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

1. Oropharynx Cancer 2019
Oropharyngeal cancer is the fastest-rising cancer among young white men
in the United States
aboutcancer.com

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. 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. Disease arising in the tonsillar
crypts in the lymphoid tissue
in the tonsils and base of the
tongue

5. 1. Epidemiology
2. Vaccination
3. Clinical Presentation
4. Treatment and Outcome
HPV and Oropharynx Cancer

7. 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

8. 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

9. 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

10. 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

11. 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.

12. 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

13. 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%

14. 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

15. 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

16. During the 60’s People became more ‘affectionate’

17. 1920 1940 1960 1980 2000
Year
smoking
H&N cancer
oropharynx
Other H&N
225% Increase in HPV+ vs 50% decrease in HPV -

18. 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 -

19. 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 -

20. 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

21. HPV Types

22. 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

23. 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.

24. Prevalence of high-risk oral HPV among adults aged 18–69, by
race and Hispanic origin and sex: United States, 2011–2014

25. 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%

26. 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

27. HPV Carcinogenic Mechanism

28. 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

30. 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

31. 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

32. Latency from Infection to Cancer
20 – 30 years

33. Projected Numbers of New Cases in the Future
J Clin Oncol
2011;29:4294

34. HPV-Associated Cancer Rates by State 2011–2015
Rates are per 100,000

35. 12,885 / 803 =
16 X
cdc.gov/cancer/hpv/statistics/
cases.htm

36. 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

37. 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

38. 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.

39. 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

40. Discussing the
diagnosis of HPV-
OSCC: Common
questions and
answers Fakhry ,
Gypsyamber
D’Souza.
Oral Oncology 49
(2013) 863–871

41. Tonsil
Base of
Tongue
Tonsil
Tonsil and Base
of Tongue, what
about other head
and neck sites?

42. 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.

43. 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)

44. 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;

45. 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)

46. 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

47. 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)

48. 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”

49. 1. Epidemiology
2. Vaccination
3. Clinical Presentation
4. Treatment and Outcome
HPV and Oropharynx Cancer

50. 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

51. www.cdc.gov/vaccines/schedules/index.html

52. 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

53. www.cdc.gov/vaccines/schedules/index.html

54. 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

55. 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.

56. 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

57. HPV Immunization 2017
Percent of 13-15 Vaccinated
Healthy People
2020 Target =
80%

58. 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

59. 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

60. 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.

62. 1. Epidemiology
2. Vaccination
3. Clinical Presentation
4. Treatment and Outcome
HPV and Oropharynx Cancer

63. Profile is young, white, male,
higher socioeconomic status
Asymptomatic
cervical adenopathy

65. 50 yo non-smoker, white male present with a lump in
his left neck and the PET scan as noted

66. 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).

67. 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

68. PET-CT = hot, cystic neck node and small lesion in tonsil
Path = squamous cancer, HPV +

69. 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

70. 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

71. Rate of New HPV-associated Oropharynx Cancer
in 2016

72. Oropharynx (base of tongue or
tonsil)

73. Typical smoking related oropharynx
cancer, presented with months of
throat pain radiating into ear

74. 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.

75. Oropharynx Symptoms
Based on HPV Status
HPV + HPV –
Neck mass (51%) Sore Throat (53%)
Sore Throat (28%) Dysphagia (41%)
Dysphagia (10%) Neck Mass (18%)

76. Typical Imaging for HPV Oropharynx Cancer
CT = large cystic node metastases PET = large neck mass with
small primary in tonsil

77. CT Scan Typical HPV + Patient
Large, Lobulated
neck mass of
lymph nodes
with no obvious
primary source
Neck biopsy =
squamous

78. Ultrasound Typical HPV + Patient
Large, Lobulated
neck mass of
lymph nodes
with no obvious
primary source

79. PET Scan Typical
HPV + Patient
Large lymph
node metastases
in the neck with
no obvious
primary source

80. Small cancer in
left base of
tongue
Large, necrotic lymph
node mass
Stage IVA Squamous
Cancer Left Base of
Tongue, HPV +

81. HPV Oropharynx Cancer
50 yo man, non-smoker presented with cystic neck
nodes and occult primary in the base of tongue

82. HPV Oropharynx Cancer
53 yo man
with large
cystic neck
node and
occult primary
in base of
tongue

83. 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)

84. HPV Tonsil Cancer

85. 1. Epidemiology
2. Vaccination
3. Clinical Presentation
4. Treatment and Outcome
HPV and Oropharynx Cancer

86. Survival for Tonsil Cancer
HPV +
HPV -

87. 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

88. 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

89. 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

90. 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

91. HPV and Survival with Oropharyngeal Cancer
N Engl J Med 2010; 363:24-35

92. 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

93. Most Patients are Treated with Chemo-Radiation
parotid parotid
Tonsil cancer
Lymph node met
Radiation field Radiation field

94. Chemoradiation for Tonsil Cancer

95. Chemoradiation for Base of Tongue

96. Chemoradiation
HPV +
HPV -
JCO September 20, 2010 vol. 28 no. 27 4142-4148

97. 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

98. 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

99. Considerable
toxicity from
combined
chemoradiation,
interest in ‘de-
escalation’ trials

100. 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

101. Survival with Oropharynx Cancer
Problem with the AJCC 7th ed staging system…it’s descriptive but not
prognostic for the HPV patients

102. 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?)

103. In 2017 (? 2018) Changes the Staging

104. 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

105. 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

106. Minimally Invasive Surgery
transoral laser surgery (TLM) transoral robotic surgery (TORS)

107. 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

108. 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

109. 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

110. 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

111. Virology Lectures 2019 Twenty-four
lectures in virology, updated every year.

112. Cancer Information
Cancer Videos
Radiation
Cancer Calculators
Other Topics
www.aboutcancer.com