OROPHARYNX CANCER. Anthony Zeitouni, MD, FRCSC. Co-Lead, Head Neck Cancer Rossy Cancer Network

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1 OROPHARYNX CANCER Anthony Zeitouni, MD, FRCSC Co-Lead, Head Neck Cancer Rossy Cancer Network

2 CFPC CoI Templates: Slide 1 FACULTY/PRESENTER DISCLOSURE Faculty: Dr Anthony Zeitouni Relationships with commercial interests: nil

3 Introduction Outline Demographics Pathophysiology Diagnosis Staging Treatment Surgical Radiation Chemo Pycho-oncological Survivorship issues OUTLINE

4 HEAD AND NECK CANCER 6.5% of annual cancer cases worldwide 2/3 men 1/3 women 5000 new cases in Canada per year

5 HEAD AND NECK SURGERY Squamous cell cancer of the upper aerodigestive region Parotid and salivary gland cancers Skin cancers Thyroid cancers Sino-nasal cancers Skull Base tumors

6 Squamous cell cancers SQUAMOUS CELL CANCER OF THE UPPER AERODIGESTIVE SPHERE Change a persons ability to interact in society Speaking Eating Swallowing Appearance

7 Guo T, et al. Cancer INTRODUCTION The incidence of head and neck squamous cell carcinoma (HNSCC), an entity historically caused by tobacco and alcohol exposure, has decreased over the past 30 years. However, the incidence of oropharyngeal cancer (OPC), a subset of HNSCC, has risen significantly. This dramatic increase in OPC is driven by human papillomavirus (HPV) infection. Approximately 70% to 90% of newly diagnosed cases of OPC in the United States are caused by HPV. These HPV related cancers are often diagnosed in younger, healthier patients, many of whom are nonsmokers.

8 HEAD AND NECK SQUAMOUS CELL CANCER Oral Cavity Oropharynx Larynx Nasopharyx

9 OROPHARYNGEAL SITES The oropharynx begins where the oral cavity stops. Base of tongue (the back third of the tongue), soft palate, tonsils and tonsillar pillars, the back wall of the throat.

10 OROPHARYNX

11 Head and Neck Cancer Risk Factors HPV

12 TWO DISTINCT DISEASES HPV POSITIVE HPV NEGATIVE Histology Basaloid Keratinized Age Younger Older Gender 3:1 men 3:1 men SE status High low Risk Factors Sexual Behaviour ETOH, Tobacco Cofactors Marijuana, imunsupp ETOH, Tobacco Incidence Rising falling Survival Better worse 12

13 Overall survival according to HPV status Thibaudeau et al. Int J Otolaryngol, 2013

14 DEMOGRAPHICS

15 From 1988 to 2004, population-level incidence of: HPV-positive oropharyngeal cancers increased by 225% (95% CI ) HPV-negative cancers declined by 50% (95% CI 47-53)

16 OROPHARYNGEAL AND ORAL CAVITY CANCERS Oral cancers In Ontario men: Rates unrelated to HPV have been declining for over two decades 6.5 per 100,000 in 1981 to 5.1 in Rates of HPV-related oral cancers have been on the rise since per 100,000 in 1997 to 5.2 in The largest increase was observed in men age 55 to 64 Ontario Cancer Facts Jul 2011

Incidence of HPV-associated cancers 3760 cases were diagnosed in 2012 (64%

diagnosed, followed by anal and vulvar cancers Proportion (%) of new cases

Canadian Cancer Statistics 2016 Analysis by: Health Statistics Division,

17 Incidence of HPV-associated cancers 3760 cases were diagnosed in 2012 (64% in females ; 36% in males) OPC and cervical cancers were the most commonly diagnosed, followed by anal and vulvar cancers Proportion (%) of new cases for selected HPV-associated cancers, Canada 2012* *Quebec data are from 2010 Canadian Cancer Statistics 2016 Analysis by: Health Statistics Division, Statistics Canada Data source: Canadian Cancer Registry database at Statistics Canada

18 18 SEXUALLY TRANSMITTED Prevalence is < 0.3 % for those with no sexual hx For US population prevalence is 6.5% HPV is a common infection with a high prevalence in the population Infection occur via oral sex Infections usually resolve Very rarely lead to cancer Cancer develops over many decades Does not imply infidelity by patient or spouse

19 19

20 20 WHY IS PREVALENCE HIGHER IN MEN? Higher number of partners Only explains part of the difference in prevalence Per partner risk is 3-4 times higher in men than women Chaturvedi et al: data consistent with higher transmission when oral sex performed on a woman by a man Differences in immune response between genders Chaturvedi et al Cancer Res Ap 2015

