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INFECTIOUS DISEASE Update

A CPMC Regional CME Event. INFECTIOUS DISEASE Update. - Microbiome and Emerging Infections. Saturday October 19, 2013. HPV UPDATE: Head and neck Carcinoma. Gerald Kangelaris, MD San Francisco Otolaryngology. No Financial Disclosures. HPV In the media. HPV In the media.

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INFECTIOUS DISEASE Update

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  1. A CPMC Regional CME Event INFECTIOUS DISEASE Update - Microbiome and Emerging Infections Saturday October 19, 2013

  2. HPV UPDATE:Head and neck Carcinoma Gerald Kangelaris, MD San Francisco Otolaryngology

  3. No Financial Disclosures

  4. HPV In the media

  5. HPV In the media

  6. HPV In the media

  7. CONCERNED PATIENTS

  8. Goals Describe HPV associated head & neck cancer Understand at-risk population Appreciate disease presentation Describe basics of treatment and outcomes Improve ability to counsel patients!

  9. OUTLINE – hpv in head & neck carcinoma Virology Epidemiology Carcinogenesis Presentation Treatment & Outcomes Future Directions

  10. Virology http://hpvvirusinwomen.com/images/hpv_virus_in_women3.jpg • HPV • dsDNA virus • 100+ strains isolated • 15 strains high risk • Types 16 & 18 • Genitals • Anus • Oropharynx

  11. Virology http://faculty.ksu.edu.sa/dralghamdi/Pictures%20Library/طبقات%20الجلد%20skin%20layers.jpg

  12. Virology http://upload.wikimedia.org/wikipedia/commons/b/b4/Normal_Epidermis_and_Dermis_with_Intradermal_Nevus_10x.JPG http://www.lab.anhb.uwa.edu.au/mb140/corepages/Lymphoid2/images/tns02he.jpg

  13. Virology http://www.region3sweetadelines.org/documents/AIM%202011/pharynx.jpg • Head & Neck Sites • Palatine tonsil • Tongue base

  14. epidemiology D’Souza G, Kreimer A, et al. Case-Control Study of Human Papillomavirus and Oropharyngeal Cancer. N Eng J Med 2007, 356:1944-56.

  15. epidemiology ChaturvediAK, Engels EA, et al. Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States. J ClinOnc2011. 29(32):4294-4301. • Head and Neck Cancers • Overall decreasing • Oropharynx increasing • OP Cancer Epidemic • OP HPV (-) • 2.0  1.0 per 100,000 • OP HPV (+) • 0.8  2.6 per 100,000

  16. epidemiology http://quittea.com/wp-content/uploads/2012/06/Old-Guy-Smoking-Cigar.jpg http://i.telegraph.co.uk/multimedia/archive/01589/Lorna-Gobey_1589754c.jpg Typical Head & Neck Cancer Patient

  17. epidemiology http://maennling.com/wp/wp-content/uploads/2012/11/DSC_6796.jpg http://ak9.picdn.net/shutterstock/videos/4194004/preview/stock-footage-smart-caucasian-middle-aged-man-looking-to-the-camera-in-the-park-close-up-portrait.jpg HPV Oropharynx Cancer Patient

  18. epidemiology Gillison ML, Broutian T, et al. Prevalence of Oral HPV Infection in the United States, 2009-2010. J Am Med Assoc2012. 307(7):693-703. HPV (+) OPSCC as Sexually Transmitted Disease • Presence of HPV in Oral Samples Increases With… • Being sexually active • Early age sexual activity • Increasing # oral sex partners • Increasing # vaginal & anal sex partners • Male • No difference if hetero- or homosexual/bisexual

  19. epidemiology Gillison ML, Broutian T, et al. Prevalence of Oral HPV Infection in the United States, 2009-2010. J Am Med Assoc2012. 307(7):693-703. HPV (+) OPSCC as Sexually Transmitted Disease Presence of HPV in Oral Samples…

  20. epidemiology D’Souza G, Kreimer A, et al. Case-Control Study of Human Papillomavirus and Oropharyngeal Cancer. N Eng J Med 2007, 356:1944-56. HPV (+) OPSCC as Sexually Transmitted Disease • HPV (+) vs. HPV (-) OPSCC • Lifetime # Oral Sex Partners • 0 partners OR 1.0 • 1-5 partners OR 3.8 • 6+ partners OR 8.6 • Lifetime # Vaginal Sex Partners • 0-5 partners OR 1.0 • 6-25 partners OR 2.7 • 26+ partners OR 4.2

  21. epidemiology

  22. Carcinogenesis • Six non-structural proteins • Two viral oncoproteins E6 and E7 • E6 and E7 increased activity in high-risk HPV strains http://img.medscape.com/fullsize/migrated/585/223/erm585223.fig2.jpg • HPV DNA • Two capsid proteins, L1 and L2

