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Oropharynx cancer and HPV in 2019

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The increasing role of HPV infections and oropharynx cancer, understanding the epidemiology and impact on prognosis and treatment

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Oropharynx cancer and HPV in 2019

  1. 1. Oropharynx Cancer 2019 Oropharyngeal cancer is the fastest-rising cancer among young white men in the United States aboutcancer.com
  2. 2. Head & Neck cancer has decreased concomitantly with declining tobacco smoking rates, oropharynx incidence has significantly increased in recent years. The proportion of OPX caused by HPV has grown from 16% in the early 1980s to nearly 80%, and is expected to exceed cervix by 2020 Expert Rev Anticancer Ther. 2015 Jan; 15(1): 35–49.
  3. 3. HPV Infection and Cancer of the Oropharynx Non-HPV = Yellow, HPV = blue Primarily Tonsil and Base of Tongue HPV-positive HNSCCs of the oral cavity and larynx the prevalence of HPV-positive tumor status is much lower (less than 10%) than in the oropharynx, and the clinical significance is unclear
  4. 4. Disease arising in the tonsillar crypts in the lymphoid tissue in the tonsils and base of the tongue
  5. 5. 1. Epidemiology 2. Vaccination 3. Clinical Presentation 4. Treatment and Outcome HPV and Oropharynx Cancer
  6. 6. 2019 Statistics Pharynx Cancer New Cases Deaths Male Female Male Female 14,450 3,420 2,660 790 1.6% 0.4% 0.8% 0.3% M:F = 4.2: 1
  7. 7. Infectious Agents Certain infectious agents, including viruses, bacteria, and parasites, can cause cancer or increase the risk that cancer will form. Epstein-Barr Virus (EBV) Hepatitis B Virus and Hepatitis C Virus (HBV and HCV) Human Immunodeficiency Virus (HIV) Human Papillomaviruses (HPVs) Human T-Cell Leukemia/Lymphoma Virus Type 1 (HTLV-1) Kaposi Sarcoma-Associated Herpesvirus (KSHV) Merkel Cell Polyomavirus (MCPyV) Helicobacter pylori (H. pylori) Opisthorchis viverrini Schistosoma hematobium cancer.gov/about-cancer/causes-prevention/risk/infectious-agents
  8. 8. 0 1 2 3 4 5 6 7 8 1959 1979 1996 Tonsillectomy Rates in the US (cases per 1000) Dramatic decline in routine tonsillectomies since 1959
  9. 9. Having a tonsillectomy as a child may reduce the risk of getting tonsil cancer by 60 – 85% Cancer Prev Res; 2015; 8(7); 583–9 Br J Cancer 2016 Mar 29; 114(7): 832–838
  10. 10. The Impact of Tonsillectomy upon the Risk of Oropharyngeal Carcinoma Diagnosis and Prognosis in the Danish Cancer Registry Fakhry Cancer Prev Res; 8(7); 583–9 From 1977 to 2012, the incidence of tonsillectomies significantly decreased, whereas the incidence of oropharyngeal carcinoma significantly increased. 77% of tonsil carcinomas diagnosed in Denmark between 2000 and 2010 were HPV-related, Concurrent with a change in sexual behavior, tonsillectomy for hypertrophic tonsils and recurrent tonsillitis have lost previously held general acceptance Tonsillectomy was not associated with risk of oropharyngeal carcinoma or malignancies of other anatomic sites, including base of tongue. However, tonsillectomy significantly reduced risk of diagnosis with tonsil carcinoma (RR, 0.40.) The risk of diagnosis with tonsil carcinoma at age <60 years was significantly decreased (RR 0.15) after tonsillectomy.
