin problems. Some people will experience dryness, itching, blistering, or peeling. Skin problems usually go away a few weeks after treatment ends. If skin damage becomes a serious problem, your doctor may change your treatment plan.

Fatigue. Feeling tired or exhausted almost all the time. Your level of fatigue often depends on your treatment plan. For example, radiation therapy combined with chemotherapy may result in more fatigue.

Long-term side effects. Most side effects go away after treatment. But some continue, come back, or develop later. These are called late effects. One example is the development of a second cancer. This is a new type of cancer that develops because of the original cancer treatment. The risk of this late effect is low. And the risk is often smaller than the benefit of treating the primary, existing cancer.

Here’s a list of some of the specific problems you might encounter, organized by the treatment areas:

Head and neck

Dry mouth (also known as xerostomia) is caused by a reduction in the flow of saliva. Details on how this arises, and what you can do to combat it, can be found here. I also came across this analysis of whether or not acupuncture can provide some measure of relief from xerostomia (dry mouth), a lack of saliva production often seen in H&N cancer patients who have been treated with radiation. A critical look at the data in this study indicates that, unfortunately, acupuncture is NOT helpful in treating this. FYI. Here's the reference: https://respectfulinsolence.com/2019/12/16/acupuncture-xerostomia-spin-negative-study/

Anorexia and cachexia

Candida (thrush) infections

Bario-reflux dysfunction

Mouth and gum sores

Difficulty swallowing

Esophageal stricture

Lymphedema

Osteoradionecrosis

Stiffness in the jaw

Mucositis

Myelodysplastic syndrome

Neutropenia

Nausea

Hair loss

Periodontal issues

Stomatitis/fibrosis

Trismus

Dysphagia

A type of swelling called lymphedema

Tooth decay (dental caries)

Carotid artery stenosis


Chest area (in the case of HPV+ cancer, this would generally be to treat metastases)

Difficulty swallowing

Shortness of breath

Breast or nipple soreness

Shoulder stiffness

Cough, fever, and fullness of the chest, known as radiation pneumonitis. This happens between 2 weeks and 6 months after radiation therapy.

Radiation fibrosis, which causes permanent lung scars from untreated radiation pneumonitis. The radiation oncologist knows how to lower the risk of fibrosis.

Stomach and abdomen. Radiation therapy aimed at the stomach or abdomen may cause these side effects:

Nausea and vomiting

Diarrhea

These symptoms will likely disappear after treatment. And your doctor can prescribe drugs to manage these side effects. Making changes to your diet may also reduce your discomfort.

Pelvis (covers anal cancer, penile cancer, and cervical, vaginal, and vulval cancers

Diarrhea

Rectal bleeding

Incontinence, which is when a person is not able to control his or her bladder

Bladder irritation

Additionally, men and woman may have different symptoms.

Potential side effects for men include:

Sexual problems, such as erectile dysfunction, which is the inability to get or maintain an erection

Lowered sperm counts and reduced sperm activity. This can occur from radiation therapy to the testes or prostate. And it may affect a man's ability to father a child. Learn about ways to preserve your fertility.

For women:

Changes in menstruation, such as having menstruation stop

Symptoms of menopause, such as vaginal itching, burning, and dryness

Infertility, which is the inability to conceive a child or maintain a pregnancy. This may occur if both ovaries receive radiation therapy. Learn about ways to preserve your fertility.

Radiation recall

Radiation recall is a rash that looks like a severe sunburn. It is rare and happens when certain types of chemotherapy are given during or soon after external beam radiation therapy. The rash appears on the part of the body that received radiation. Symptoms may include redness, tenderness, swelling, wet sores, and peeling skin.

Typically, these side effects start within days or weeks of radiation therapy. But they can also appear months or years later. Doctors treat radiation recall with medications called corticosteroids. Rarely, you may wait until the skin heals before continuing chemotherapy.

Source: Side Effects of Radiation Therapy. Cancer.net

If your curious to learn about the history of the masks used to immobilize the heads of head and neck cancer patients, read here.

This article supports what many cancer survivors will tell you: where you get treated really matters. The study was focused just on survival of those diagnosed with head and neck cancers, the majority of which are HPV positive. For some of us, there may be little choice as to where we can go, but for others, if you have a choice, survival is linked to the type of place you get your treatment at. Race/ethnicity, socio-economic status, and the type of insurance also correlate with the type of place at which care is received.

