HPV: Changing the Face of Head & Neck Cancer

HPV is Changing the Face of Head and Neck Cancer:

An Emerging Epidemic!

by Karen Sheffler, MS, CCC-SLP, BCS-S of SwallowStudy.com (revised April 25, 2017)

Young people who do not smoke do NOT get cancer, right?
Wrong.
We need to have the talk — about sex and the Human Papilloma Virus (HPV).

HPV is changing everything Speech-Language Pathologists (SLP) and the medical community know about cancer of the mouth and throat (oropharyngeal cancer).

A changing demographic: (Gillison, et al, 2008; Westra, 2009)

• Younger, with mean age of 59 for men and 62 for women per the CDC’s 2008-2012 statistics. (However, the CDC found it peaked in two age groups: 30-34 and 60-64 year olds)
• White male (Ratio of men to women is 3:1, as women may make antibodies in the cervix after early exposure.)
• Married
• College educated
• Average income of >$50,000
• We cannot blame smoking, alcohol, poor oral hygiene, or age for this cancer as we could with head and neck cancer not related to HPV (aka HPV-negative).

As people smoke less, the incidence of HPV-negative cancer is going down. Per the National Cancer Institute’s (NCI) Annual Report to the Nation on the Status of Cancer, published in 2017, the incidence of cancer has decreased, particularly for men with the following cancer locations: prostate, colon, rectum, lung, larynx, brain, bladder and esophagus.  However, oropharyngeal cancers are on the rise per this NCI report. For women, while cervical cancer is declining, the incidence of oral cancer has increased. At the ASHA 2014 Health Care & Business Institute, Katherine Hutcheson, PhD, CCC-SLP, BCS-S, of MD Anderson Cancer Center, stated that 70% of new oropharyngeal cancers are HPV-positive. More recently, at the 2016 Annual Meeting of the Dysphagia Research Society, Jonas Johnson, FACS noted 80-90% of new oropharyngeal cancers are HPV-positive (Johnson, 2016, February).

HPV is most often a sexually transmitted infection. HPV-positive DNA of the HPV-16 (same type as in cervical cancer) was initially discovered in an oral carcinoma in 1985. However, HPV-positive oropharyngeal cancers increased 225% between 1988 and 2004, especially in white males (Chaturvedi, 2011). It is thought to be passed from girls to boys. HPV-11 only causes warts, but now HPV-16-18 account for 95% of the oropharyngeal cancer (Johnson, 2016, February). By the age of 25, 85-90% of people have been infected with HPV, but have cleared it. From the first exposure to oropharyngeal cancer can be as much as 30 years, for the unfortunate few who did not make antibodies against the virus (Johnson, 2016, February).

The incidence rate of HPV-positive tumors is on course to double each decade, making it an epidemic of virus-induced carcinoma.

More education is critically needed to stem the rising tide of HPV-positive infections.

Please see the CDC’s page on HPV for the most up-to-date information, for example:

“CDC now recommends 11 to 12 year olds get two doses of HPV vaccine—rather than the previously recommended three doses—to protect against cancers caused by HPV. The second dose should be given 6-12 months after the first dose. For more information on the updated recommendations, read the MMWR: https://www.cdc.gov/mmwr/volumes/65/wr/mm6549a5.htm.”

Risk factors for HPV-positive oropharyngeal cancer (Gillison, et al, 2008; Westra, 2009):

• Increased number of sexual partners

• Participation in “casual sex”

• Infrequent use of barrier protection during all sexual contact

• Oral-genital contact and oral-anal contact

• History of sexually transmitted diseases

• Prolonged and frequent marijuana use (per Gillison, et al, 2008). Authors speculated that cannabinoids bind with receptors expressed on natural killer cells, including T cells present in human tonsillar tissue. This may inhibit anti-tumor immunity. Cannabinoids may also reduce the host’s resistance to viral pathogens and immune response. Then the host has an increased risk for infection and persistent infection.

• Note: both tobacco and alcohol were NOT associated with HPV-positive oropharyngeal cancer, but they are strongly associated with HPV-negative oropharyngeal cancer. Very heavy tobacco smoking trended towards increasing the HPV-positive odds, but it did not reach statistical significance (Gillison, et al, 2008).

