HPV Cancer Resources

Helpful Information for Parents, Patients, Partners, and Providers

Helpful Information for Parents, Patients, Partners, and Providers

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Hot Topics for HPV+ Patients and Their Caregivers - FAQ

There are a number of topics that seem to come up all the time in HPV cancer patient forums, at least in the one I'm in, which is focused on oropharyngeal (throat and back of mouth) cancers. I've posted a number of these below along with my understanding of where things currently stand on the subject. That may change over time as new data is developed, at which time I'll try to update my take on these various issues. Keep in mind that I'm NOT a doctor, and these simply reflect my thoughts about these subjects. Discuss any of these topics that you're concerned about with your doctor(s) for more information.

  • (1) How Do You Get An Oral HPV Infection?

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    WARNING: the answer below contains info about sex and sexual practices. If this makes you uncomfortable, please stop reading now.

    The short answer to the question above is: very likely from oral sex.

    HPV is a sexually transmitted infection (STI) and the most common one by far. It’s estimated that about 14 million people in the US get infected every year, and about 90% of adults will be infected with the virus during their lifetimes.

    Besides sex, the information available on catching these infections is murky, to say the least. Can it be passed sharing a bottle of soda with an infected friend? Most researchers would say probably not. How about by casual kissing (e.g. a quick peck on the lips)? Most researchers again would say that’s unlikely. How about deep (“French”) kissing? Again, that may be more likely, but most researchers wouldn’t say that causes many cases either.

    Why is it so hard to answer this question clearly? The answer is human behavior. In order to get an answer to this question, you’d have to compare people who limited their “interactions” with others to “just kissing”, and compare their infection rate with people who either did “no kissing at all”, or “kissing with additional more intimate activities.” It would be very difficult to identify a group of people who limited their intimacies to kissing. With most people, things usually move along from kissing to other activities. Without being able to do this comparison study, it’s difficult to say with any assurance that HPV can be transmitted by other methods (i.e. kissing or the shared soda bottle).

    Many of you have heard that the incidence of HPV+ oral cancer is much higher in men than women, and this is true. Between four and five men will develop an HPV+ oral cancer for every woman that does. Why is this tilted so much in this direction? It’s thought to be because it’s much easier for women to transmit the virus from their genitals than men. Why would that be? It’s likely due to the fact that wet, moist tissues (e.g. vaginas) provide a more “easy to transmit the virus environment” than drier tissues (e.g. penises). Condoms provide some protection against HPV infections, but they are not fully protective because secretions may get around the barrier the condom provides. It’s possible that fingers or sex toys can also transmit HPV infections to others.

    The only other tissue type that HPV causes cancer in that is shared by men and women (besides oral cancer) is anal cancer. In this case, HPV+ anal cancers are much more prevalent in women than men (by about 2 to 1). Is this because more women have anal sex? Not necessarily. The distance from the vagina to the anus is pretty close, and it’s thought that “fluids” may transfer the infection from one place to the other. One of the best explanations I’ve read about this compared vaginal secretions to glitter. You know how someone can mail you a holiday card with glitter on it, and later you find that glitter all over your house? It’s sort of like that.

    There should be no shame in getting an HPV infection as they are incredibly widespread. In general they’re only problematic if they cause either genital warts or cancer. Early detection for cancer is very important, especially for cervical cancer. One hundred years ago, the Pap exam had not yet been invented yet. That happened in 1928, although the exam didn’t become widespread in the US until the 1950s. By the way, Pap does not refer to papillomas; it’s actually a shortened version of the name of the Greek doctor who developed the test, George Papanicolaou. In 1923, the number one cause of cancer deaths in women in the US was cervical cancer. The Pap test revolutionized the discovery of early pre-cancers of the cervix while they were readily treatable. As a result, cervical cancer now ranks 14th on the list of cancer deaths for women in the US. Sadly, in places around the world where the Pap test is not widely available, the cervical cancer incidence is still very high. Worldwide, HPV infections cause about 1% of all cancers in men, whereas for women it’s closer to 9%. The vast majority of those cases are cervical cancer.

    Since the HPV vaccine can prevent cervical cancer (we have solid data on this), as it gets used more, the incidence of cervical cancer is expected to drop steadily. Australia was the first country to adopt the HPV vaccine, and the incidence of cervical infections and cervical cancer there is plunging. It may be essentially eliminated in the next decade. HPV-caused oral cancer rates are also expected to decline eventually, but that will take much longer for two reasons. One is that many parents think that boys don’t benefit from the vaccine, which of course they do. The other one is that cervical cancers develop much faster than oral HPV cancers (I don’t know why that is). The median age for men and women to be diagnosed with an oral HPV cancer is about 61 to 63; the median age for cervical cancer diagnosis is 49 (and there are many cases that occur while women are in their 20s or 30s).

  • (2) Is There A Benefit To Getting Vaccinated Against HPV If You Already Have HPV?

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    The answer is: maybe. Possibly. It depends mostly on your social situation (i.e. your love life). How likely is it that you might run into a new partner who is infected and could transfer that infection to you? If you’re monogamous or simply no longer engaged in sexual activities, you should be all set. If you’re not, here are some things to think about.

    Vaccination will not eliminate the infection already inside you. Inside your cells, the virus can exist in several states. It can remain free floating in the cell, or it can actually integrate itself tightly and permanently into your DNA. It can cause cancer from either location. The antibodies generated in response to the vaccine won’t attack already infected cells. So what good would vaccination do?

    It could prevent you from being infected with a different strain of HPV. There are hundreds of strains of HPV circulating around the world. Most don’t too much of note, although they can cause benign skin warts on your hands or feet. A few can cause genital warts. And a relatively small number of them can cause cancer. The current vaccine used in most countries is Merck’s Gardasil 9, which offers protection from the two most prevalent strains that cause genital warts as well as seven “high-risk” strains that can cause cancer.