Carey, R.M. et al Association of Type of Treatment Facility With Overall Survival After a Diagnosis of Head and Neck Cancer. JAMA Netw Open. 2020;3(1):e1919697. doi:10.1001/jamanetworkopen.2019.19697 FREE Download

Keeping track of your appointments as a cancer patient can be a challenge. A company, Jasper, has developed a specialized phone app that helps cancer patients plan appointments and keep track of a number of things. I’m sharing that such an app exists, but am neither suggesting or discouraging you from using it. It may be helpful in allowing you to help plan out your care routine, but I also see that it’s set up to recommend products and services that may, or may not be helpful to you. Check it out if you’re interested, but buyer beware. You need to sign up for the app before you can get a good look at how it operates.

This is a topic that gets considerable debate in the oncology community. It’s well established that conventional treatments in treating these oral cancers using chemotherapy and radiation are very toxic and can be very debilitating for patients quality of life. The other side of the coin is that these treatments can be curative, but often do so at a substantial cost to the patient. There’s hope, backed up by numerous ongoing clinical trials, that the doses of chemotherapy and radiation can be reduced so that there is less harm to the patient, but at the same time preserving excellent cure rates.
I’m not a doctor, and even if I was, the decision to try dose de-escalation therapy needs to be decided on a case by case basis. For those of you who want to dive deep into the arguments on both sides, check out this article, preferably with your doctor:
Wirth et al Point/Counterpoint: Do We De-escalate Treatment of HPV-Associated Oropharynx Cancer Now? And How? 2019 ASCO EDUCATIONAL BOOK https://doi.org/ 10.1200/EDBK_ 238315 FREE Download
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Here’s another editorial about the various trials that are being done in dose de-escalation therapy, and I’ll share one thought from the article: “The landscape of treatment options for HPV-positive OPSCC somewhat mirrors that for low-risk prostate cancer—so many options, all of them seemingly promising, making the decision-making process incredibly confusing and difficult. ”
Chundury, A. et al. Radiation Dose De-Escalation in HPV-Positive Oropharynx Cancer: When Will It Be an Acceptable Standard of Care? J. Clin. Oncol. 2021 FREE Download 10.1200/JCO.20.03128

This editorial follows the publication of this article: Yom, S.S. et al Reduced-Dose Radiation Therapy for HPV-Associated Oropharyngeal Carcinoma (NRG Oncology HN002). DOI: 10.1200/JCO.20.03128 Journal of Clinical Oncology 2021. FREE Download

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A report on the results from a key dose deescalation trial was released on Sept. 30, 2024. Sadly, the results were not good news for patients. Researchers looking to de-intensify radiation treatments for people with early-stage, HPV-associated oropharyngeal cancer to prevent long-term side effects halted a large, randomized Phase II/III trial after patients in the control arm reached a record high, two-year progression-free survival rate of 98%.

Result from the NRG Oncology HN005 trial were presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting.
In this study, Dr. Sue Yom and her team at the University of California-San Francisco tested two lower-intensity treatment regimens against a control arm of more standard chemoradiation for people with HPV-associated, locoregionally advanced oropharyngeal squamous cell carcinomas. A total of 382 patients were randomly assigned to one of three treatment arms:

Usual radiation dosing (70 Gy total mildly accelerated over six weeks) combined with cisplatin chemotherapy
A reduced radiation dose (60 Gy total over six weeks) combined with cisplatin
A reduced radiation dose (60 Gy total mildly accelerated over five weeks) combined with an immunotherapy drug, nivolumab, in place of chemotherapy.

Dr. Yom explained that a preplanned analysis would be triggered for futility when 11 events were reported between a combination of the control group and one of the experimental groups. The phase 3 trial would proceed either if one of the experimental groups did not trigger a futility analysis or at the end of phase 2.

The first futility analysis occurred at a median follow-up of 1.1 years, with nine of the 11 required PFS events occurring in group 2 and two in group 1. The estimated hazard ratio (HR) was 4.34, exceeding the preset boundary of noninferiority of HR <2.4. Group 2 was removed from the protocol, and randomization continued for groups 1 and 3.