Persistent infections:

The CDC states that 85% of all adults may have an HPV infection once in their lifetime. Not everyone infected with HPV will get cancer. There are many strains of HPV, but only a few of them are known to cause cancer. The most common one is HPV-type 16. A viral infection could start in a micro-injury in the mouth, but the majority of infections are rapidly cleared by the body’s immune system (Wittekindt, et al, 2012). However, it is the persistence of a HPV-induced lesion that may cause it to progress. Then the process from infection to carcinoma is also a slow one. It can take over 10 years for the persistent infection to transform the infected host cells. As the viral DNA integrates into the host cells, it can progress to a dysplasia and then a carcinoma (Wittekindt, et al 2012). Once it turns into an oncogenic virus, it is no longer transferrable. The most common sites for this are in the “tonsillar crypts” of the lingual and palatine tonsils (Westra, 2009). It is often difficult to see an HPV-positive lesion, so people should pay attention to symptoms that persist.

Symptoms: (per A Voice for Hope: www.mouthandthroatcancer.org)

1. Sores in the mouth that do not heal in 2-3 weeks

   

   White and red surface alterations that were found to be squamous cell carcinoma. The key is to catch lesions in a pre-cancerous stage. Image: www.emedicine.medscape.com/article/1840467-overview

2. Red or white patches in the mouth

3. Bleeding-non-healing ulcers
   

4. Lump or swelling in the neck or under the chin (a non-painful lump in the neck has been found in 51% of HPV-positive cancers, per Miller, 2016)

5. Difficulty swallowing (dysphagia) and pain with swallowing

6. Ongoing earache (pain radiating to ear)

7. Hoarseness that lasts for more than 2-3 weeks (if lesion is at the level of the vocal folds, but less common with HPV)

Changing survival rates:

This is the good news!

The likelihood of survival at 3 years after treatment from HPV-positive cancer is 93% (Johnson, 2016, February; Lin, et al, 2013 – Johns Hopkins study). This is far better than 46% for HPV-negative head and neck cancers, due to smoking and alcohol use. However, if you are a smoker and have an HPV-positive cancer, your 3-year likelihood of survival drops to 71% (Johnson, 2016, February).

Five-year survival rates are in the 80 percent ranges, depending on the stage of your cancer. The survival rate only drops to 60% at 5 years with deeply invasive and large tumors with extensive lymph node involvement (i.e., Stage IVB), per O’Sullivan, et al., 2016.

Imagine if you are treating a 40-year-old male with oropharyngeal cancer, and his swallowing is drastically affected by a full course of chemotherapy and radiation. He will live another 50+ years with these deficits. Additionally, the young man’s identity, relationships and future productivity are at risk. We need to catch these people early on for the best outcomes. HPV-positive cancer is very sensitive to radiation; therefore, research is being done to “de-escalate” or reduce the degree of radiation (more on this below).

Fortunately, we have star-power to help educate:

Michael Douglas addressed the American Head & Neck Society and the International Federation of Head & Neck Oncology Society on July 27, 2014. (This date is now the World Head & Neck Cancer Day).

When Douglas stated how he owed his life to the team at the Memorial Sloane Kettering Cancer Center, I realized that many young people will now owe their lives to Michael Douglas. He is raising awareness of this urgent public health issue. Physicians and healthcare professionals who evaluate the mouth (i.e., SLP and dentist) need to have HPV in their radar when a patient comes in with suspicious symptoms. Do not think: “Well, he is not an old guy who smokes with cancer history.”

Michael Douglas painfully described how he had been misdiagnosed three times in the summer of 2010. His symptoms started with a sore spot in his gums behind his last molar and a vague sore throat. (Some people also feel pain with swallowing or pain radiating up to an ear). After seeing a primary care physician, an ENT, and then a periodontist, he was finally diagnosed with HPV-positive oropharyngeal cancer by an ENT at McGill University in Montreal. After months of delay, the tumor size was large (Stage IV). Survival is directly related to the extent of the cancer progression and the stage of cancer at diagnosis (Westra, 2009).

Keys to surviving and thriving, per Michael Douglas:

1. Realize that you are in for “7 cycles of hell” with radiation and chemotherapy.

2. Expect to feel awful. Douglas recalled how he sank lower each week.

3. Prepare for battle like a soldier.

4. Maintain a sense of control. You are part of the team.

5. Work with the team. He stated: their job is to treat you and your job is to toughen up.

6. “Cancer cannot be fought as a series of individual battles, but as a well-planned war, in which all of us…are allies.”

Michael Douglas stated: “I’m living proof of the progress this field is making.”

After waging his war, refusing a feeding tube, struggling to maintain nutrition with liquids, losing 40 pounds, he is alive and thriving. He is urging the medical field to stay up-to-date and in-sync. Cooperation across nations will push the field farther, improving quality and effectiveness of treatments. Education and sharing knowledge is critical so that misdiagnosis does not continue. Douglas hopes the latest advances will reach every corner of the field and world.

HPV may change how we treat cancer:

The future does look brighter.