    No vaccine is perfect, but the Gardasil 9 vaccine has a very strong safety and effectiveness record. Keep in mind that there are still many “regular” and cancer-causing strains of HPV that the vaccine will not protect you from. The strains chosen for the vaccine are the ones most commonly circulating, so the vaccine will protect you from those. How likely are you to run into one of these other cancer-causing strains? Not too likely, but it also depends on where you live (or more properly, where you partner lives now or lived before). The distribution of cancer-causing strains varies between areas e.g. different continents. Some of the ones common in Africa or Europe you might not run into here, and vice versa. There’s no way to predict which strains you might come across because you may not know where your partner has been, or who their previous partners have been.

    Considerations: are you planning on getting back in to the dating pool? This might be a reason to get the vaccine. In case you were wondering, it is indeed possible to be infected with multiple strains at the same time. The vaccine could save you from getting genital warts or another cancer-causing strain. Keep in mind that being infected with a cancer-causing strain doesn’t mean you’ll get cancer from it. Most people won’t. One way we know this is because it’s estimated that some 14 million people in the US are infected with HPV every year. Compare that with the fact that some 35,000 people in the US will be diagnosed with an HPV-caused cancer each year (that’s in all tissues, not just oral cancer). This huge disparity in numbers tells us that not everyone will get an HPV cancer. It’s actually a relatively rare event.

    If you’ve had an HPV cancer, this means that your immune system failed to mount a sufficient response to the virus. Most people who are infected with HPV clear that infection within two years. People in our group failed to do so. It’s difficult to say if that means you won’t clear an infection with a different strain, but it seems reasonable to think that you might not. And just because you didn’t clear this second infection doesn’t mean the new strain will cause cancer (if it’s actually a cancer-causing strain). Again, most people infected don’t get cancer. The HPV virus is not sufficient on its own to cause cancer. Other changes need to take place inside your cells in order for an HPV-infected cell to become cancerous. And those changes may not happen within your cells.

    The vaccine is now approved in the US up to age 45. This means the cost of it will be covered by most people that have insurance and are that age or younger. If you don’t have health insurance and you’re over 45, you may need to pay for it yourself if you can get your doctor to prescribe it.

    One other interesting thing about HPV infections is that they can be discordant in terms of the tissues affected. For example, if you have an oral HPV infection, you might think that means you also must have an HPV infection in your genitals. Turns out that’s not the case. You could have an infection in your mouth and not have one in your genitals. Or vice versa; you can have one in your genitals but not in your mouth (that obviously wouldn’t apply to the patients in this group). The virus doesn’t travel inside your body. And HPV infections are not limited to heterosexual couples. Same sex couples run these same risks as heterosexual couples do.

    One question I don’t know the answer to: would being vaccinated inhibit your ability to spread HPV to partners? As far as I can tell, the answer is not known. A study was begun in 2020 to look into this, but it has not been completed as far as I can tell. Here’s the reference: MacCosham A, El-Zein M, Burchell AN, et al. Transmission reduction and prevention with HPV vaccination (TRAP-HPV) study protocol: a randomised controlled trial of the efficacy of HPV vaccination in preventing transmission of HPV infection in heterosexual couples. BMJ Open 2020;10:e039383. doi:10.1136/ bmjopen-2020-039383

    For more information, read through the FAQ on this page of my website as well as the Epidemiology of HPV Cancers page.

  • (3) What Effect Does Radiation/Chemo Dose De-Escalation Have On Cure Rates?

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    Many of the folks on this page are aware that the standard treatment most people get for HPV+ head and neck cancers is a combination of radiation and chemotherapy (about 5 to 10% get surgery instead; some get all three treatments). The standard treatment can be very difficult to endure (just read the comments posted here every day) because the radiation and the chemo do damage to healthy tissues at the same time they are supposed to be getting rid of the cancer cells.

    Could the same results be achieved by lowering the dose of radiation and/or chemo so that there’s less toxicity to the patient?

    The answer to this question is complicated. First, what do we mean by “same results?” The standard measure of how effective cancer treatments are is something called the five-year survival rate. Essentially, this is calculated by asking: out of a group of 100 patients, how many would we find are still alive five years after their treatment? Different cancers have very different five-year survival rates. In the case of HPV+ head and neck cancers, the numbers are very good. About 90 to 95 of the 100 patients are currently expected to be alive after five years. And this doesn’t mean that 5 to 10 patients died of their cancer. It just means that they aren’t alive after five years (they could have died in a car crash or had a stroke). Compare this to pancreatic cancer, where the five-year survival rate is only about 5 patients alive out of 100 at five years.

    What this means is that any “new” treatment for HPV+ head and neck cancers should achieve a five-year survival rate in this same range, about 90 to 95%, to be considered as good. So if a lower dose of radiation, for example, produced this result, it would likely become the new standard of care IF it had less “side effects” (which might mean fewer problems with swallowing, producing saliva, or tissue damage, for example). Ideally, it might achieve closer to a 100% response, but that’s not required if the lower dose has less “side effects” and causes collateral harm to the patient.

    What happens if the new treatment clearly causes less “side effect” damage, but now shows a five-year survival rate of only around 80%? Now we are looking at trade off issues: patients would likely have less damage done, but now fewer people out of 100 will live as long as five years. Patients might be offered this choice, or they may not. And your willingness to try the reduced dose treatment might depend on your priorities.

    Would you risk a greater chance of NOT surviving to have an easier to tolerate treatment? That’s a decision only a patient can make.

    The fact that the standard measure is the “five-year survival rate” means that if one wants to do a clinical trial to see if a proposed “lower dose” treatment works as well (or better) than the standard of care, it might take more than five years to figure that out. Five years for the trial, plus time beforehand to recruit patients, and time afterwards to gather and generate the data. Along the way it may become apparent that patients are dying at a faster rate than with the standard of care treatment, at which point the trial would be stopped because it would be unethical to add more patients to the new reduced dose protocol. In the case of cancers with low survival rates, trials can stop early if it becomes clear that fewer patients are dying (put another way, the new treatment is better than the standard of care.

    Clinical trials are indeed underway to find some radiation/chemo treatment plan that is less toxic AND has a similar, if not better, five-year survival rate. These trials obviously take a lot of time, and they also take a lot of money to do properly. That money would likely have to come from the government, the hospital, or wealthy donors because drug companies would not sponsor or pay for such a trial (there’s no financial benefit to them for doing so).

