Let’s Talk About HPV-related Head and Neck Cancer: Now What? Calling the Dental Team to Action!

by Cecilia Dong, DMD, BSc (Dent), MSc (Prosthodontics), FRCD(C); Saranjeev Lalh, BSc, DDS, MD, FRCD(C); Lee Darichuk, BSc, DMD, MDent, FRCD(C); Peter Spafford, MD, FRCS(C); James Yacyshyn, BSc, DDS, MASc; Cheryl Cable, BSc, DDS, MBA, Prosthodontic and Maxillofacial Prosthodontics Cert., FRCD(C)

Gone are the days when only tobacco and alcohol were the main risk factors that needed to be discussed with dental patients during head and neck cancer screening examinations. A widespread change in how patients are educated on prevention of head and neck cancer is urgently needed because of a new and distinct type of head and neck cancer caused by a virus. There is an increasing incidence of infections with high-risk strains of Human Papillomavirus (HPV) leading to the development of head and neck cancer, especially oropharyngeal cancer.1-4 The costs associated with treatment and quality of life of these patients is staggering.5-16 The dental team is well-positioned to contribute to patient education for prevention, early detection, and management of head and neck cancer, but the topic of HPV-related head and neck cancer presents a unique challenge.17,18 HPV is a sexually transmitted disease, so it is a sensitive and potentially uncomfortable topic to discuss for both patients and the dental team. A patient may not understand how a sexually transmitted disease is relevant to conversations in a dental office. Members of the dental team may hesitate to initiate the conversation if they are lacking knowledge, comfort with the topic, and the environment does not have adequate privacy.20 The burden of head and neck cancer is high on the patient, caregivers, and society as a whole. HPV-related head and neck cancer is preventable with timely education and intervention.21-25 The dental team has a key opportunity to act as healthcare influencers in the prevention, detection, and treatment of HPV-related head and neck cancer.

Three clinical scenarios will be presented to highlight foundation knowledge on HPV-related head and neck cancer. Considerations and conversations with patients will vary depending on the age and profile of the patients.

CASE 1: MALE HPV-RELATED OROPHARYNGEAL CANCER PATIENT

This is a typical case of HPV-related oropharyngeal cancer. A 55-year-old male Caucasian investment banker presented with a large left neck mass located in the upper neck (level 2). An enlarging lump was first noticed several months ago, but this was ignored by the patient because he was generally feeling healthy, the throat pain was very mild, unilateral referred ear pain was moderate, and he occasionally tasted blood. He denied any symptoms of infection. He has never smoked and rarely drinks. He has a demanding work life that interfered with seeing his family physician sooner. It would have been preferable if this patient had seen his dentist before the cancer diagnosis, to be educated on symptoms of oral cancer – thereby eliminating the preventable delay in detection, diagnosis, and treatment.

There was a non-tender, partly fixed, rubbery, upper left side, neck mass measuring approximately 30-40 mm. A very subtle left palatine tonsillar mass approximately 5 mm diameter was also noted. The lesion was indurated and hard on palpation. Very scant bleeding from the lesion occurred when palpated. Dentists palpate the lymph nodes bilaterally in an oral cancer examination, so dentists have the ability to detect the large neck nodes that are often the first sign of oropharyngeal cancer. Oropharyngeal cancer is usually detected at an advanced stage because of the difficulty in visualizing changes in the soft tissues of the oropharynx, unless the lesion is clearly visible at the clinical examination. (Fig. 1) Fiberoptic nasopharyngolaryngoscopy allows better visualization of the base of the tongue, the inferior aspect of the tonsils, the hypopharynx and larynx. Ultrasound was used to evaluate the neck mass and surrounding lymph nodes. Other imaging along with blood work was part of the diagnostic process, but the key to diagnosis was a fine needle aspiration biopsy and HPV immunohistochemistry.