Conventional treatment for head and neck cancer causes a lot of collateral damage to the healthy tissue. The combination of chemoradiotherapy (CRT) has been found to cause significant early and late effects on voice and swallowing. Years and decades later a patient will still suffer from dysphagia due to increasingly fibrotic-stiff muscles, dry mouth, de-nervation, decreased sensation, and more. Now there is research into these HPV-positive cancers to try to decrease the toxicity of treatment in this lower-risk, non-smoking population whose tumors respond better to radiation than HPV-negative tumors. Better diagnostic imaging, dose sculpting, individualized tumor therapy, proton therapy, and less-aggressive molecular targeted therapies all give hope. Even with IMRT, low doses of radiation splash around to healthy tissue. Radiation oncologists are trying to reduce the amount of absorbed radiation dose (i.e., <50 Gray), especially to spare at least one parotid gland and avoid the superior pharyngeal constrictors when possible. Overall, there is hope that de-escalation or de-intensifying chemoradiotherapy can provide good results with less side effects.

For more information on ongoing de-escalation trials, see the 2016 article in the reference section below from Naghavi and colleagues titled: Management of oropharyngeal cancer in the HPV era.

Referrals need to be made earlier to the SLP swallowing specialist. The SLP can start educating patients pre-radiation, and continue to work with patients through radiation. We customize exercise programs for the patient to continue throughout all treatment. We can advocate for the patients as they experience issues such as appetite decline, weight loss, mucositis, pain, depression, and more – working with a multidisciplinary team and making appropriate referrals. When therapy programs include: avoiding NPO (nothing-by-mouth) status, continuing to swallow, maintaining some physical exercise, and stressing oral hygiene, the patients do better than programs addressing aspiration issues alone.

Prevention is the Key:

There is no screen yet for HPV. The key is to vaccinate before exposure, especially in boys from 11 to 21, but also for girls from 11-26 years of age. Dr Jonas Johnson, FACS, Otolaryngologist from the University of Pittsburgh was disappointed by the slow acceptance of vaccination, but did note that the American College of Pediatrics is on now board with vaccinating youth prior to exposure. He noted that 66 million doses have been given so far without any serious side-effects. Johnson also noted that the vaccines are covered by the Affordable Care Act, and there is no evidence that vaccinating youth promotes risky behavior.

Again, please see the CDC’s page on HPV for the most up-to-date information, for example:

“CDC now recommends 11 to 12 year olds get two doses of HPV vaccine—rather than the previously recommended three doses—to protect against cancers caused by HPV. The second dose should be given 6-12 months after the first dose. For more information on the updated recommendations, read the MMWR: https://www.cdc.gov/mmwr/volumes/65/wr/mm6549a5.htm.”

Summary:

There are enough differences between HPV-positive cancers and HPV-negative cancers that we need to consider these two distinct head and neck cancers. All healthcare professionals can play a role in raising awareness of HPV-related oropharyngeal cancers.

We have come a long way just since 2012.

In 2012, the American Head and Neck Society’s position statement on cancer of the head and neck did not consider HPV-positive cancers when it summarized: “Those patients at risk for this disease are well characterized, with the clearest risk factors for the development of these malignancies, being a history of tobacco and alcohol use.” (AHNS, 2012, paragraph 1).

This did not reflect the changing demographic and reflected the need for ongoing education.

Due to the “emerging epidemic” of HPV-associated oropharyngeal cancers, AHNS released this statement in 2014: “The AHNS advocates for the performance of a comprehensive oral and head and neck exam, particularly in symptomatic or at risk individuals as the best known method of detecting oral and oropharyngeal cancers.” (quotes from AHNS, 2014, paragraphs 4 and 3, respectfully. See full statement in link under References).

Then in 2015, the AHNS, along with the American Academy of Otolaryngology – Head and Neck Surgery, published position statements specifically regarding vaccination and prevention of HPV-related oropharyngeal cancer.

Prevention is also in our scope of practice as SLPs (See Hapner’s article, 2012). Continuing education will help us keep HPV-positive oropharyngeal cancer in our radar when we are evaluating a person’s oral cavity, voice and swallowing. We need to be at the forefront in early detection, as well as in preventing some of the toxicity and dysphagia caused by chemoradiotherapy.

Call to Action: What can the SLP do?

We do not diagnose cancer, but we can screen and make appropriate referrals.

Follow this simple 8-step screening tool

(adapted from A Voice for Hope: www.mouthandthroatcancer.org)

1. Neck: feel for areas of tenderness or lumps on both sides of neck and under the lower jaw.

2. Lips: with gloved fingers, pull out each lip and look for sores or color changes inside the lips. Feel for lumps within lip tissue.