    Bottom line: everyone would like to see a “kinder and gentler” treatment for this cancer, and clinical trials are underway, but getting a clear answer will take time.

    You should also know that other types of therapies are being tested that might replace radiation/chemo treatments, but as yet none are as good or better than the standard of care. That's a topic for another day.

    In the meantime, here's an excellent FREE review of where things stand with dose-deescalation therapies from the summer of 2023:
    Allen Chen. De-Escalation Treatment for Human Papillomavirus–Related Oropharyngeal Cancer: Questions for Practical Consideration. ONCOLOGY Vol 37, Issue 7, 281-287 (2023)
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    There are clinical trials being done that use PET scans done in the middle of treatment as a biomarker for deciding whether or not patients may respond equally well to a lower dose of radiation. We don't know yet whether or not this approach will pan out or not. One of these is described below.

    This study looked at FDG-PET–Guided Deintensification of Radiotherapy in HPV+ cancer patients. Note: the data below is from a meeting abstract, not a published, peer reviewed journal article. Discuss this with your doctor if you are interested in learning more about this.

    “FDG-PET may be a reliable predictive biomarker to selectively de-escalate the radiation dose in early-stage HPV-positive disease…. There were few locoregional recurrences,” Dr. Regan said.

    The study enrolled 89 patients with stage I–II HPV-associated tumors with known avidity on FDG-PET imaging. All patients had a radiation plan for 70 Gy to gross disease and 56 Gy to elective nodal regions, to be given concurrently with carboplatin and paclitaxel. A mid-treatment PET was planned to assess response, which determined additional treatment. Those patients with at least a 50% reduction in metabolic tumor volume stopped treatment at 54 Gy to gross disease, whereas the others completed the entire course of 70 Gy. The primary endpoint was noninferiority of 2-year locoregional recurrence in the entire cohort, compared with an institutional historical control.

    Primary Endpoint Met

    Of the 84 patients who underwent mid-treatment evaluation, 48 continued to standard therapy, and 36 met criteria for de-escalation. At a median follow-up of 32 months, the study met its primary endpoint, demonstrating a 2-year locoregional recurrence rate of 6.8% for the entire population. By cohort, the 2-year locoregional recurrence rates were 4.6% for patients treated throughout with 70 Gy and 9.4% for those de-escalated to 54 Gy. “Of note, these rates represent only two and three locoregional failures each, respectively. The broad, overlapping confidence intervals preclude any definitive comparison of these two different cohorts,” Dr. Regan said. The 2-year progression-free survival rate was 87% with 70 Gy (four events, one likely treatment-related death) and 84% with 54 Gy (four events). After initial salvage therapy for the eight patients with recurrences (locoregional or distant), three of four treated with 54 Gy have no evidence of disease, and one is still on treatment, whereas with 70 Gy, two of four patients have no evidence of disease, one is on treatment, and one has died.

    Weight Loss, Swallowing, and Quality of Life

    Median weight loss from baseline to 3 months after radiotherapy was 23 lb in the standard-treatment group and 11 lb in the de-escalated group (P < .001), and the percentages lost were 12.6% and 6.0%, respectively (P < .001). A nasogastric tube was required by 16% and 11%, respectively (P = .5), and there was no appreciable change in the penetration-aspiration scale from baseline in either group. The University of Washington Quality-of-Life Total and Pain Subscale scores as well as the Functional Assessment of Cancer Therapy–Head & Neck Total and Cancer Subscale scores significantly improved at 1 month, above the minimal clinically important difference threshold (0.5 standard deviations), in the de-escalated cohort. Most patients in both cohorts returned to baseline at 1 year.

    Full details can be found here. Note that these trials were NOT open to all patients. Particular criteria had to be met, as defined below.
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    In 2024, a new study supported the idea of dose-deescalation treatment for HPV+ head and neck cancers.The MINT trial enrolled 58 patients with clinical stage I–III, HPV-positive oropharyngeal squamous cell carcinoma (or with a positive neck node with an unknown primary) who underwent surgery and selective neck dissection. Then, 54 patients were then stratified by pathologic risk into one of the following three treatment arms based on pathology:

    Arm 1: high-risk pathology (extranodal extension and/or positive margins): De-escalated postoperative adjuvant chemoradiotherapy with cisplatin at 100 mg/m2 for one dose plus 42 Gy of radiotherapy over 21 fractions (n = 20)

    Arm 2: intermediate-risk pathology (lymphovascular invasion, perineural invasion, at least two positive nodes, at least one positive node → 3 mm, T3 or N2 disease): De-escalated postoperative adjuvant radiotherapy with 42 Gy over 21 fractions (n = 30)

    Arm 3: highest-risk pathology (cT3–pT4): Standard-of-care treatment with cisplatin at 100 mg/m2 for three doses plus 60 Gy of radiotherapy delivered concurrently (n = 4).
    Dr. Thorstad reported the results of the two experimental arms involving de-escalated chemoradiotherapy (arm 1) and de-escalated radiotherapy (arm 2). The primary hypothesis was that de-escalated treatment would result in less weight loss, which is a quantitative surrogate of the severity of mucositis. Recurrence rate, progression-free survival, and overall survival were also endpoints. The recurrence rate was deemed acceptable if the 95% upper limit of the confidence interval (CI) was ≤ 20%.

    Results With De-escalation. The data below is from a meeting abstract, not a published, peer reviewed journal article. Discuss this with your doctor if you are interested in learning more about this.

    The mean percent weight loss during de-escalated postoperative adjuvant chemoradiotherapy was significantly less than in a similar historical cohort treated conventionally: 4.9% vs 7.4% (P = .0003). The mean percent weight loss during de-escalated radiotherapy was 3.18%, Dr. Thorstad reported.

    At a median follow-up of 50 months, there were 2 recurrences (distant alone) in the 20 patients in arm 1 (de-escalated chemoradiotherapy) at 12 and 19 months after treatment. There was one recurrence (both regional and distant) in the 30 patients in arm 2 (de-escalated radiotherapy) at 22 months. The one death in arm 2 was a patient known to be disease-free 3 months earlier, he added.

