Under-appreciated Cancers Associated with HPV Texas Immunization Summit

Transcription

1 Under-appreciated Cancers Associated with HPV 2014 Texas Immunization Summit Erich M. Sturgis, MD, MPH Professor Department of Head & Neck Surgery Department of Epidemiology No C.O.I., disclosures, or off-label

2 I do not have any relevant conflicts of interest to disclose.

3 Epidemiology Pathophysiology Epidemic Demographics Clinical Implications Presentation Prognosis Staging Second ca risk Prevention

4 Spectrum of Head & Neck Oncology skin Environmental Exposures & Host Susceptibility

5 H&N Squamous Cell Carcinomas Nose/Paranasal Sinuses Nasopharynx Oropharynx soft palate tonsil base of tongue post pharyngeal wall Oral Cavity hard palate retromolar trigone oral tongue floor of Mouth mandibular gingiva buccal mucosa labial mucosa maxillary gingiva Hypopharynx pyriform sinus post-cricoid post pharyngeal wall Larynx supraglottis glottis subglottis

6 Genital HPV Infection Most females & males will be infected with at least one HPV type at some point 80 million Americans currently infected 14 million new infections/year in the US the most common STD most common in those in their teens & early 20s Jemal A et al. J Natl Cancer Inst 2013;105:

7 HPV Prevalence among Women by Age (with normal cytology) D. Forman et al. Vaccine 2012

8 Oral HPV prevalence by age

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10 2008 Nobel Prize in Physiology or Medicine Harold zur Hausen, M.D.

11 HPV Infection Most people will never know that they have been infected Most early HPV-associated cancers are asymptomatic Jemal A et al. J Natl Cancer Inst 2013;105:

12 HPV Infection & Progression to Cancer Schematic

13 C.T. Allen, et al. Laryngoscope 2010

14 Epidemiology Pathophysiology Epidemic Demographics Clinical Implications Presentation Prognosis Staging Second ca risk Prevention

15 J Natl Cancer Inst 2013

16 George Papanikolaou( )

17 Annual burden of genital HPV-related disease (U.S. females) 4,000 cervical cancer deaths 10,846 new cases of cervical cancer 330,000 new cases of HSIL: CIN2/3 (high grade cervical dysplasia) 1 million new cases of genital warts 1.4 million new cases of LSIL: CIN1 (low grade cervical dysplasia) 3 million cases & $7 billion American Cancer Society. 2008; Schiffman Arch Pathol Lab Med. 2003; Koshiol Sex Transm Dis. 2004; Insinga, Pharmacoeconomics, 2005

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19 Trends in Incidence of Cervical Ca. (Globocan 2012; age standardized) Globocan.iarc.fr

20 Jemal A, et al. J Natl Cancer Inst 2013

21 EMS Giovino CA. Prev Med Chaturvedi AK, et al. JCO 2011.

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23 Trends in Cancer Incidence & Number Oropharynx vs. Cervical Chaturvedi AK, et al. JCO 2011.

24 Prevalence of HPV16+ Tumors Trends in Stockholm 70% 60% 50% HPV16+ 40% 30% 20% 10% 0% 1970s 1980s 1990s 2000s 203 Tonsillar Carcinomas in Swedish Cancer Registry, Stockholm Region EMS Hammarstedt L, et al. Int. J. Cancer 2006;

25 HPV+ Prevalence among 271 Oropharyngeal Cancers Trends in SEER (Hawaii, L.A., Iowa) Mork, NEJM % of 18 OP cancers HPV16 DNA + Strome, Clin Ca Res % of 52 OP cancers HPV DNA+ D Souza, NEJM % of 100 OP cancers HPV16 DNA+ Li and Sturgis 69% of 392 OP cancers HR-HPV ISH+ 82% of 397 OP cancers HPV16 DNA+ 91% of 332 OP cancers p16+ Chaturvedi AK, et al. JCO 2011.

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27 Vulva Anus Vagina

28 New Cancers at HPV-related Sites Presenting to MD Anderson ( ) 500 Oropharynx 400 Cervix 300 Anus 200 Vulva 100 Penis 0 Vagina

29 Epidemiology Pathophysiology Epidemic Demographics Clinical Implications Presentation Prognosis Staging Second ca risk Prevention

30 Rates of HPV-Associated Cancer & Median Age at Dx Females, United States, *Vaginal cancer statistics for women between ages 20 & 39 not shown because there were < 16 cases. Watson et al. HPV-associated cancers US, MMWR 2012;61:

31 Rates of HPV-Associated Cancer & Median Age at Dx Males, United States, *Penile cancer statistics for men between the ages of 20 & 39 not shown because there were < 16 cases. Watson et al. HPV-associated cancers United States, MMWR 2012;61:

32 Age at Presentation of Patients with SCC of Oropharynx 1944-Jan.2003 (No Prior XRT) Dis Admt Age 20 0 Total N > 4000 p trend < Prospective Database (No. = 2341) Years: Mean: Median:

33 Oropharynx Oral Cavity Incidence Rates (per 100,000 & age-adj. to US 2000) Chaturvedi AK, et al. JCO 2008.

34 Oropharyngeal & Oral Cavity Cancer Age-adjusted Incidence in United States Males Oral Cavity Females Oropharynx Chaturvedi AK, et al. JCO 2008.

35 Public Health Implications HPV epidemic oropharynx, anal, & vulvar Without novel screening or tx of premalignancy, 30 years of increasing burden of these cancers Cost of cervical screening/tx ~ $7B Cervix is major problem in under served pop.