  11. 11. Previous tonsillectomy modifies odds of tonsil and base of tongue cancer Zevallos Br J Cancer 2016 Mar 29; 114(7): 832–838.) Age of Tonsillectomy Base of Tongue Tonsil No 1 1 <13 y 2.46 0.19 13 + .33 .32 Having tonsillectomy at young age may cause BOT tonsil hypertrophy and lower tonsil cancer but increase base of tongue cancer risk
  12. 12. Previous tonsillectomy modifies odds of tonsil and base of tongue cancer Zevallos Br J Cancer 2016 Mar 29; 114(7): 832–838.) North Carolina Data Age of Tonsillectomy Base of Tongue Tonsil No 1 1 <13 y 2.46 0.19 13 + 0.33 0.32 Having tonsillectomy at a young age may cause BOT lymphoid hypertrophy and lower tonsil cancer but increase base of tongue cancer risk by 246% by 67% by 81% by 68%
  13. 13. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010 2020 Men Women Declining Smoking in the US Humphrey Bogart Dead at 57 from esophagus cancer in 1957
  14. 14. Decline in Smoking Steep decline since 1960’s Less dramatic decline in women Time 1975-82 1982-91 91-2008 2008-15 Men + 1.5% -0.5% -1.7% -2.9% Women +5.6% +3.4% +.5% -1.5% Lung Cancer Incidence Men started cutting back on smoking in the 60’s and lung cancer started to decline in the 80’s. Women cut back later and cancer didn’t decline till the millennium
  15. 15. During the 60’s People became more ‘affectionate’
  16. 16. 1920 1940 1960 1980 2000 Year smoking H&N cancer oropharynx Other H&N 225% Increase in HPV+ vs 50% decrease in HPV -
  17. 17. Dramatic Rise in HPV + Tonsil Cancer Smoking The timing between exposure to HPV and the development of oropharyngeal cancer probably exceeds 10 years HPV Most Common HPV + HPV -
  18. 18. Dramatic Rise in HPV + Tonsil Cancer HPV Most Common Smoking The timing between exposure to HPV and the development of oropharyngeal cancer probably exceeds 10 years HPV + HPV -
  19. 19. Increasing HPV in Oropharynx Cancer HPV 16 Viral Load Observed Corrected JCO 29, no. 32 (November 10 2011) 4294-4301. The proportion of OPX caused by HPV has grown from 16% in the early 1980s to nearly 80%, and is expected to exceed cervix by 2020
  20. 20. HPV Types
  21. 21. HPV = Human Papillomavirus More than 200 varieties of human papillomavirus (HPV) exist, double- stranded DNA viruses that infect only humans HPV is a very common virus; nearly 80 million people—about one in four— are currently infected in the United States. Base of the tongue and tonsillar cancer /HPV-16 genotype causative agent in many, Other high-risk HPV genotypes, such as HPV-18, 31, or 33, are also causative but are less common
  22. 22. HPV Prevalence High-risk oral HPV means tested positive to one or more of the 14 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, or 68) from an oral rinse sample.
  23. 23. Prevalence of high-risk oral HPV among adults aged 18–69, by race and Hispanic origin and sex: United States, 2011–2014
  24. 24. HPV Prevalence Oral Human Papillomavirus Infection: Differences in Prevalence Between Sexes and Concordance With Genital Human Papillomavirus Infection, NHANES 2011 to 2014. Ann Intern Med. 2017;167(10):714. Test Men Women Oral HPV + 11.5% 3.2% High risk HPV 7.3% 1.4% Oral HPV 16 1.8% 0.3%