    These events amounted to recurrence rates of 10% in arm 1 (95% CI = 1.2%–31.7%) and 3.3% in arm 2 (95% CI = 0.1%–17.2%). At 4 years, 90.0% and 90.1%, respectively, were progression-free, and 100% and 94%, respectively, were alive. “Note the 95% confidence interval in arm 2 was < 20% as an upper limit [for significance], but we did not achieve that in arm 1, possibly because of the low patient numbers,” Dr. Thorstad commented. “We are looking at a future trial to increase the confidence with the arm 1 [approach] and perhaps at randomly assigning patients from arm 2 to an even lower radiotherapy dose.”

    Thorstad WL, Jackson RS, Oppelt P, et al: Long-term efficacy of risk-directed, de-escalated post-operative adjuvant therapy for surgically resected locally advanced, human papillomavirus-positive oropharynx squamous-cell carcinoma: A non-randomized, multi-arm phase 2 trial. 2024 Multidisciplinary Head and Neck Cancers Symposium. Abstract 14. Presented March 1, 2024.
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    The second study looked at FDG-PET–Guided Deintensification of Radiotherapy in HPV+ cancer patients.

    “FDG-PET may be a reliable predictive biomarker to selectively de-escalate the radiation dose in early-stage HPV-positive disease…. There were few locoregional recurrences,” Dr. Regan said.

    The study enrolled 89 patients with stage I–II HPV-associated tumors with known avidity on FDG-PET imaging. All patients had a radiation plan for 70 Gy to gross disease and 56 Gy to elective nodal regions, to be given concurrently with carboplatin and paclitaxel. A mid-treatment PET was planned to assess response, which determined additional treatment. Those patients with at least a 50% reduction in metabolic tumor volume stopped treatment at 54 Gy to gross disease, whereas the others completed the entire course of 70 Gy. The primary endpoint was noninferiority of 2-year locoregional recurrence in the entire cohort, compared with an institutional historical control.

    Primary Endpoint Met

    Of the 84 patients who underwent mid-treatment evaluation, 48 continued to standard therapy, and 36 met criteria for de-escalation. At a median follow-up of 32 months, the study met its primary endpoint, demonstrating a 2-year locoregional recurrence rate of 6.8% for the entire population. By cohort, the 2-year locoregional recurrence rates were 4.6% for patients treated throughout with 70 Gy and 9.4% for those de-escalated to 54 Gy. “Of note, these rates represent only two and three locoregional failures each, respectively. The broad, overlapping confidence intervals preclude any definitive comparison of these two different cohorts,” Dr. Regan said. The 2-year progression-free survival rate was 87% with 70 Gy (four events, one likely treatment-related death) and 84% with 54 Gy (four events). After initial salvage therapy for the eight patients with recurrences (locoregional or distant), three of four treated with 54 Gy have no evidence of disease, and one is still on treatment, whereas with 70 Gy, two of four patients have no evidence of disease, one is on treatment, and one has died.

    Weight Loss, Swallowing, and Quality of Life

    Median weight loss from baseline to 3 months after radiotherapy was 23 lb in the standard-treatment group and 11 lb in the de-escalated group (P < .001), and the percentages lost were 12.6% and 6.0%, respectively (P < .001). A nasogastric tube was required by 16% and 11%, respectively (P = .5), and there was no appreciable change in the penetration-aspiration scale from baseline in either group. The University of Washington Quality-of-Life Total and Pain Subscale scores as well as the Functional Assessment of Cancer Therapy–Head & Neck Total and Cancer Subscale scores significantly improved at 1 month, above the minimal clinically important difference threshold (0.5 standard deviations), in the de-escalated cohort. Most patients in both cohorts returned to baseline at 1 year.

    Regan SN, Rosen BS, Suresh K, et al: FDG-PET-based selective de-escalation of radiotherapy for HPV-related oropharynx cancer: Results from a phase II trial. 2024 Multidisciplinary Head and Neck Cancers Symposium. Abstract 16. Presented March 1, 2024.
  • (4) Proton vs. Photon (X-rays). Which Radiation Method Is "Better"?

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    The short answer is: we simply don’t know. Let me start off by saying that most of the people here are not going to actually have a choice about this. Most people are going to get standard photon (X-ray) treatments (sometimes called external beam therapy) if it’s decided that their cancer needs irradiation to eliminate it. It’s been the standard treatment for a long time, often in combination with chemo. But there’s a new kid on the block: proton beam radiation. I’m not going to focus on the physics here to explain the differences, but basically proton radiation can provide more destructive energy to the tumor. Use the link below if you’d like to learn more.

    X-ray machines are (relatively) small. Think how small the ones are at the dentist’s office. The ones used on head and neck cancer patients are much more sophisticated, with mechanisms that allow them to move in three dimensions using a computer-controlled beam that hits exactly where the radiation oncologist wants it to hit with the rays. In contrast, proton beam machines are enormous. They, too, are computer controlled and can direct the beam in a very precise manner. Building them is very expensive, which is one reason why there are so few of them, and why proton radiation treatments costs more than X-ray irradiation. Where I live, the one proton radiation facility in the city went bankrupt (but never stopped operating) a few years ago.

    So why did they develop proton beam therapy treatments? The idea is that the beam can be controlled in a way that’s more precise than with X-rays, specifically in how deep the rays penetrate. The idea is to try to limit the damage caused by rays hitting normal tissues after passing through the tumor. This should lead to a better quality of life. There is some data that’s been developed that suggests that the proton beam really is less destructive of normal tissue than standard X-ray therapy. As I explain below, that may or may not be a good thing.

    Here’s the dilemma, and it’s essentially the same one I covered in dose de-escalation trials. With radiation, there are two competing issues. Can you do less damage to tissues you don’t want to hit? That’s important for your quality of life, but more important (at least to many of us) is whether or not the radiation beam will destroy all parts of the tumor.

