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
HPV IN THE MEDIA
CONCERNED PATIENTS
GOALS
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Describe HPV associated head & neck cancer
Understand at-risk population
Appreciate disease presentation
Describe basics of treatment and outcomes
• Improve ability to counsel patients!
OUTLINE – HPV IN HEAD & NECK CARCINOMA
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Virology
Epidemiology
Carcinogenesis
Presentation
Treatment & Outcomes
Future Directions
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
VIROLOGY
http://faculty.ksu.edu.sa/dralghamdi/Pictures%20Library/‫طبقات‬%20‫الجلد‬%20skin%20layers.jpg
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
VIROLOGY
• Head & Neck Sites
- Palatine tonsil
- Tongue base
http://www.region3sweetadelines.org/documents/AIM%202011/pharynx.jpg
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.
EPIDEMIOLOGY
• 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
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.
EPIDEMIOLOGY
• Typical Head & Neck Cancer Patient
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
EPIDEMIOLOGY
• HPV Oropharynx Cancer Patient
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
EPIDEMIOLOGY
HPV (+) OPSCC as Sexually Transmitted Disease
• Presence of HPV in Oral Samples Increases
With…
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Being sexually active
Early age sexual activity
Increasing # oral sex partners
Increasing # vaginal & anal sex partners
Male
No difference if hetero- or homosexual/bisexual
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.
EPIDEMIOLOGY
HPV (+) OPSCC as Sexually Transmitted Disease
• Presence of HPV in Oral Samples…
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.
EPIDEMIOLOGY
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
D’Souza G, Kreimer A, et al. Case-Control Study of Human Papillomavirus and Oropharyngeal Cancer. N Eng J Med 2007, 356:1944-56.
EPIDEMIOLOGY
HPV (+) OPSCC
HPV (-) OPSCC
Younger (<50 years)
Older (>60 years)
Never / Mild Smoker
Heavy Smoker
Mild / Mod Alcohol
Heavy Alcohol
High Sexual Exposure
Low Sexual Exposure
Higher Socioeconomic Status
Lower Socioeconomic Status
Increasing Incidence
Decreasing Incidence
CARCINOGENESIS
• HPV DNA
- Two capsid proteins, L1 and L2
- 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
CARCINOGENESIS
• E6
- Degradation of tumor suppressor p53
- Prevents apoptosis
• E7
- Loss of retinoblastoma (Rb) tumor suppressor
- Accumulates p16
- Pushes cells from G1  S phase
PRESENTATION
• Palatine or Lingual Tonsil Location
http://www.nidcr.nih.gov/NR/rdonlyres/04B2E6CA-B032-47C0-BC09-D995D6655AA6/18010/OralCancerFig14High.jpg
PRESENTATION
• Symptoms
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Painful oral lesion
Dysphagia or odynophagia
Bleeding
Asymmetry
Trismus
Otalgia
Hypoesthesia
• Asymptomatic!
PRESENTATION
http://www.ghorayeb.com/files/carcinoma_of_tonsil.jpg
PRESENTATION
http://www.ghorayeb.com/files/Tongue_Sq_Cell_Ca_700_x_500.jpg
PRESENTATION
• Differential Diagnosis
- Infectious
- Benign lesions
- Neoplastic
- Inflammatory
PRESENTATION
http://quebal.icebergcms.com.au/images/product/image/enl_who_circumvallate_papillae.jpg
PRESENTATION
http://www.capedental.com/cdmain/wp-content/uploads/2011/05/IMG_3641.jpg
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
PRESENTATION
• Consider HPV(+) OPSCC
- Neck mass persisting for 4+ weeks, unresponsive to
medical therapy
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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
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Tonsillar asymmetry, otalgia
- Advanced disease
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Dysphagia, pharyngeal bleeding, trismus, voice changes
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
TREATMENT & OUTCOME
• Treatment Options
- Concurrent chemoradiation
- Surgery with adjuvant radiation, +/- chemotherapy
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.
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.
TREATMENT & OUTCOME
• Mechanisms for Improved Outcomes
- Lack of field cancerization
- Increased sensitivity to radiation therapy
• Degraded wild-type p53, not mutations
- Immune response
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
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
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
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