  25. 25. Understanding personal risk of oropharyngeal cancer: risk-groups for oncogenic oral HPV infection and oropharyngeal cancer. Oncogenic oral HPV DNA is detected in 3.5% of all adults age 20-69 years; Among men 50-59 years old: 8.1% have an oncogenic oral HPV infection, 2.1% have an oral HPV16 infection 0.7% will 'ever' develop oropharyngeal cancer in their lifetime. Ann Oncol. 2017 Dec 1;28(12):3065-3069
  26. 26. HPV Carcinogenic Mechanism
  27. 27. In the Cervix HPVs infect basal cells of squamous epithelia through sites of mechanical trauma. Infections with high-risk HPVs can lead to dysplasia and carcinoma in situ and to invasive squamous cell carcinoma. Progression is a rare and slow process and many lesions
  28. 28. Tonsils are large non-encapsulated (or partially encapsulated) masses of lymphoid tissue, that lie in the walls of the pharynx and nasopharynx and at the base of the tongue. The luminal surface of the tonsils are covered with a stratified squamous epithelium (in common with the oral epithelia). The tonsils have many invaginations which form blind crypts. HPV cancer arises from the epithelium lining the crypts
  29. 29. HPV and Oropharyngeal Cancer Latency from infection: Cervix (29 years) peak infection (20y) to cancer (49y) OPX / HPV (10-30y) peak infection (25-30 and 55-60) and cancer 58 - 61y HPV Vaccine impact expected by 2050
  30. 30. Latency from Infection to Cancer 20 – 30 years
  31. 31. Projected Numbers of New Cases in the Future J Clin Oncol 2011;29:4294
  32. 32. HPV-Associated Cancer Rates by State 2011–2015 Rates are per 100,000
  33. 33. 12,885 / 803 = 16 X cdc.gov/cancer/hpv/statistics/ cases.htm
  34. 34. HPV Oropharynx Cancer Rate 2011 – 2015 Gender White Black Male 8.8 6.6 Female 1.8 1.4 8.8 / 1.8 = 4.9 X cdc.gov/cancer/hpv/statistics/headneck
  35. 35. What about the partner? If one person in a heterosexual couple has human papillomavirus (HPV), there's a 20 percent chance his or her partner will pick up the virus within six months, a new study concludes. The study, the largest-yet analysis of HPV transmission rates, found no difference between male-to-female transmission rates and female-to-male transmission rates. The new study was published Oct. 7, 2011 in the Journal of Infectious Diseases
  36. 36. What about the partner? Oncogenic oral HPV infection is detectable in the majority of patients with HPV associated oropharyngeal cancer, but the incidence of such HPV infection in long-term sexual partners is not increased beyond that seen in the general population.
  37. 37. What about the partner? 164 patients with oropharyngeal cancer, oral HPV was detected in 65 percent of cases, and an oncogenic HPV strain was identified in 61 percent Among the 93 partners available for testing, the overall incidence of HPV infection was 4 percent, and only one had the oncogenic HPV-16. These findings suggest that most partners effectively clear any active infection to which they are exposed. J Clin Oncol. 2014;32(23):2408
  38. 38. Discussing the diagnosis of HPV- OSCC: Common questions and answers Fakhry , Gypsyamber D’Souza. Oral Oncology 49 (2013) 863–871
  39. 39. Tonsil Base of Tongue Tonsil Tonsil and Base of Tongue, what about other head and neck sites?
  40. 40. HPV and Other H&N Cancers 148 studies, including 12,163 cases of squamous cell carcinoma of the head and neck HPV prevalence rates HPV-16 oropharyngeal (45.8%) 40.6% oral cavity (24.2%) 14.9% laryngeal cancers (22.1%) 13.3% Lancet Oncol. 2014 Nov;15(12):1319-31.