    Once again, the five-year survival rate is the key measure of success here. The proton beam may cause less short term damage to surrounding tissues, but that may come at the cost of being less effective in killing all of the cancer cells. That in turn could reduce overall survival rates for patients. Clinical trials are being done with the proton machines to compare them to X-rays, but we just don’t know yet if they can provide an equal or (hopefully) better survival benefit while reducing off target damage. Yes, once again it’s about potential trade offs.

    In the US, most people have their cancer treatments paid for by health insurance that they get through their jobs. The health insurance companies generally will pay for therapies that have been demonstrated to have an actual health benefit and are the “standard of care.” At this point many of these companies regard proton therapy as “experimental” in treating head and neck cancers, and therefore they won’t pay for it. Wealthy patients may decide they want to pay for it on their own out of pockets (if recommended by their doctors), but many people will not be able to afford this. Patients without health insurance are in a bad situation period when it comes to cancer (or any other) healthcare treatment. If and when proton radiation shows that it really is better than photon (X-rays), it will likely become the standard of care, and health insurance companies should pay for it then.

    Bottom line: we don’t yet know whether or not proton will supplant photon as the radiation of choice. And since it’s they’re so expensive, proton machines will still be in limited supply for some time.

    Those of you wanting more information can look at this page of my website that explained head and neck cancer treatment options.
  • (5) The NavDx Test For HPV+ Cancer Cells In Your body. Is It Useful?

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    The concept here is pretty straightforward. Develop a test that can figure out if you do, or do not, have any HPV+ cancer cells in your body. This information can then be used to determine if you need more treatment, or if you have been effectively “cured” by the treatment you’ve already had.

    Let’s spend a moment to look at the test. It works by quantifying fragments of tumor-specific DNA shed by cancer cells into the blood. This means it’s looking for HPV+ cancer cells, not just cancer cells in general. The test would not find kidney or stomach or prostate cancer if you have it (but it should find cervical cancer since that is caused by HPV). Follow the link at the bottom of the page if you’d like more details.

    So the key question here is: how accurate is the test? When you’re making cancer treatment decisions using such a test, it needs to be not just good, not just great, but pretty darn near perfect. And the test could give a wrong answer in one of two ways: it could say that cancer cells are present when they’re actually not (a false positive), or it could say that you are cancer free when you’re not (a false negative). Relying on either of these wrong results would be problematic, which is a polite way of saying disastrous for a patient. With a false positive, you may get additional treatments that you didn’t really need (not to mention some anxiety as well). With a false negative, you would walk away from having additional treatments when you actually did need them, and the cancer cells would continue to grow in your body, and that’s not going to end well. It’s this need for incredible, ultra-dependable accuracy that makes developing such a test very difficult.

    Another thing to think about is the sensitivity of the test. How many cancer cells do there need to be for the test to detect them? Keep in mind that the average human body has about 30 TRILLION cells in it. So finding a small number of cancer cells is a very daunting task. There’s one other key point to keep in mind about a positive test that is really, truly positive. The test tells you that you have cancer cells in your body, but it doesn’t tell you WHERE they are. In your tonsil? Lymph node? Lung? Knowing you have cancer cells is good, but finding out where these cells are lurking can be a challenge. Why? Because the sensitivity of tests that show where cancer cells are located (i.e. PET scan) may be less sensitive than the NavDx test that tells you the cancer cells are hanging out somewhere. In order to attack this small number of cancer cells (with surgery or radiation, for example), you need to know where they are. This dilemma could be resolved by retesting you from time to time with the NavDx test, and when the numbers have gone up sufficiently (whatever that amount is), then doing a PET scan once more. While you’re waiting you might be living in a state of high anxiety.

    A study was done that ended in 2024 that looked at whether or not the NavDx could be clinically used to identify patients who had minimal residual disease. The study ended early because of a failure to meet the primary endpoint of the study. A second cohort study is still ongoing that "is evaluating de-escalation of radiotherapy and chemotherapy in patients with positive margins (< 3 mm) or extracapsular extension."

    The NavDx test is not the only test that has been or is being developed to detect circulating HPV+ cancer cells. You can find a sampling of some of the other not-ready-for-prime-time tests on the page below of my website.

    Bottom line: at present the NavDx test has some utility, but it’s not accurate enough yet that a doctor would rely solely on this test to determine that one is really cancer free. It’s this clinical uncertainty that prevents this test from being as helpful as people would like it to be. Hopefully the test gets better. Check with your doctor if you have more questions about this. The NavDx test is being covered by Medicare as of Nov. 30, 2023.

    More details about this and other HPV+ cancer screening tests can be found on this page of my website (look both at this main page, and at the info in FAQ2 here).

    Note that the NavDx test was designated as an Advanced Diagnostic Laboratory Test in April 2024. This designation is not related to the accuracy or other characteristics of the test. Rather, it simply means that the provider of the test has been designated the sole provider of that test, and the designation is related to payment costs and reimbursements. So it's a financing thing, not a science issue.

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    A 2024 study looked at the utility of preoperative circulating tumor tissue-modified viral human papillomavirus DNA (TTMV-HPV DNA) levels in predicting human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) disease burden.

    This was a small study of only 70 patients who were scheduled for TORS to remove their tumors. The researchers found that pre-operative levels of TTMV-HPV DNA were quite variable, and did not appear to be associated with tumor size or other tumor characteristics.

    Lam, D. et al. Preoperative Circulating Tumor HPV DNA and Oropharyngeal Squamous Cell Disease. JAMA Otolaryngol Head Neck Surg. Published online April 4, 2024. doi:10.1001/jamaoto.2024.0350
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    Can using the NavDx test be cost effective?
    One analysis suggests that's the case. The total cost of five years of post treatment surveillance using CT scans and back of throat scopes was estimated to cost the medical system $69K.
    Substituting the NavDx test for CT scans reduced the cost down to about $40K.