  23. Carcinogenesis • E6 • Degradation of tumor suppressor p53 • Prevents apoptosis • E7 • Loss of retinoblastoma (Rb) tumor suppressor • Accumulates p16 • Pushes cells from G1  S phase

  24. presentation http://www.nidcr.nih.gov/NR/rdonlyres/04B2E6CA-B032-47C0-BC09-D995D6655AA6/18010/OralCancerFig14High.jpg Palatine or Lingual Tonsil Location

  25. presentation • Symptoms • Painful oral lesion • Dysphagia or odynophagia • Bleeding • Asymmetry • Trismus • Otalgia • Hypoesthesia • Asymptomatic!

  26. presentation http://www.ghorayeb.com/files/carcinoma_of_tonsil.jpg

  27. presentation http://www.ghorayeb.com/files/Tongue_Sq_Cell_Ca_700_x_500.jpg

  28. presentation • Differential Diagnosis • Infectious • Benign lesions • Neoplastic • Inflammatory

  29. presentation http://quebal.icebergcms.com.au/images/product/image/enl_who_circumvallate_papillae.jpg

  30. presentation http://www.capedental.com/cdmain/wp-content/uploads/2011/05/IMG_3641.jpg

  31. presentation http://www.aafp.org/afp/2002/0901/afp20020901p831-f3.jpg http://1.bp.blogspot.com/-wotdvG47uXI/T3DkTZOhIZI/AAAAAAAAKPQ/ujuwutpvCyo/s1600/CysticNodesHPV.JPG • High Rates Nodal Metastases • Often Tumor Undetectable at Primary Site

  32. presentation • Consider HPV(+) OPSCC • Neck mass persisting for 4+ weeks, unresponsive to medical therapy • Upper jugular chain • Firm, discrete, mobile, nontender • May be asymptomatic & non-visible at primary site! • Persistent OP sore throat 4+ weeks, unresponsive to medical therapy • Tonsillar asymmetry, otalgia • Advanced disease • Dysphagia, pharyngeal bleeding, trismus, voice changes

  33. presentation • Workup • FNA neck mass • US guidance may improve yield in cystic masses • Imaging • Contrast enhanced CT / MRI neck • CXR • OHNS evaluation • Fiberopticnasopharyngoscopy • Exam under anesthesia, biopsies

  34. TREATMENT & OUTCOME • Treatment Options • Concurrent chemoradiation • Surgery with adjuvant radiation, +/- chemotherapy

  35. TREATMENT & OUTCOME Improved survival in HPV (+) OPSCC tumors Ang KK, Harris J, et al. Human Papillomavirus and Survival of Patients with OropharyngealCancer.NEng J Med 2010. 363(1):24-35.

  36. TREATMENT & OUTCOME O’Rorke MA, Ellison MV, et al. Human Papillomavirus Related Head and Neck Cancer Survival: A Systematic Review and Meta-Analysis. Oral Oncology 2012. 48:1191-1201. • Improved survival in HPV (+) OPSCC tumors • 53% better overall survival • 74% better disease specific survival • Improvements in progression free survival, disease free survival

  37. TREATMENT & OUTCOME • Mechanisms for Improved Outcomes • Lack of field cancerization • Increased sensitivity to radiation therapy • Degraded wild-type p53, not mutations • Immune response

  38. Future directions • De-intensification strategies • Lower dose of radiation therapy • Targeted chemotherapeutics • Surgery with de-escalation of adjuvant treatment http://www.healthspablog.org/wp-content/uploads/2010/11/radiotherapy-6D.jpg http://oralcancernews.org/wp/wp-content/uploads/2011/09/robotic_surgery03.jpg

  39. Future directions Vaccination http://www.pulsetoday.co.uk/Pictures/web/d/v/a/Cervarix_vaccine_pack_hpv_cervical.jpg http://www.thedailysheeple.com/wp-content/uploads/2012/10/GARDASIL111308.jpg

  40. Future directions Vaccination http://www.skepticalraptor.com/blog/wp-content/uploads/2012/10/gardasil-ad1.jpg http://1.bp.blogspot.com/-ejglTzhvHAg/T6CydnVyaxI/AAAAAAAAAOs/pGVsBwnF3Pw/s1600/new%2Bdoc_1.jpg

  41. Future directions Vaccination http://1.bp.blogspot.com/-0DPj7SzNye0/TzW3wpLXojI/AAAAAAAAB_I/DkBrrVtXdfA/s400/gardasil4-1.jpg http://gaia-health.com/gaia-blog/wp-content/uploads/2012/11/Say-No-to-Cervarix-and-Gardasil.jpg

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