  41. 41. HPV and Other H&N Cancers 3680 cases of squamous cell carcinoma of the head and neck prevalence of HPV P16 + oropharyngeal 24.9% 22.4% oral cavity 7.4% 4.4% laryngeal cancers 5.7% 3.5% J Natl Cancer Inst. 2016;108(6)
  42. 42. HPV and Other H&N Cancers 520 head and neck squamous cell carcinomas based on gene expression profiling found that HPV driven tumors accounted for 4.1 percent of non-oropharyngeal cancers HPV associated nonoropharyngeal carcinomas did not appear to have improved overall survival compared with non-oropharyngeal carcinomas not associated with HPV. Chakravarthy A, Henderson S, Thirdborough SM J Clin Oncol. 2016;
  43. 43. Prognostic Value of HPV and P16 Expression in Nasopharyngeal Carcinoma After Chemoradiation IJROBP 2017;99:E340 N = 135 EBV + 62% HPV + 17% Improved OS (overall survival) correlated with EBV-positivity (HR 0.48 ). Worse OS trended toward significance with HPV-positivity (HR 1.63) EBV = Epstein-Barr Virus (causes mononucleosis and is linked to nasopharynx cancer)
  44. 44. Sinonasal Cancer and HPV? https://documents.cap.org/documents/bishop-HPV-head-neck.pdf • HPV + in oropharynx (80%) and uncommon in larynx, hypopharynx and oral cavity (1-5%) • HPV + may be important in sinonasal cancer (21% +) • Trend towards higher survival in this group if p16+ (Bishop JA, et al. Am. J. Surg. Pathol. 2013. 37(6):836-44.) • CAP (College of American Pathologists) guidelines as of 2019 do not recommend routine HPV testing for any of these sites other than oropharynx
  45. 45. P16 or HPV? Real-time PCR to measure HPV-16 viral load and/or immunohistochemistry to detect p16 expression are commonly used The p16 protein functions as a tumor suppressor and is overexpressed in HPV associated cancers Ten percent of those positive by p16 were negative for HPV, and 7 percent of those negative for p16 were positive for HPV. studies using p16 as a surrogate marker for HPV positivity appear to have demonstrated a similar impact on survival AJCC Eighth Edition (2016) is based on p16 (not HPV status)
  46. 46. Why did the AJCC pick p16 as the biomarker rather than HPV? “Direct detection of HPV will not be used as a defining factor due to: • Difficulty in availability • Cost • Failure to stratify survival as well as p16 overexpression”
  47. 47. 1. Epidemiology 2. Vaccination 3. Clinical Presentation 4. Treatment and Outcome HPV and Oropharynx Cancer
  48. 48. Vaccine to Prevent HPV Since mid-2006, a licensed human papillomavirus (HPV) vaccine has been available and recommended (Gardasil) Vaccination coverage with ≥1 dose of any HPV vaccine increased significantly from 53.8% (2012) to 57.3% (2013) adolescent girls 20.8% (2012) to 34.6% (2013) adolescent boys. MMWR July 25, 2014 / 63(29);620-4
  49. 49. www.cdc.gov/vaccines/schedules/index.html
  50. 50. Human papillomavirus vaccination (minimum age: 9 years) Routine and catch-up vaccination HPV vaccination routinely recommended for all adolescents age 11–12 years (can start at age 9 years) and through age 18 years if not previously adequately vaccinated 2- or 3-dose series depending on age at initial vaccination: Age 9 through 14 years at initial vaccination: 2-dose series at 0, 6–12 months (minimum interval: 5 months; repeat dose if administered too soon) Age 15 years or older at initial vaccination: 3-dose series at 0, 1–2 months, 6 months (minimum intervals: dose 1 to dose 2: 4 weeks / dose 2 to dose 3: 12 weeks / dose 1 to dose 3: 5 months; repeat dose if administered too soon) If completed valid vaccination series with any HPV vaccine, no additional doses needed Special situations Immunocompromising conditions, including HIV infection: 3-dose series as above History of sexual abuse or assault: Start at age 9 years Pregnancy: HPV vaccination not recommended until after pregnancy; no intervention needed if vaccinated while pregnant; pregnancy testing not needed before vaccination
  51. 51. www.cdc.gov/vaccines/schedules/index.html
  52. 52. An international randomized trial 14,000 females aged 16 to 26 years. - efficacy 97 percent among the HPV-naïve population large randomized trials in females aged 15 to 25 years. Vaccine efficacy in preventing CIN2 or more severe disease due to HPV vaccine types was: •93 percent among the HPV-naïve population •53 percent among the overall population 5752 women older than 25 years was 22 percent overall. - 91% efficacy for HPV naïve - 22% overall Vaccine works best if HPV-naive
  53. 53. FDA NEWS RELEASE For Immediate Release: October 05, 2018 FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old Gardasil, a vaccine approved by the FDA in 2006 to prevent certain cancers and diseases caused by four HPV types, is no longer distributed in the U.S. In 2014, the FDA approved Gardasil 9, which covers the same four HPV types as Gardasil, as well as an additional five HPV types. Gardasil 9 was approved for use in males and females aged 9 through 26 years.