    "Of the p16+ OPSCC patients (n = 214), 23 had confirmed recurrence (11%). Standard work-flow model determined 72 imaging studies and 2198 physical examinations with FL were needed to detect one recurrence. Potential individual patient cost reduction during surveillance was 42%."
    Lin, M.G. et al Novel HPV Associated Oropharyngeal Squamous Cell Carcinoma Surveillance DNA Assay Cost Analysis. Laryngoscope (2023) FREE download. https://doi.org/10.1002/lary.30701

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    The NaxDx test is just one of a number of tests that are in development to allow the earliest detection of cancer. Some use blood, some use urine, some use other body fluids. Researchers are hoping that their tests can help identify as many as 50 different types of cancer with a single blood test. The article below describes a number of these other tests in development, for those of you who are interested in the subject. The article does a very nice job outlining the pitfalls and problems that need to be overcome before these are ready to be widely used on patients. “It’s safe to say that the technology is not well enough developed to be marketed,” Ruth Etzioni, PhD, a biostatistician at the Fred Hutchinson Cancer Center’s Public Health Sciences Division, said in an interview.

    Rita Rubin. Questions Swirl Around Screening for Multiple Cancers With a Single Blood Test. Journal of the American Medical Association. March 15, 2024. doi:10.1001/jama.2024.1018

    Here's a more recent article from mid-2024 that covers much of the same territory. Blood based cancer screening still presents risks, and the overall benefits are unfortunately still unclear.
    Sanket S. Dhruva and Rita F. Redberg Blood tests for cancer detection aren’t yet ready for prime time
  • (6) Follow Up Screening For Cancer Recurrences

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    We’ve all been there. We finish our treatments and then anxiously anticipate our first (and subsequent) appointments hoping for good news (but also fearing bad news). Scanxiety (anxiety related to what scans will show) is something that I expect most of us have experienced somewhere on our journeys. It’s perfectly natural to be worried as to whether or not your treatment will confer on you the “holy grail” from the mouths of your doctor: your status is NED; no evidence of disease. I hope you all get to experience hearing those words.

    Even after getting a good report, many of us will remain anxious going forward. Suppose the cancer comes back? What if the scan missed something? Both of these things are indeed possible (though not common), and this leaves us feeling unsettled and concerned about what the future might bring.

    As a result of this anxiety, many of us want to have frequent follow up exams from out medical teams. And this leaves people wondering why it is that these exams happen so infrequently once most of us are past the first year or two. Part of our thinking is: even if a follow up exam finds something, I know it will be caught earlier rather than later, and that will lead to a better outcome. So why is it that you don’t get PET/CT scans, or even physical exams, more than once a year?

    There are two major reasons for this. In the case of PET/CT scans, they are both very expensive (so insurance companies won’t want to pay for them), and they also expose you to a great deal of radiation. Radiation damage to your body is cumulative, and the more you get, the more problems that may arise somewhere down the road. A PET/CT scan can expose you to as much radiation as 250 chest X-rays, so these are only done when medically necessary. The PET part of the PET/CT scan raises costs quite a bit since they require the preparation and administration of (slightly) radioactive glucose molecules.

    There’s one other reason that we don’t get regularly scheduled scans or physical exams more that once a year past the first year or two. That reason may surprise you: it’s because these exams rarely find recurrences. In fact, this happens so infrequently that some have called for a stop to doing these yearly follow up exams. Maybe now you’re thinking: wait a minute, that doesn’t make sense. I know people who have had recurrences, and of course we read about them from time to time in posts to this group. Yes, recurrences can and do happen. The key point is: recurrences are most often found when someone experiences some perceived change in their bodies; not in the yearly exams.

    Maybe swallowing feels a little harder. Maybe there’s a small hard lump on the neck that’s felt. Maybe you find your voice is hoarse all the time. In each of these circumstances, the change drives the patient to schedule an exam with their doctor. These are the situations where recurrences are found. So if you had an exam four months ago that was clear, but now find something that is a bit off, go ahead and schedule an exam to check it out. Don’t wait another eight months for your next scheduled exam. The bottom line is that recurrences are most often found from self-surveillance, not routinely scheduled follow up exams. So stay vigilant for any perceived changes, and if you detect something, contact your doctor. If you are not experiencing anything unusual, then in most cases it means that everything really is OK. And even if you do experience something that feels different, it doesn’t mean that your cancer is back. After all, there are many things that can cause your voice to become hoarse that are NOT associated with cancer. Your doctor will help you figure out just what is going on with your body. If you can, try not to worry.

    “Don’t worry” is an easy thing to say, but not so easy to do. I’ve been there, done that. One of the best pieces of advice I got about this is from Tammy von Keisenberg, who likes to remind people “don’t borrow sorrow from tomorrow.” Yes, bad things can happen in the future, but if you’re doing (relatively) OK, enjoy it! Don’t let fear of future problems prevent you from living your life to the fullest!

    FYI researchers are working to develop blood or saliva tests that are sensitive enough to find recurrences without the need of scans or physical exams. Those of you who are interested in learning more about why regularly scheduled follow up exams may not be necessary or helpful can read this article: https://onlinelibrary.wiley.com/doi/abs/10.1002/hed.25425

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    How much screening does it actually take to uncover a single case of HPV+ oral cancer recurrence?

    A recent study looked at this question.
    "Of the p16+ OPSCC patients (n = 214), 23 had confirmed recurrence (11%). Standard work-flow model determined 72 imaging studies and 2198 physical examinations with FL were needed to detect one recurrence.

    Costs for screening each patient for five years were estimated to be ~$69,000.

    Lin, M.G. et al Novel HPV Associated Oropharyngeal Squamous Cell Carcinoma Surveillance DNA Assay Cost Analysis. Laryngoscope (2023) FREE download. https://doi.org/10.1002/lary.30701
  • (7) Are There Other Treatments That Are Known To Be Effective In Curing HPV-caused Cancers?

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    This question comes up often. Sadly, the short answer is no. The thought of having to endure these harsh “standard of care” treatments drives many patients to consider other remedies. Yes, the standard treatments are rough for many people. You can see this in the comments posted here nearly every day. Some people would much rather try other things, including CBD oil, “natural” cures, homeopathy (which simply doesn’t work), dietary supplements, and any number of other agents, including trendy things like ivermectin and hydroxychloroquine instead of the “standard of care”. None of these will cure your cancer.