The second futility analysis was triggered, at a median of 1.7 years of follow-up, after 11 PFS events occurred, with nine of the 11 required events occurring in group 3. The estimated HR was 4.51, again exceeding the preset boundary of noninferiority. Dr. Yom said that accrual would have stopped at this point, but phase 2 accrual was already complete.

At a median follow-up of 2.2 years, the 2-year PFS was 98.1% in group 1 compared with 88.6% in group 2 and 90.3% in group 3. The 2-year locoregional failure rate was 0% in group 1, 6.5% in group 2, and 5.0% in group 3. The 2-year overall survival estimates are 99.0% in group 1, 98.0% in group 2, and 96.1% in group 3.

“These results set a new benchmark for PFS expectations in this population,” Dr. Yom said. “Deintensification studies going forward must evolve to be more selective and more effective if they are going to be competitive in a more challenging population.”

All patients received intensity modulated radiation therapy, and most were male (90.6%), white (87.5%) and never-smokers (79.4%).
The Phase II trial was designed to trigger a futility analysis for each experimental arm after a predetermined number of patients experienced disease progression. These tests showed that neither de-intensified treatment approach met the threshold for non-inferiority compared to the standard treatment, however, and the trial was closed early.

"In very rigorous testing, those experimental arms did not produce equivalent results to the control arm," said Dr. Yom.
"The experimental arms were close to meeting their expected goals, but the patients treated on the control arm had such incredible results that we had an ethical responsibility to halt the study. I believe we have to take stock of this new benchmark and that new trial designs for this disease will need to account for this result."

With a median follow-up of 2.2 years, the two-year PFS estimates were 98.1% following treatment on the control arm, 88.6% after reduced radiation with chemotherapy and 90.3% after reduced radiation with immunotherapy. The two-year overall survival estimates were 99%, 98% and 96.1%, respectively. "I think this study is a good reminder that patients with this disease have really outstanding cure rates after we treat them with contemporary chemoradiation," Dr. Yom said. "At this point, neither of the deintensification options we tested would be appropriate for standard of care use, because you would actually be changing some patients' chance for a cure."

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Some good news to share from the "radiation dose-deintensification" trials for HPV-caused head and neck cancers. Results have just been published for a phase II trial showing that a reduced radiation dose treatment appears to be as effective as standard of care after three years. This treatment involves TORS (robotic surgery) in combination with 50 Gy (low dose) radiotherapy and no chemo. The idea behind this is to improve the quality of life by having less damage from the radiation while maintaining high survival benefits. 95% of the patients in the trial were alive and disease free three years after treatment. The trial is continuing.
From the story: “For intermediate-risk patients – those with uninvolved surgical margins, less than five involved nodes, and less than 1mm extranodal extension – postoperative radiation therapy at 50 Gy without chemotherapy appears sufficient."

Ferris, F.L. et al Phase II Randomized Trial of Transoral Surgery and Low-Dose Intensity Modulated Radiation Therapy in Resectable p16+ Locally Advanced Oropharynx Cancer: An ECOG-ACRIN Cancer Research Group Trial (E3311) DOI: 10.1200/JCO.21.01752 Journal of Clinical Oncology
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Here’s a nice synopsis of ongoing radiotherapy trials for patients with locally advanced HPV-positive head and neck cancers:
Transoral Robotic Surgery Followed by Adjuvant Radiotherapy
Definitive Radiotherapy With Chemotherapy Cetuximab and/or Immunotherapy
Personalized Chemoradiation Therapy Based on Hypoxia Imaging
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The news above about dose-de-escalation (or deintensification) looked promising. However, more recent data from 2023 produced the opposite finding. In this study, the radiation dose was dropped from 70 Gy to 60 Gy, and that treatment did NOT pass the non-inferiority threshold:
“NRG-HN005, “A Randomized Phase II/III Trial of De-intensified Radiation Therapy for Patients with Early-Stage, p16-Positive, Non-Smoking Associated Oropharyngeal Cancer,” is temporarily closed to accrual as broadcasted on February 03, 2023.
The results of the scheduled interim futility analysis comparing experimental Arm 2 (60 Gy radiation plus cisplatin) to the control Arm 1 (70 Gy radiation plus cisplatin) for the randomized phase II portion of the study, showed that Arm 2 did not achieve the non-inferiority threshold per the protocol’s statistical analysis plan.”
To see details of the trial, click here.