  54. 54. FDA NEWS RELEASE For Immediate Release: October 05, 2018 In a study in approximately 3,200 women 27 through 45 years of age, followed for an average of 3.5 years, Gardasil was 88 percent effective in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine. Effectiveness of Gardasil 9 in men 27 through 45 years of age is inferred from the data described above in women In a study of 420 women, online daters aged 25 – 65y, annual incidence 25.4% of high- risk HPV in vaginal swabs of which 64% were likely new infections In 1,757 men aged 18 – 59, 45% had genital infections, bimodal peak infections 28 – 32 and larger peak aged 58 – 59. Se despite previous exposure both genders continue to get new infections
  55. 55. HPV Immunization 2017 Percent of 13-15 Vaccinated Healthy People 2020 Target = 80%
  56. 56. Oropharyngeal cancer “is the fastest-rising cancer among young white men in the United States, Routine vaccination against HPV has been recommended since mid-2006 for 11- to 12-year-old girls and for females up to age 26 who have not previously been vaccinated. HPV vaccination has been recommended for males ages 9–26 since 2009. Impact of HPV vaccination on oral HPV infections among young adults in the U.S. Presented ASCO June 5, 2017
  57. 57. Group HPV No Vaccine Vaccinated All high risk 1.61% 0.11% Men high risk 2.13% 0.0% All low risk 4.74% 3.98% Data informing the impact of HPV vaccine on oral disease are limited to studies demonstrating a reduction in oral HPV infection following vaccination J Clin Oncol. 2018;36(3):262
  58. 58. Gardasil The Food and Drug Administration (FDA) has approved three vaccines that prevent infection with disease-causing HPV types: Gardasil®, Gardasil® 9, and Cervarix®. All three vaccines prevent infection with HPV types 16 and 18, two high-risk HPVs that cause about 70% of cervical cancers and an even higher percentage of some of the other HPV-caused cancers. Gardasil also prevents infection with HPV types 6 and 11, which cause 90% of genital warts. Gardasil 9 prevents infection with the same four HPV types plus five additional cancer-causing types (31, 33, 45, 52, and 58). As of May 2017, Gardasil 9 is the only HPV vaccine available for use in the United States. Cervarix and Gardasil are still used in other countries.
  59. 59. 1. Epidemiology 2. Vaccination 3. Clinical Presentation 4. Treatment and Outcome HPV and Oropharynx Cancer
  60. 60. Profile is young, white, male, higher socioeconomic status Asymptomatic cervical adenopathy
  61. 61. 50 yo non-smoker, white male present with a lump in his left neck and the PET scan as noted
  62. 62. A 68-year-old man presented with a mass on the left side of his neck (Panel A) Flexible nasolaryngoscopy showed an exophytic mass on the left base of the tongue and epiglottic vallecula (Panel B). PET Scan showed uptake in the vallecula and bilateral jugulodigastric lymphadenopathy (Panel C).
  63. 63. 53 yo non-smoker presents with a painless lump in the neck and no symptoms inside his throat. On exam 3-4 cm right cervical node and right tonsil ? firm
  64. 64. PET-CT = hot, cystic neck node and small lesion in tonsil Path = squamous cancer, HPV +
  65. 65. Median Age for Women is 62 Rates of HPV-Associated Cancers and Age at Diagnosis Among Women in the United States per Year, 2011–2015
  66. 66. Rates of HPV-Associated Cancers and Age at Diagnosis Among Men in the United States per Year, 2011–2015 Median Age for Men is 61
  67. 67. Rate of New HPV-associated Oropharynx Cancer in 2016
  68. 68. Oropharynx (base of tongue or tonsil)
  69. 69. Typical smoking related oropharynx cancer, presented with months of throat pain radiating into ear
  70. 70. In HPV + cancers the primary may be small and hard to see Squamous Cell Carcinoma. This human papillomavirus- positive tumor presented as a diffuse erythroplakia of the left soft palate and tonsillar region.