Fig. 1

 Visible tonsil mass in an oropharyngeal cancer patient which is in contrast to an almost normal looking throat in other oropharyngeal cancer patients (courtesy of Dr. Peter Spafford)
Visible tonsil mass in an oropharyngeal cancer patient which is in contrast to an almost normal looking throat in other oropharyngeal cancer patients (courtesy of Dr. Peter Spafford)

Biopsy results confirmed his diagnosis of HPV (p16+) oropharyngeal squamous cell carcinoma (Figs. 2-3) with unilateral upper neck metastases. Management is dependent on the clinical staging and clinical context and is best handled by a multidisciplinary team. Oral health should be restored and be optimal prior to beginning cancer treatment.

Fig. 2

. 40 x H&E (40 times original magnification with Hematoxylin and Eosin stain): Invasive epithelial nest and islands with tumor associated lymphocytic proliferation and muscle invasion (courtesy of Dr. Saranjeev Lalh and Dr. Pallavi Parshar).
40 x H&E (40 times original magnification with Hematoxylin and Eosin stain): Invasive
epithelial nest and islands with tumor associated lymphocytic proliferation and muscle invasion (courtesy of Dr. Saranjeev Lalh and Dr. Pallavi Parshar).

Fig. 3

40 x p16: Original magnification x 40 with p16 immunostaining is used as a surrogate marker for transcriptionally active HPV. High correlation with HPV infection in head and neck squamous cell carcinoma. (courtesy of Dr. Saranjeev Lalh and Dr. Pallavi Parashar).
40 x p16: Original magnification x 40 with p16 immunostaining is used as a surrogate marker for transcriptionally active HPV. High correlation with HPV infection in head and neck squamous cell carcinoma. (courtesy of Dr. Saranjeev Lalh and Dr. Pallavi Parashar).

HPV related oropharyngeal cancer is caused by the p16 and p18 high risk strains of HPV 85-90% of the time.2,4,5,6 In the past decade, there has been a rapid rise in HPV related oropharyngeal cancer in Canada and globally. The typical HPV related oropharyngeal cancer patient is middle-aged, more educated, and more affluent than the traditional (HPV negative) cases. They often lack a smoking and alcohol history and appear healthy. Table 1 lists major differences between HPV positive and HPV negative patient profiles.

Table 1: Oropharyngeal Squamous Cell Carcinoma Patient Profiles

The majority of HPV related oropharyngeal cancer patients are treated with chemo-radiotherapy. Robotic surgery tends to be used for smaller lesions. Fortunately, HPV positive oropharyngeal cancer is more responsive to treatment and generally has a better prognosis than HPV negative oropharyngeal cancer. Many clinical trials are ongoing to assess optimal treatment with best quality of life outcomes. If cancer treatment can be less aggressive for HPV positive oropharyngeal cancer patients, then side effects may be reduced, thus improving survivorship. As these are younger patients who were working at the time of diagnosis, an important aspect to maintaining quality of life would be maintaining the ability to continue working.

Conversations about HPV and head and neck cancer should ideally occur before a cancer diagnosis. By making a patient aware of risk factors and the HPV vaccine, it may be possible to prevent this specific type of cancer and the hardships of treatment associated with the cancer. By making the patient aware of symptoms and the importance of seeking care at the first signs and symptoms, it is hoped that this will lead to an earlier diagnosis.

CASE 2: FEMALE HPV-RELATED OROPHARYNGEAL CANCER PATIENT

This patient was referred to a maxillofacial prosthodontist for continued care by a general dentist as the case is complex. (Figs. 4-6) She was diagnosed with squamous cell carcinoma on the left base of the tongue. The biopsy was HPV positive. Surgical treatment of the lesion included removal of a salivary gland. She also went through a course of radiation therapy. She has severe xerostomia, eats only on the right side, and has a cast partial upper denture that could not be used due to friable tissues. Her oral health had deteriorated following her cancer diagnosis, resulting in generalized caries and large failing restorations. She was depressed and overwhelmed by how her life had changed post treatment and was contemplating initiating an end-of-life protocol.

Fig. 4

Fig. 5

 Maxillary arch (courtesy of Dr. Cheryl Cable).
Maxillary arch (courtesy of Dr. Cheryl Cable).

Fig. 6

. Mandibular arch and tongue (courtesy of Dr. Cheryl Cable).
Mandibular arch and tongue (courtesy of Dr. Cheryl Cable).

