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

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Presentation on theme: "INFECTIOUS DISEASE UPDATE A CPMC Regional CME Event - Microbiome and Emerging Infections Saturday October 19, 2013."— Presentation transcript:

1 INFECTIOUS DISEASE UPDATE A CPMC Regional CME Event - 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

6

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

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

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 Chaturvedi AK, Engels EA, et al. Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States. J Clin Onc 2011. 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 Assoc 2012. 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 Assoc 2012. 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 partnersOR 1.0 1-5 partnersOR 3.8 6+ partnersOR 8.6 - Lifetime # Vaginal Sex Partners 0-5 partnersOR 1.0 6-25 partnersOR 2.7 26+ partnersOR 4.2

21 EPIDEMIOLOGY HPV (+) OPSCCHPV (-) OPSCC Younger (<50 years)Older (>60 years) Never / Mild SmokerHeavy Smoker Mild / Mod AlcoholHeavy Alcohol High Sexual ExposureLow Sexual Exposure Higher Socioeconomic StatusLower Socioeconomic Status Increasing IncidenceDecreasing Incidence

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

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

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

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 Fiberoptic nasopharyngoscopy 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 Oropharyngeal Cancer.N Eng J Med 2010. 363(1):24-35.

36 TREATMENT & OUTCOME Improved survival in HPV (+) OPSCC tumors - 53% better overall survival - 74% better disease specific survival - Improvements in progression free survival, disease free survival 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.

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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