  71. 71. Oropharynx Symptoms Based on HPV Status HPV + HPV – Neck mass (51%) Sore Throat (53%) Sore Throat (28%) Dysphagia (41%) Dysphagia (10%) Neck Mass (18%)
  72. 72. Typical Imaging for HPV Oropharynx Cancer CT = large cystic node metastases PET = large neck mass with small primary in tonsil
  73. 73. CT Scan Typical HPV + Patient Large, Lobulated neck mass of lymph nodes with no obvious primary source Neck biopsy = squamous
  74. 74. Ultrasound Typical HPV + Patient Large, Lobulated neck mass of lymph nodes with no obvious primary source
  75. 75. PET Scan Typical HPV + Patient Large lymph node metastases in the neck with no obvious primary source
  76. 76. Small cancer in left base of tongue Large, necrotic lymph node mass Stage IVA Squamous Cancer Left Base of Tongue, HPV +
  77. 77. HPV Oropharynx Cancer 50 yo man, non-smoker presented with cystic neck nodes and occult primary in the base of tongue
  78. 78. HPV Oropharynx Cancer 53 yo man with large cystic neck node and occult primary in base of tongue
  79. 79. HPV Tonsil Cancer 63 yo non-smoker man presents with neck mass and small lesion in tonsil Bx = squamous ISH = high risk HPV IVA (T1N2b)
  80. 80. HPV Tonsil Cancer
  81. 81. 1. Epidemiology 2. Vaccination 3. Clinical Presentation 4. Treatment and Outcome HPV and Oropharynx Cancer
  82. 82. Survival for Tonsil Cancer HPV + HPV -
  83. 83. Patients with HPV-positive tumors were considered to be at low risk, with the exception of smokers with a high nodal stage (i.e., N2b to N3), who were considered to be at intermediate risk; patients with HPV-negative tumors were considered to be at high risk, with the exception of nonsmokers with tumors of stage T2 or T3, who were considered to be at intermediate risk. The 3-year rates of overall survival were 93.0% in the low-risk group, 70.8% in the intermediate-risk group, and 46.2% in the high-risk group. Ang, N Engl J Med 2010; 363:24-35 Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer
  84. 84. Ang, N Engl J Med 2010; 363:24-35 Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer 93% Survival HPV + Nonsmoker Smoker up to N2a Low Risk
  85. 85. Ang, N Engl J Med 2010; 363:24-35 Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer 71% Survival Intermediate Risk HPV + Smoker up to N2b and N3 HPV – Nonsmoker up to N3 or T3
  86. 86. Ang, N Engl J Med 2010; 363:24-35 Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer High Risk HPV - Non – Smoker withT4 or Smoker 46 % Survival
  87. 87. HPV and Survival with Oropharyngeal Cancer N Engl J Med 2010; 363:24-35
  88. 88. Trials of Oropharynx Cancer Improved Survival with HPV + Author Survival HPV + HPV – Ang 82%/3y 57%/3y Ang 86%/3y 60% Gillison 49%/5y 19.6% Posner 82%/5y 35% Rischin 91%/2y 74% Cancer Control July 2016, Vo.23, No 3
  89. 89. Most Patients are Treated with Chemo-Radiation parotid parotid Tonsil cancer Lymph node met Radiation field Radiation field
  90. 90. Chemoradiation for Tonsil Cancer
  91. 91. Chemoradiation for Base of Tongue
  92. 92. Chemoradiation HPV + HPV - JCO September 20, 2010 vol. 28 no. 27 4142-4148
  93. 93. HPV OPC in People over 70. The percent HPV+ increased from 20% (2000) to over 40% (2013). IJROBP 2017;98:858 Survival by HPV HPV + HPV - Years The superior outcome of HPV+ OPC patients versus HPV− counterparts is replicated in the elderly OPC population. Chronologic age lost its prognostication for OS when comorbidity and performance status were taken into account
  94. 94. HPV-Associated Oropharyngeal Cancer Among Elderly Patients: Dramatically Increased Prevalence and Clinical Implications IJROBP 2018;102:E284 The proportion of OPSCC associated with HPV increased from 45.1% in 2010 to 63.3% in 2015 among elderly patients (patients 70 or older). Similar trends in HPV-positivity were seen among subgroups aged 70- 79 (47% to 66) and 80 and older (37% to 53%) during this time period. HPV-positivity was independently associated with improved survival for elderly patients undergoing RT and surgery
  95. 95. Considerable toxicity from combined chemoradiation, interest in ‘de- escalation’ trials
  96. 96. Survival with Oropharynx Cancer HPV + HPV - JCO March 10, 2015 836-845 Problem with the AJCC 7th ed staging system…it’s descriptive but not prognostic for the HPV patients
  97. 97. Survival with Oropharynx Cancer Problem with the AJCC 7th ed staging system…it’s descriptive but not prognostic for the HPV patients
  98. 98. Treatment Strategies HPV + Because the Results are ‘too good’ • Change the staging system (makes no sense that the outcome is the same for all stages) • After re-organize the stage consider de-escalation trials (does everyone need high dose chemoradiation?)