DENTAL TREATMENT OPTIONS ARE:

  1. No treatment. Extract teeth as they break down. Provide pain control.
  2. Complete removable dentures. Not a viable option due to severe xerostomia.
  3. Fixed dental implant-retained prostheses.

The first treatment option is underway with extractions due to pain and tooth breakdown. She was not able to maintain optimal oral hygiene due to pain. Long term discussions on hygiene and maintenance are important due to prosthesis design and access for hygiene tools. Manual dexterity impacts hygiene abilities and consequently long-term prognosis. Prosthetic design can be changed as patient abilities change. Ongoing communication with her medical team is necessary to ensure that the patient’s wishes are followed and that her quality-of-life concerns are addressed by qualified professionals in a timely fashion.

CASE 3: PREVENTION OF HPV-RELATED HEAD AND NECK CANCER

When a teenage patient presents to the dental office for an examination and hygiene appointment, this is an opportunity for the dentist and dental hygienist to ask, “have you received your HPV vaccine yet?” If not, the dentist can write a prescription for the HPV vaccine and the patient can be directed to a pharmacist who provides vaccinations. If there is privacy in the dental operatory, then further information on HPV can be provided and the nature of the sexually transmitted infection discussed. Focusing on this being an anti-cancer vaccine is a helpful approach to encourage acceptance, as well as emphasizing that vaccination can help reduce the risk that one could transmit the virus to someone else. One author in this paper describes vaccination as “protecting against cancers of the mouth, cancers of the throat, and cancers below the belt”.

Patients who have not been vaccinated for HPV should be provided educational material to decide on their personal risk factors. The National Advisory Committee on Immunizations does not list an upper age limit for receiving this vaccine. Any patient who is sexually active should be considered a candidate for vaccination.

CONCLUSION

The public is becoming more aware of HPV and head and neck cancer. Research by Habbous et al. made the local and national news in 2017 when it was published in the Canadian Medical Association Journal.8 Since patients often see dentists more than their family physicians, these dental appointments provide opportunities for patient education to increase awareness and discuss prevention as well as the potential for early detection of head and neck cancer. These conversations are only possible if dentists and team members are willing, comfortable, and knowledgeable to discuss HPV-related head and neck cancer. The development of patient education tools is critical to facilitate these education opportunities.22-28 Let’s continue to talk to our patients about HPV-related head and neck cancer.

A CALL TO ACTION BY THE CHIEF DENTAL OFFICER OF CANADA IS AS FOLLOWS:24

  • Stay up to date on evidence related to HPV infection and oral cancers.
  • Conduct mouth cancer screening at regular check-ups.
  • Recognize and detect signs and symptom at an early stage, and monitor any abnormal or suspicious lesion(s) in the mouth.
  • Explore the possibility of collecting samples at the dental office (by oral rinses or swabs) for HPV detection.
  • Explain to patients the links between oral HPV and oral cancer.
  • Share clear and evidence-based information and discuss with patients the known risk factors (such as tobacco use) and modes of transmission, including sexual practices and behaviours.
  • Continue to actively promote the importance of good oral hygiene and oral health as factors in prevention of HPV infection and HPV-related oral cancers.
  • Promote the HPV vaccine as a safe and effective way to prevent the infection.
  • Discuss with dentist regulatory bodies the possibility of administering the HPV vaccine in dental office (This authorization already exists in the Province of Alberta, with storage and reporting requirements).

Oral Health welcomes this original article.