    Can I prove that these alternatives don’t work? I can’t because I haven’t rigorously tested them in a carefully done clinical trial to determine if they really are effective. The question you really want to be asking is: Is there any solid, reliable evidence that any of these treatments actually do work? It’s highly unlikely that you’ll be able to find any such information. Instead, you’ll find bold claims and hype-filled anecdotal stories (“my cousin had that cancer, took those pills that he bought online, and now he’s cured!”) instead of actual hard data. There are many different kinds of supplements you can buy from online websites, on Amazon, from neighborhood “healers”, or in stores that sell nutritional supplements. Most of them will have a legal disclaimer on the package that will say something like this:

    “These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.”

    This statement is there to protect the seller from being sued by consumers (or their heirs) when the product turns out to be ineffective. There are different types of claims that products can make. The following info is from the Edible Chemistry consulting website:

    “Nutritional claims: These are statements about the general effects dietary supplements, vitamins, and minerals have on diseases known to be caused by nutrient deficiency. For example, “vitamin C prevents scurvy.” These claims do not need to be approved by the FDA (US Food and Drug Administration). But the label must also state how many cases of the disease occur in the United States. In this example, consumers must weigh the risk of getting scurvy against the potential risks of the supplement itself.

    Claims of wellbeing: These are just that – statements such as “makes you feel better.” These claims do not require pre-approval by the FDA.

    Health claims: These are statements about known health benefits of certain compounds. For example, risk-reduction claims such as “folate may reduce the chance of pregnant women delivering an infant with neural tube defects” fall into this category. The FDA must pre-approve all health claims, and requires that they be supported by evidence from scientific studies. Remember that risk-reduction claims are not the same as prevention claims.

    Structure or function claims: These are the most confusing claims made to consumers. They are claims about the effect of the dietary supplement on the structure or function of the body. The FDA published a ruling in January 2000 that explained exactly what kinds of structure or function claims OK for dietary supplements are.

    Dietary supplements may not make any claims regarding the treatment of disease. But the following descriptions and examples are considered structure or function claims that are OK for dietary supplements:
    The product’s mechanism of action (“works as an antioxidant”)
    The product’s effects on cellular structure (“helps membrane stability”)
    The product’s effects on the body’s physiology (“promotes normal urinary flow”)
    The product’s effects on chemical or lab test results (“supports normal blood glucose”)
    Claims of maintenance (“helps maintain a healthy circulatory system”)
    Other non-disease claims (“helps you relax”)
    Claims for common conditions and symptoms related to life stages (“reduces irritability, bloating, and cramping associated with premenstrual syndrome”)””

    Here’s my main takeaway: it’s easy for people to make claims about their products, but much, much harder to collect solid proof that supports that claim. A product may claim to supercharge your immune system, but it can’t promote claims that doing so will help treat, prevent, or cure any disease unless they can actually prove it. These claims are made simply to transfer the money in your wallet into the pockets of the sellers. Many of them are no better than the “snake oil salesmen” from early in the last century.

    Be wary of any dietary supplement or other product that claims to prevent, treat, or cure any type of cancer. Such claims can only be made for products such as pharmaceuticals or treatments that have been proven (by doing multiple clinical trials) that they do what they claim to do. And while we’re on the subject of drugs, no, pharma companies don’t have cures for cancer that they are hiding from the public. Ask yourself: why wouldn’t they sell them, and who are they saving them for?

    For more details, see this info from the Food and Drug Administration.

    A new research paper showed that people who chose to take non-conventional treatments (e.g. vitamins/homeopathy/unapproved drugs/CBD oil) for a number of survivable cancers (nonmetastatic breast, prostate, lung, or colorectal cancer) instead of the “standard of care” were twice as likely to die from their cancers as those who chose the “standard of care.”

    Complementary Medicine, Refusal of Conventional Cancer Therapy, and Survival Among Patients With Curable Cancers. Johnson, S.B. et al

    JAMA Oncol. 2018;4(10):1375-1381. doi:10.1001/jamaoncol.2018.2487

  • (8) How exactly does HPV cause cancer?

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    Before diving into the role that HPV plays in cancer, let’s start by taking a look at how cancers form in general. Cancer is a genetic disease, that is, it’s caused by mutations to the DNA inside your cells. These mutations keep some of the proteins inside your cells from working the way they were meant to work, because the instructions for making these proteins are encoded in your DNA. These mutations occur in a variety of ways. Some happen as part of the normal process of cell division (it’s actually designed by nature to NOT be a perfect process). Some mutations are caused by DNA damaging agents, such as chemicals (called carcinogens) or radiation from X-rays or other sources. Mutations in our DNA tend to accumulate over time as we age. Older folks have many more DNA mutations inside their cells than babies do, which is why the rates of developing different cancers are much higher in older people. This helps explain why of the approximately two million cancer cases diagnosed in the US every year, only 15,000 are cancers in children (that's 0.75 percent). Sometimes these mutations cause cells to continuously divide; the normal brakes on this process are disrupted by the genetic alterations. When this happens, the cells eventually will form a tumor.

    How many of these genetic alterations or mutations are needed to transform a normal cell into a cancer cell? This is a highly variable process. Some of these alterations are extremely powerful and only a single mutation can result in a cell becoming transformed and turning cancerous. The more usual course is that a substantial number of these genetic alterations are required to turn a normal cell cancerous. Could be 25. Could be closer to 50, or maybe even a hundred. Every tumor is like a snowflake; no two are alike. Different mixes of genetic alterations can lead to the transformation process. Some of these combinations are more transformative than others. There are some well-known mutations (genetic alterations) that are seen in many cancers; these alterations may serve as targets that anti-cancer drugs are meant to attack. As cancers divide and grow, they tend to add additional mutations that make the tumors that much more difficult to treat.

    These mutated (or altered genes) receive a lot of attention from cancer researchers. Scientists want to know if any of the changes are necessary to cause cancer (that is, without that change, cancer won’t develop) as well as if they are sufficient (if the change occurs, then the cell will definitely become cancerous). HPV actually fails both of these tests. The vast majority of cancers (such as breast, brain, bladder, kidney, or colon cancer) do NOT contain any HPV. This tells us it’s not always needed to cause cancer. HPV infection is also not sufficient on its own to cause cancer. How do we know this? It’s because only a small percentage of HPV-infected people go on to develop cancer. Most never do. So HPV alone is clearly not sufficient to cause cancer on its own, although it clearly can contribute to the process.