  99. 99. In 2017 (? 2018) Changes the Staging
  100. 100. AJCC 8th Ed 2017 Stage P16 - P16 + I 2cm, N0 4cm, multiple ipsilateral nodes up to 6cm II 4cm , N0 > 4cm, bilat or contralat nodes III >4cm, single 3cm node T4 or nodes > 6cm IV everything else Mets
  101. 101. Point/Counterpoint: Do We De-escalate Treatment of HPV-Associated Oropharynx Cancer Now? And How? American Society of Clinical Oncology Educational Book 39 (May 17, 2019) 364- 372. • There are multiple ways in which treatment can be de-escalated. • Minimally invasive surgery (and skip chemo or radiation) • Lower doses of radiotherapy • Less intense chemotherapy
  102. 102. Minimally Invasive Surgery transoral laser surgery (TLM) transoral robotic surgery (TORS)
  103. 103. Minimally invasive surgery, transoral laser surgery (TLM) or transoral robotic surgery (TORS) and neck dissection to reduce exposure to both radiation and chemotherapy 204 patients (90% HPV+) stage III and IV OPC treated with TLM and neck dissection found 3-year OS and disease-free survival were 86% and 82%, respectively. Locoregional control (LRC) was 97%, and 87% of patients reported either normal swallowing or only episodic dysphagia. Among this cohort, adjuvant therapy was required in 74% patients, with adjuvant RT in 58% and CRT in only 16%. Laryngoscope. 2012;(Suppl 2)S13-S33
  104. 104. NCDB study by Cramer in which 2,463 patients with HPV + OPC survival of low- and intermediate-risk patients with stage I disease who received surgery alone was compared with those who received adjuvant RT and CRT. Interestingly, 33% of patients had already undergone de-escalation. In the low-risk group, 4-year OS was 93.0% with surgery alone versus 95.6% with surgery plus RT and 93.0% with surgery plus CRT. In the intermediate-risk group, 4-year OS was 92.2% with surgery alone versus 93.3% with surgery plus RT and 93.2% with surgery plus CRT. Head Neck 2018;40(3):457-466
  105. 105. E1308: HPV16 and/or p16-positive, stage III-IV OPSCC received three cycles of IC with cisplatin, paclitaxel, and cetuximab. Patients with primary-site cCR to IC received intensity-modulated radiation therapy (IMRT) 54 Gy with weekly cetuximab; Journal of Clinical Oncology 35, no. 5 (February 10 2017) 490-497. Results with Low Dose Radiation
  106. 106. RTOG 1016 Lancet. 2019;393:40-50 Results XRT + Erbitux XRT + Cisplatin Overall survival/3y 77.9% 84.6% De-ESCALaTE Lancet. 2019;393:51-60 Results XRT + Erbitux XRT + Cisplatin Overall survival/2y 89.4% 97.5% So far, not clear you can substitute cisplatin with cetuximab
  107. 107. Virology Lectures 2019 Twenty-four lectures in virology, updated every year.
  108. 108. Cancer Information Cancer Videos Radiation Cancer Calculators Other Topics www.aboutcancer.com

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