36 Epidemiology Pathophysiology Epidemic Demographics Clinical Implications Presentation - MAM; limited smk; silent Prognosis Staging Second ca risk Prevention

37 3891 patients with incident oropharyngeal cancer presenting to MDACC 61%

38 Presenting Signs & Symptoms Oropharynx silent Oral Cavity painful/visible lesion persistent ulcer red or white patch Silent Primaries neck mass ear pain painful swallowing difficulty swallowing Larynx supraglottis- silent glottis- horseness

39 JAMA Otolaryngol Head Neck Surg 2014;():.doi: /jamaoto JAMA Otolaryngol Head Neck Surg. 2014;():. doi: /jamaoto Date of download: 3/24/2014 Copyright 2014 American Medical Association. All rights reserved.

40 Oropharynx

41 FNA Biopsy Incisional Biopsy cytology histology

42 TNM Staging T1 T2 T3 T4a T4b M1

43 Stage, Grade, & Site Lower T-category Higher N-category Higher grade Tonsil & BOT Higher Stage

44 86%

45 Epidemiology Pathophysiology Epidemic Demographics Clinical Implications Presentation Prognosis - excellent if standard of care Staging Second ca risk Prevention

46 Treatment - Oropharynx Staging/HPV/Smoking: Low Risk Intermediate Risk High Risk XRT (transoral surgery- selected) Chemo + XRT Chemo + XRT *Clinical trials should be offered where available 5yr Survival 80-90% 60-80% 30-60%

47 SEER 5yr Relative Survival Rates Larynx Oral Cavity Oropharynx EMS

48 Ten-Year Overall Survival of M0 Oropharyngeal Cancer Patients by Decade Admitted Died Last Contac Cumulative Proportion Surviving P Value from Log Rank Test (compared to previous decade) < Total M0 = , N = , N = , N = , N = , N = Months from Presentation at MDACC

49 Author, Year N Assays Fakhry, et al. ECOG 2399 JNCI 2008 *Ang, et al. RTOG 0129 NEJM 2010 *Richin, et al. TROG JCO 2010 *Posner, et al. TAX324 Ann Onc 2011 Lassen, et al. DHANCA-5 Rad Oncol 2011 Outcome HPV-postive vs. HPV-negative Endpoint HR (95% CI) P-Value 96 ISH, p16, etc. Tumor progression 0.27 ( ) ISH and p p16 Overall survival Prog-Free Survival Overall Survival Failure-Free Survival 0.42 ( ) 0.49 ( ) 0.36 ( ) 0.39 ( ) <0.001 < PCR (E6-E7) Overall Survival 0.20 ( ) < p16 *Oropharynx only HPV & Prognosis Multi-institutional Clinical Trials Dz-specific survival Overall survival 0.58 ( ) 0.62 ( ) <0.001 Ang & Sturgis, Sem Rad Onc 2011

50 July 1, 2010; 363:24-35

51 Epidemiology Pathophysiology Epidemic Demographics Clinical Implications Presentation Prognosis Staging - Stage IV (small primary + nodes) Second ca risk Prevention

52 Typical TNM Staging Small Primary + Multiple Nodes = Stage IV T1 T2 T3 T4a T4b X X X M1

53 Before 1995 After 1995

54 Epidemiology Pathophysiology Epidemic Demographics Clinical Implications Presentation Prognosis Staging Second ca risk - low but consider HPV sites Prevention

55 EAR (excess absolute risk) of SPM (2nd primary malignancy) after Index H&N Cancer within SEER Registry Morris, LGT et al. JCO 2011

56 Head & Neck (epub)

57 Second Primary Site Second Primary Cancers in Men Segregated by Marrital Status SEER Database All Anogenital 0BSERVED / EXPECTED nd ORAL/PHARYNGEAL INDEX CANCER primary Anus Penis Prostate Bladder Colon All OC/Pharynx 2 nd primary ANOGENITAL INDEX CANCER Tonsil Tongue Prostate Bladder Colon Ever Married Never Married Sikora, Morris, & Sturgis Arch Oto-HNS, 2009

58 Epidemiology Pathophysiology Epidemic Demographics Clinical Implications Presentation Prognosis Staging Second ca risk Prevention - Vaccination

59 Estimated, % Prevalence of HPV 6 and 11 Diseases Commonly Associated with HPV 100% Nasal NPC? Palate Larynx % 60% 40% 20% 0% CIN 1 VIN 1 Genital RRP Warts 1 million new cases of genital warts / yr in US million CIN 1 annually in US Anal Vulvar Vaginal Penile Cervical 95 Trachea

60 Gardasil (Merck) Two components: HPV Types 6, 11, 16, 18 L1 virus-like particles (VLPs) Proprietary aluminum adjuvant (AAHS) VLPs manufactured in Saccharomyces cerevisiae (yeast) Yeast-derived vaccines given to millions of children and adults 0-, 2-, 6-month dosing regimen Cervarix (GSK) Two components: HPV Types 16, 18 L1 virus-like particles (VLPs) Proprietary adjuvant (ASO4) 0-, 2-, 6-month dosing regimen Some protection from 31 and 45

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64 2013

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67 Conclusions HPV epidemic - demographic, behavior, survival Staging system needs modification. 2nd primary is less of a problem (different sites?). Vaccination is an imperative.

68 Thank You George Harrison Oropharynx Cancer Hafner & Sturgis. J Texas Dent Assoc 2008

69 Frequently Asked? How & when did I get HPV? Is my partner or family at risk? Should my partners be screened for HPV or H&Nca? Should I, my partner, or kids be vaccinated?

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