References

  1. Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian Cancer Statistics 2016.
  2. National Cancer Institute, National Institute of Health. Head and Neck Cancers: https://www.cancer.gov/ types/head-and-neck/head-neck-fact-sheet#q1
  3. de Martel C, Plummer M, Vignat J, Franceschi S. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 2017 Aug 15;141(4):664-670. doi: 10.1002/ijc.30716. Epub 2017 Jun 8. PMID: 28369882; PMCID: PMC5520228.
  4. National Cancer Institute, National Institute of Health. Head and Neck Cancers: https://www.cancer.gov/ types/head-and-neck/head-neck-fact-sheet#q1
  5. Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma. J Clin Oncol. 2015 Oct 10;33(29):3235-42. doi: 10.1200/JCO.2015.61.6995. Epub 2015 Sep 8. PMID: 26351338; PMCID: PMC4979086.
  6. Senkomago V, Henley SJ, Thomas CC, Mix JM, Markowitz LE, Saraiya M. Human Papillomavirus-Attributable Cancers–United States, 2012-2016. MMWR Morb Mortal Wkly Rep. 2019 Aug 23;68(33):724-728. doi: 10.15585/mmwr.mm6833a3. PMID: 31437140; PMCID: PMC6705893.
  7. Van Dyne EA, Henley SJ, Saraiya M, Thomas CC, Markowitz LE, Benard VB. Trends in Human Papillomavirus-Associated Cancers– United States, 1999-2015. MMWR Morb Mortal Wkly Rep. 2018 Aug 24;67(33):918-924. doi: 10.15585/mmwr.mm6733a2. PMID: 30138307; PMCID: PMC6107321.
  8. Habbous S, Chu KP, Lau H, Schorr M, Belayneh M, Ha MN, Murray S, O’Sullivan B, Huang SH, Snow S, Parliament M, Hao D, Cheung WY, Xu W, Liu G. Human papillomavirus in oropharyngeal cancer in Canada: analysis of 5 comprehensive cancer centres using multiple imputation. CMAJ. 2017 Aug 14;189(32):E1030-E1040. doi: 10.1503/cmaj.161379. PMID28808115; PMCID: PMC5555753.
  9. Gillison ML, Broutian T, Pickard RK, Tong ZY, Xiao W, Kahle L, Graubard BI, Chaturvedi AK. Prevalence of oral HPV infection in the United States, 2009-2010. JAMA. 2012 Feb 15;307(7):693-703. doi: 10.1001/jama.2012.101. Epub 2012 Jan 26. PMID: 22282321; PMCID: PMC5790188.
  10. CDC. 2018 HPV & Cancer. How Many Cancers are Linked to HPV Each Year? https://www.cdc.gov/cancer/hpv/statistics/cases.htm
  11. Saraiya M, Unger ER, Thompson TD, Lynch CF, Hernandez BY, Lyu CW, Steinau M, Watson M, Wilkinson EJ, Hopenhayn C, Copeland G, Cozen W, Peters ES, Huang Y, Saber MS, Altekruse S, Goodman MT; HPV Typing of Cancers Workgroup. US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines. J Natl Cancer Inst. 2015 Apr 29;107(6):djv086. doi: 10.1093/jnci/djv086. PMID: 25925419; PMCID: PMC4838063.
  12. Chesson HW, Meites E, Ekwueme DU, Saraiya M, Markowitz LE. Updated medical care cost estimates for HPV-associated cancers: implications for cost-effectiveness analyses of HPV vaccination in the United States. Hum Vaccin Immunother. 2019;15(7-8):1942-1948. doi: 10.1080/21645515.2019.1603562. Epub 2019 May 20. PMID: 31107640; PMCID: PMC6746487.
  13. Righolt CH, Pabla G, Mahmud SM. The Direct Medical Costs of Diseases Associated with Human Papillomavirus Infection in Manitoba, Canada. Appl Health Econ Health Policy. 2018 Apr;16(2):195-205. doi: 10.1007/ s40258-017-0367-1. PMID: 29299769.
  14. Osazuwa-Peters N, Simpson MC, Zhao L, Boakye EA, Olomukoro SI, Deshields T, Loux TM, Varvares MA, Schootman M. Suicide risk among cancer survivors: Head and neck versus other cancers. Cancer. 2018 Oct 15;124(20):4072-4079. doi: 10.1002/ cncr.31675. Epub 2018 Oct 18. PMID: 30335190.
  15. Aldossri M, Okoronkwo C, Dodd V, Manson H, Singhal S. Dentists’ Capacity to Mitigate the Burden of Oral Cancers in Ontario, Canada. J Can Dent Assoc. 2020 Feb;86:k2. PMID: 32119642