    Most of you know that many cases of head and neck cancers are NOT caused by HPV (instead, they’re associated with excessive smoking and/or drinking). Even though they’re the same kind of cancer (squamous cell carcinoma), these non-HPV head and neck cancers are actually considered a separate disease from those head and neck cancers caused by HPV. These non-HPV cancers are treated in exactly the same way, but it turns out that the HPV-caused head and neck cancers are actually much more treatable (and curable) than those cancers NOT caused by the virus. Exactly why this happens isn’t well understood. HPV infection, even though it helps to make the cells cancerous, also makes them more susceptible to the killing effects of chemo and/or radiation.

    Tumors may simply stay in one place, or they may acquire additional mutations that allow the tumor cells to break off from the main mass and travel (via the bloodstream or the lymphatic system) to distant locations. There, the cells may get stuck and begin the division process all over again and form a new tumor. This process is known as cancer metastasis and is a bad development because cancers are much easier to attack if they are located in a single place.

    So how does HPV cause cancer? Cancer-causing strains of HPV enter our cells and can do one of two things. If your immune system doesn’t clear the infection, the viral particles can simply float around and just hang out in your cells. Alternatively, they can actually insert themselves into the DNA inside our cells in a process known as integration. Sometimes the virus may hang out for long periods of time before it integrates into our cells. Once this happens, the integrated virus begins to make some of the proteins that are contained within it’s own genetic structure. Exactly where the virus integrates into our DNA also plays a role in whether or not the virus can cause cancer. At least two of these viral proteins, E6 and E7, appear to play a role in transforming a normal cell into a cancer cell. As a result of this, a number of biopharma companies are creating drugs to disable these proteins, which may render the cells non-cancerous and leave them open to attack by the immune system. These drugs wouldn’t work on non-HPV cancers, but if they are effective, they should be able to be used to fight all of the HPV-caused cancers, including anal and cervical cancer. I keep track of these clinical trials and will let people know if these actually pan out. It would be a great advance to have another option beside surgery, chemo, and radiation.

  • (9) Is being p16+ the same thing as having HPV-16?

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    The short answer is no. This topic is a bit complicated, but I will explain. There are many different types or strains of HPV that cause cancer. The two most prominent are HPV 16 and HPV 18, with 16 being the most common in the US. This is determined by using a technique known as PCR on a biopsy sample from the tumor. These PCR tests take time to run and get results. So doctors often use something called a surrogate marker (see below) to infer that a cancer is likely to be caused by HPV. However, being p16+ is NOT the same as being HPV 16 positive.

    During surgery, biopsy samples are sent to the pathology lab, where they use a different technique called staining to determine what kind of cancer it is, and if it is likely to be caused by an HPV infection (without doing the PCR test, which can't be done quickly). So the pathologists use what's called a surrogate marker, which is something that essentially suggests that the cancer is caused by HPV but without directly measuring it. We use surrogate markers all the time. If you see someone smiling or appear to be laughing when you watch TV with the sound muted, that smiling and laughing is a surrogate marker for something funny being experienced by the people you are looking at. That there are actual jokes occurring can be inferred by the surrogate marker of the smiling and laughing. p16 is used as a surrogate marker for cancers being caused by HPV because it is quick and easy to measure..

    p16 refers to a protein (hence the p for protein) named p16, which is completely different from HPV 16 (the virus), but if cells are stained and shown to be p16+, that suggests that the cancer is being caused by some strain of HPV (could be 16, or 18, or another strain). It is very unfortunate that p16 is so similarly named to HPV strain 16. The hospital will often do a follow up PCR to confirm that the tumor really is HPV+, because there are times when tumors are p16+ but are actually HPV negative. Put another way, the surrogate marker leads us to a wrong conclusion.

    Does being p16+ guarantee or prove that you are HPV+? The answer is no. There can be a lack of concordance between these two measurements. A new paper in 2023 confirmed that a substantial number of p16-positive patients are actually HPV-negative when tested for HPV DNA or RNA. Why does that matter? It's because the study found that for the one in ten of patients who have discordant HPV results, they saw significantly worsening outcomes compared to those who tested negative in both tests.

    In those cases, 5-year overall survival were:
    81% among double positive tests,
    53% for patients with p16-/HPV+ test
    54% for patients with p16+/HPV- tests for patients

    Your doctor can explain this further.

    Reference: Mehanna, H. et al. Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC): a multicentre, multinational, individual patient data analysis. The Lancet Oncology Feb. 2023
    DOI: https://doi.org/10.1016/S1470-2045(23)00013-X (Free Download)
  • (10) How are cancer suvival rates calcuated, and how long is it until one is considered "cured"?

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    The survival numbers we often see are not a "cure" rate. They are five-year survival rates, which is a standard measure of cancer survival. It allows doctors to compare different types of cancer for lethality. What that means is: for every 100 patients, what percentage of them are still alive five years later? That number incorporates exactly what it says: still alive after five years. If it's not 100%, It doesn't mean that those people died of cancer. They could have had a heart attack. Or been hit by a bus. Or overdosed on pills.

    The median age of diagnosis for HPV+ oropharyngeal cancers in one study was about 61 for both men and women, so this is not a young group. For this disease, depending on the source you use, that five-year survival rate is around 90%, which is really good for cancer. For pancreatic cancer, that number is closer to 5%. If you get checked out at that five year appointment and the doc finds NED (no evidence of disease), then you're a survivor. If you don't go back to the doc for the five year appointment, you are still a survivor, but your status (NED) is simply unclear because no one looked for evidence. Many doctors don't use the word "cured" anymore because they can't back that word up with any data that will guarantee that status. And as with everything in life, your mileage may vary because we are all unique individuals. Our genes are different, as are our immune systems and our lifetime exposure to toxic chemicals. So hang in there and hope for the best, and when you get there, enjoy your NED status. Life offers no guarantees, and the diagnosis is life changing, but you have to have hope going forward.