21 Guo T, et al. Cancer ORAL HPV INFECTION RISK FACTORS Male gender: Lower antibody response to HPV in men or, Higher transmissibility of infection through oral sex performed on a women Age with bimodal distribution

22 Guo T, et al. Cancer ORAL HPV INFECTION RISK FACTORS Others: Smoking: 2 to 3 times higher in current smokers, with a significant dose-response realtionship Heavy alcohol use Sexual behaviors: Dose-response relationship between increasing numbers of lifetime sexual partners (oral and vaginal) and oral HPV infection Immunosuppression (HIV) Single status Deep kissing

23 PATHOPHYSIOLOGY

24 24 WHAT IS THE HUMAN PAPILLOMA VIRUS HPV is a sexually transmitted infection Many types of HPV Common in Canada, over 2 million have genital or oral HPV Rarely but in some people HPV can lead to tonsil cancer

25 HPV non-enveloped double stranded DNA virus L1 & L2 surface proteins >130 types low & high risk types species specificity

26 Human Papillomavirus Types and Disease Association mucosal/genital~40 types nonmucosal/cutaneous (~60 types) high-risk types 16, 18, 31, 45 (and others) low-risk types 6, 11 (and others) skin warts (hands and feet) low grade cervical abnormalities cancer precursors anogenital cancers HN cancers low grade cervical abnormalities genital warts laryngeal papillomas

27 BIOLOGY OF HPV INFECTION A single type, HPV 16, causes more than 90% of HPV-positive oropharynx cancer (Gillison, 2000) HPV proteins, E6 and E7 are the key drivers of carcinogenesis in oropharynx cancer by eliminating two of the most important tumor suppressors, p53 and Rb (Zur Haunsen, 2000; Zur Haunsen 2002; Chung, CH, 2009; Howard JD, 2012) Chung CH, et al Oral Oncology 2013

29 Guo T, et al. Cancer ORAL HPV INFECTION: NATURAL HISTORY Clearance of infection: within 6 to 12 months 80% of individuals clear the oral HPV infection by 1 year, regardless of HPV type Some infections persist for unknown reasons Risk factors for HPV persistence: male sex, older age, and current smoking status Other possible risk factors: high oral HPV viral load concurrent persistent cervical infection

30 DIAGNOSES Oropharynx cancer presentation different HPV vs HPV+ HPV Present most often with a sore throat x months HPV + Present with a neck node or persistent sore throat Unilateral painful tonsil

32 DIAGNOSIS High index of suspicion Individuals at risk Good physical exam Good light source Gloves and palpate Palpate tonsils Palpate base of tongue Palpate neck Non-tender neck nodes are always suspicious

33 TONSIL EXAM SUPPLIES

37 DIAGNOSIS: NECK NODES

38 If suspect cancer: CT Neck Look for large, often cystic neck nodes Asymmetrical tonsils Asymmetry base of tongue CXR, CT chest MRI PET Biopsy Mass in oropharynx Ultrasound guided neck node bx DIAGNOSIS

39 TREATMENT Surgical Radiation Chemo Pycho-oncological

40 TREATMENT OPTIONS DEPEND ON TNM STAGE

41 Overall survival according to HPV status Thibaudeau et al. Int J Otolaryngol, 2013

42 TREATMENT Eradicate cancer Minimize morbidity 85% or better 5 yr survival De-escalate treatment Minimize the number of modalities

43 TREATMENT In Open surgical approaches Followed by radiation Effective but surgery led to significant morbidity

44 TREATMENT In the last decade Chemo-radiation High dose of radiation with chemotherapy to augment the effect of xrt Worked well in eradicating disease High morbidly % of patients could not swallow after PEG dependence Dry mouth, dental disease

45 CHEMO-RADIATION 5-6 week of radiation Augmented by chemo using cis-platinum or carbo-platinum Effective >85% 5 year survival High rate of complications during treatment and in the years after Patients are young, and 85% survive their cancer Decades with the morbidity of treatment

46 ROBOTICS

47 ROBOTIC SURGERY Transoral resection 5 yr local control >90% 14% temporary trach 4% permanent G tube

48 COMPLICATIONS Psycho-social Physical

49 49 IMPACT OF HPV-POSITIVE STATUS ON PATIENTS WITH OPC AND THE NEED FOR COUNSELING The psychosocial burden of an HPV diagnosis has been well documented among women. Limited study measuring the impact of HPV-positive status of patients with OPC. Patients within these populations all share the same risk factors. It is necessary to extrapolate from the wealth of available data on women with HPV-induced cellular lesions Chu, A. The Oncologist 2013.