3. Cheeks: with gloved fingers, pull out the cheek and look inside at the tissue for sores or color changes. Use thumb and index finger to feel for lumps in cheek tissue.

4. Gums: with gloved fingers, pull open the lips to visualize the gum line. Look for discoloration or sores on the gums all around the teeth.

5. 

   SLP needs to let the physician know when noting any white or red patches in oral exam.

   Tongue: use gloved fingers and gauze/cloth to hold the end of the tongue. Pull the tongue side to side. Have patient stick it out and then curl it up as far as he can. Look at surface and under the tongue for color changes, sores, or bumps.

6. Palate: look at hard and soft palate for tissue color changes, sores, or bumps.

7. Voice: listen for hoarseness or harshness in vocal quality. Listen for changes in nasality.

8. Swallowing: ask about any difficulties swallowing food, liquids, or pills. Ask about pain with swallowing and if the pain radiates anywhere (i.e., up to ear).

Resources:

• Voices for Hope: United Against Mouth and Throat Cancer at www.mouthandthroatcancer.org 

• Oral Cancer Foundation at www.oralcancerfoundation.org

• American Academy of Otolaryngology at www.entnet.org/healthinformation

• National Foundation of Swallowing Disorders (NFOSD) at www.swallowingdisorderfoundation.org

References:

American Head and Neck Society. (2012). Position statement on screening for head and neck cancer. Retrieved from: https://www.ahns.info/documents/FinalScreeningPositionStatementPreventionCommitteFIN..pdf

American Head and Neck Society. (August 5, 2014). AHNS Response to USPSTF recommendation for screening of oral and oropharyngeal cancer. Retrieved from: https://www.ahns.info/ahns-recommendation/

Beckley, E. (2013). Casualties of intimacy: As an epidemic of HPV-related oropharyngeal cancer takes hold, SLPs are uniquely positioned to help affected patients navigate the grueling treatments. The ASHA Leader, 18, 38-43. doi:10.1044/leader.FTR1.18102013.38

Chaturvedi, A. K., Engels, E. A., Pfeiffer, R. M., Hernandez, B. Y., Xiao, W., Kim, E., … Gillison, M. L. (2011). Human papilloma virus and rising oropharyngeal cancer incidence in the United States. Journal of Clinical Oncology, 29(32), 4294–4301.

Gillison M.L., D’Souza G., Westra W., Sugar E., Xiao W., Begum S. & Viscidi R. (2008). Distinct risk factor profiles for human papilloma virus type 16-positive and human papilloma virus type 16-negative head and neck cancers. Journal of the National Cancer Institute, 100 (6), 407-20. doi: 10.1093/jnci/djn025

Hapner, E.R. (2012). The Speech-Language Pathologist’s role in screening for head and neck cancer. SIG 3: Perspectives on Voice and Voice Disorders, 22, 6-13. doi:10.1044/vvd22.1.6

Johnson, J. (2016, February). Oropharyngeal Cancer in the Era of HPV. Session presented at the Post-Graduate Course: Something You Can Chew On: Evidence-based Dysphagia Clinical Care at the Dysphagia Research Society 2016 Annual Meeting, Tucson, AZ.

Lin, B. M., Wang, H., D’Souza, G., Zhang, Z., Fakhry, C., Joseph, A. W., … Pai, S. I. (2013). Long term prognosis and risk factors among HPV-associated oropharyngeal squamous cell carcinoma patients. Cancer, 119(19), 3462–3471. https://doi.org/10.1002/cncr.28250

Miller, R.J. (2016). HPV Virus Infections and Oropharyngeal Cancer. Presentation downloaded on April 25, 2017 from www.slideshare.net/doctorbobm/HPV-Virus-infections-and-oropharynx-cancer/.

Naghavi, A.O., et al. (2016). Management of oropharyngeal cancer in the HPV era. Cancer Control: A Journal of the Moffitt Cancer Center, 23 (3), 197-207. Read pdf.

O’Sullivan, B. et al. (2016). Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): A multicentre cohort study. The Lancet Oncology, 17 (4), 440-451.

Westra, W.H. (2009). The Changing face of head and neck cancer in the 21st Century: The impact of HPV on the epidemiology and pathology of oral cancer. Head and Neck Pathology, 3, 78–81. DOI 10.1007/s12105-009-0100-y

Wittenkindt, C., Wagner, S., Mayer, C.S & Klussmann, J.P. (2012). Basics of tumor development and importance of human papilloma virus (HPV) for head and neck cancer. GMS Current Topics in Otorhinolaryngology – Head and Neck Surgery, 11, 1-29. ISSN 1865-1011