  16. Ellington TD, Henley SJ, Senkomago V, O’Neil ME, Wilson RJ, Singh S, Thomas CC, Wu M, Richardson LC. Trends in Incidence of Cancers of the Oral Cavity and Pharynx–United States 2007-2016. MMWR Morb Mortal Wkly Rep. 2020 Apr 17;69(15):433-438. doi: 10.15585/mmwr.mm6915a1. PMID: 32298244; PMCID: PMC7755056.
  17. Clarke AK, Kobagi N, Yoon MN. Oral cancer screening practices of Canadian dental hygienists. Int J Dent Hyg. 2018 May;16(2):e38-e45. doi: 10.1111/idh.12295. Epub 2017 Jun 23. PMID: 28643363.
  18. Chaturvedi AK, Graubard BI, Broutian T, Xiao W, Pickard RKL, Kahle L, Gillison ML. Prevalence of Oral HPV Infection in Unvaccinated Men and Women in the United States, 2009-2016. JAMA. 2019 Sep 10;322(10):977-979. doi: 10.1001/jama.2019.10508. Erratum in: JAMA. 2019 Nov 19;322(19):1925. Erratum in: JAMA. 2020 Jan 21;323(3):282. PMID: 31503300; PMCID: PMC6737522.
  19. Chaturvedi AK, Graubard BI, Broutian T, Pickard RKL, Tong ZY,Xiao W, Kahle L, Gillison ML. Effect of Prophylactic Human Papillomavirus (HPV) Vaccination on Oral HPV Infections Among Young Adults in the United States. J Clin Oncol. 2018 Jan 20;36(3):262-267. doi: 10.1200/JCO.2017.75.0141. Epub 2017 Nov 28. PMID: 29182497; PMCID: PMC5773841.
  20. O’Connor M, Waller J, Gallagher P, O’Donovan B, Clarke N, Keogh I, MacCarthy D, O’Sullivan E, Timon C, Martin C, O’Leary J, Sharp L. Barriers and facilitators to discussing HPV with head and neck cancer patients: A qualitative study using the theoretical domains framework. Patient Educ Couns. 2020 May 30:S0738-3991(20)30318-9. doi: 10.1016/j.pec.2020.05.032. Epub ahead of print. PMID: 32565003.
  21. https://clinicaltrials.gov/ct2/show/NCT04199689;
  22. WHO Primary end-points for prophylactic HPV vaccine trials. International Agency for Research on Cancer (IARC) Working Group Report 2014
  23. https://www.fda.gov/vaccines-blood-biologics/vaccines/gardasil-9
  24. https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2020-46/issue11-12-november-5-2020/human-papillomavirus-oral-health.html
  25. https://www.entcanada.org/cso/position-statements/position-statement-hpv-vaccination-for-males/
  26. https://www.dentalhealthalberta.ca/preventing-hpv-positive-oropharyngeal-cancer/
  27. https://www.ada.org/en/publications/ada-news/2018-archive/october/ada-adopts-policy-supporting-hpv-vaccine
  28. https://hpvroundtable.org/action-guides/

About the Authors

Dr. Dong is an Assistant Professor in the Division of Prosthodontics, Schulich School of Medicine and Dentistry at Western University. She is cross-appointed to Pathology and Laboratory Medicine, and Otolaryngology – Head & Neck Surgery.

 

 

Dr. Lalh completed his General Surgery and Oral and Maxillofacial Surgery training in Pittsburgh and has been a Clinical Professor at the University of Alberta for 20+ years. He is Section Head at the Royal Alexandra Hospital.

 

 

Dr. Darichuk is an Oral & Maxillofacial Surgeon in Calgary and serves on the council of the Alberta Dental Association & College.

 

 

 

Dr. Spafford received his MD degree from the University of Saskatchewan and did his residency in Otolaryngology in Vancouver.

 

 

Dr. Yacyshyn teaches Practice Management at the University of Alberta and owns and operates a multidisciplinary private practice. He is the Division Head of Continuing Dental Ed. at the University of Alberta.

 

 

Dr. Cable is an Associate Professor at the Faculty of Medicine and Dentistry at the University of Alberta. She is the Lead of the Alberta Head & Neck Cancer Dental Leadership Team

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