50 Respondants (%) PSYCHOSOCIAL REACTION TO DIAGNOSIS OF HPV At diagnosis Last 12 months Anger Depression Isolation Fear of rejection Shame Guilt n = 454 Clarke P, et al. Int J STD AIDS 1996; 7: Anhang R, et al. CA Cancer J Clin 2004; 54:

51 FREQUENTLY ASKED QUESTIONS REGARDING HPV POSITIVE OROPHARYNGEAL CANCER Topic Question Answer Duration of infection and progression to cancer Will I always have HPV? A healthy immune system suppresses the virus in most infected people. Experts are still determining whether HPV remains in the body, when HPV is no longer contagious, and how long it takes between HPV infection and development of oropharyngeal cancer. Chu, A The oncologist 2013

52 FREQUENTLY ASKED QUESTIONS REGARDING HPV POSITIVE OROPHARYNGEAL CANCER Topic Question Answer Transmission How, when, or from whom did I get HPV? HPV is a sexually transmitted virus. Most sexually active people will get HPV in their lifetimes. It is impossible to know with certainty from whom or when you acquired HPV because most people do not know they have it. Chu, A The oncologist 2013

53 FREQUENTLY ASKED QUESTIONS REGARDING HPV POSITIVE OROPHARYNGEAL CANCER Topic Question Answer Screening Can you do a pap smear of my tonsils There is currently no method for detecting the cancer in a precancerous stage, such as with the Pap test in cervical cancer. Chu, A The oncologist 2013

54 FREQUENTLY ASKED QUESTIONS REGARDING HPV POSITIVE OROPHARYNGEAL CANCER Topic Question Answer Prevention How can I avoid transmitting HPV to others? Lifetime mutual monogamy or abstinence are the best ways to prevent transmission. Condom use and fewer sexual partners are considered the mainstay of prevention. Experts are still determining what risks, if any, sexual partners of patients with HPVOPC have in developing cancer. Chu, A The oncologist 2013

55 FREQUENTLY ASKED QUESTIONS REGARDING HPV POSITIVE OROPHARYNGEAL CANCER Topic Question Answer Information for partners What should I tell my partner about my HPV status? Most infected people control HPV and do not develop signs or symptoms. If you decide to tell your partner about your HPV testing result, it is best to talk openly and honestly. Partners who have been together often share HPV, but it is impossible to know the direction of transmission. HPV is a common virus. It does not imply infidelity or promiscuity. There should be no shame or blame associated with an HPV diagnosis. Chu, A The oncologist 2013

56 ADDITIONAL RESOURCES Framework to clinicians to address frequently ask questions Fakhry, et al Oral Oncology 2013

57 Fakhry, et al Oral Oncology 2013

58 COMPLICATIONS: PHYSICAL Surveillance Recurrence Second primaries Mucosal XRT leads to loss of salivary function Dental problems Xerostomia Dysphagia and scarring Trismus: Endocrine: loss of thyroid function

59 PREVENTION

60 DISTRIBUTION OF TYPE-SPECIFIC HPV INFECTIONS FOUND IN OPC HPV-16: Most common high-risk infection Approx. 90% of HPV-related OPCs o Other types: 18, 33 and 35 OPC data were pooled from studies for which type-specific HPV detection was performed. Guo T, et al. Cancer. 2016

61 Guo T, et al. Cancer CURRENT PROPHYLACTIC HPV VACCINES Three US FDA-Approved HPV Vaccines Approved for the prevention of anogenital cancer, precancer, and warts, but not for OPC. The current body of evidence is insufficient to determine the efficacy of these vaccines within the context of oral HPV infection or OPC.

62 Surgeons Radiation Oncology Oncology Family Medicine Radiology, Pathology Endocrinology Reconstructive surgery Nursing, IPO Speech Therapy OT, PT Nutrition Social Services Palliative care HEAD AND NECK TEAM

63 ADVISE FOR PATIENTS Vaccination Consult for a non-tender neck mass Not all sore throats are tonsillitis Go back to see your doctor if it does not get better Quit smoking Don t quit sex

64 CONCLUSIONS OPC: an emerging epidemic HPV related Inter-disciplinary care De-escalation of treatment New paradigms Less intense XRT for small tumors Neo-adjuvant chemo followed by surgery (and no radiation) Immunotherapy Improved public knowledge regarding the etiologic connection between HPV and OPC may increase vaccine uptake in men

65 THANK YOU

Objectives. HPV Classification. The Connection Between Human Papillomavirus and Oropharyngeal Cancer 6/19/2012

Objectives. HPV Classification. The Connection Between Human Papillomavirus and Oropharyngeal Cancer 6/19/2012 The Connection Between Human Papillomavirus and Oropharyngeal Cancer Jennifer L. Cleveland, DDS, MPH Dental Officer/Epidemiologist OSAP Annual Symposium June 23, 2012 Atlanta, GA National Center for Chronic