2. Some facts………………………….
Squamous cell carcinoma of the head and neck
(SCCHN) is the sixth most common neoplasm in the
world today, with 500,000 cases expected each
year.
1/3
with only
of patients presenting with local
(stage I or II) disease, amenable to cure with
surgery or radiation in a high percentage of
patients.
2/3
Approximately
of patients present with
locally advanced disease, and are best treated
with multimodality approaches.
3. Numbers of cancer deaths due to
smoking in New Zealand in the year
2000 (and % for all cancer deaths)*
Type of cancer Men
Women
Total
Lung cancer 750 (87%) 430 (79%) 1180
ENT cancer** 127 (50%)
48 (49%) 175
Other cancer 274 (9%)
88 (3%) 362
All cancer
1151 (28%) 566 (16%) 1717
4. Men are more likely than women to
succumb to the disease by a ratio of 3:1.
The disparity between the sexes is
becoming less pronounced in the NZ.
Mortality rates are high at 54% overall.
Also, recurrence rates are high in the first
year following diagnosis of the primary
tumour, compared to many other cancers.
5. Warning Signs of Head and Neck Cancer
•
•
•
•
•
•
•
Hoarseness
•
Whitish lesion on tongue •
Referred otalgia
•
Persistent sore throat
•
Epistaxis
Nasal obstruction
Serous otitis media
Neck mass
Non-healing ulcer
Dysphagia
Submucosal mass
Not all cancers present with symptoms
at early stages!
6. Risk Factors for
Head and Neck Cancer
Tobacco Products:
Chemicals:
•
•
•
•
•
•
•
•
•
•
•
Smoking Tobacco
Cigarettes
Cigars
Pipes
Chewing Tobacco
Snuff
Ethanol Products
Asbestos
Chromium
Nickel
Arsenic
Formaldehyde
Other Factors:
• Ionizing Radiation
• Plummer-Vinson Syndrome
• Epstein-Barr Virus
• Human Papilloma Virus
7.
8.
9.
10. The global burden of oropharyngeal
SCC is estimated to be around 10%
(52 000 cases / annum) of all head and
neck SCCs (563 000 cases/annum).
11.
12.
13. The age-adjusted incidence of tonsillar
cancer increased 3·5-fold in women
and 2·6-fold in men between 1970
and 2002.
Augmented incidence of HPVassociated oropharyngeal cancers
represents an emerging viral epidemic
of cancer.
15. Epidemiology of HPV
•The most common STD worldwide
•80% sexually active adults in the US infected with at least
one HPV type by age 501
•Peak prevalence during adolescence and young adulthood
•Prevalence declines with age
•HPV 16 is the most common HR type
1. Centers for Disease Control and Prevention. Rockville, Md: CDC National
Prevention Information Network; 2004
16.
17. Human Papillomavirus (HPV)
• DNA virus
• Preferentially infect
squamous epithelial
cells
• >200 genotypes
• ≥40 genital HPV types
Prof. Zur Hausen
1976/1983/84
shared the 2008 Nobel Prize in Medicine with Luc
Montagnier and Françoise Barré-Sinoussi, who
discovered the HPV
19. Changing epidemiology
at least 15 types are thought to have oncogenic, most (>90%) HPVassociated HNSCC are caused by one virus type, HPV 16, the same
type that leads to HPV-associated anogenital cancers.
23. HPV-positive oropharyngeal cancer is associated with wild-type P53,
down-regulation of cyclin D and RB1,and upregulation of P16[cyclin
dependant kinase inhibitor]
24. HPV associated malignancy at the population level is a rare
event compared with frequency of infections in persons !
25.
26.
27. Why is increased incidence of
HPV-associated
oropharyngeal cancer most
pronounced in young
individuals?
28. People with serologic evidence of HPV-16
infection are 32 times more likely to develop
oropharyngeal cancer.
Those who had more than six oral sex partners
in their lifetime were 8.6 times more likely to
develop HPV-positive OPC.
• HPV prevalence in cervical rather
than penile tissue might boost the
chances of HPV infection when
performing oral sex on woman,
contributing to the higher rate of
HPV-associated oropharyngeal
cancer in men.
29. Many with HPV-positive disease have a
history of alcohol and tobacco use.
In fact, 10–30% of HPV-positive head
and neck squamous cell carcinomas
were recorded in heavy tobacco and
alcohol users.
32. P16 immunostaining of HNSCC is 100% sensitive but only 79% specifi c as a
surrogate marker of HPV infection.
ISH
33. In a cervical lymph node metastasis,
the presence of HPV reliably points
to the oropharynx as a likely site of
tumour origin.
a very useful application,
given that 13% of patients with
HNSCC present with a neck mass as
the first and only clinical
manifestation,
and 3% to 9% of the primary
tumours elude detection
34. How knowing HPV
status helps!
Some diagnostic
scenarios!!
detection of HPV in a
carcinoma that has
developed in the lung
after treatment of an
HPV related
oropharyngeal SCC can
confirm its metastatic
nature
35. • This cystic metastasis to a
cervical lymph node was
initially mistaken for a
branchial cleft cyst (H &
E).
• The presence of human
papillomavirus (HPV) in
the tumour cell nuclei
indicates tumour origin
from the oropharynx
(HPV type 16 in situ
hybridization).
36. • The presence of human
papillomavirus in this
small and inflamed
fragment of tonsillar
crypt epithelium helped
to establish its
neoplastic rather than
reactive nature (A: H &
E]
• B: HPV-type 16 in situ
hybridization).
• Arrows indicate dot-like
hybridization signals in
tumour cell nuclei.
38. Relevance of HPV status in
Oropharyngral SCC
*Need of molecular staging system is
compelling
*to better estimate the outcome
*inclusion criteria for vaccine based
trials
*for patient education
39.
40.
41. The biological explanation for improved
prognosis in HPV positive cases is uncertain !
• HPV-related tumours harbour fewer genetic
abnormalities –
• for example, chromosomal deletions and amplifications
• improved prognosis is related to incomplete
inactivation of p53.
• Younger / fitter patients have intact immune systems to
mount a host response against the tumour, and also
have fewer comorbidities, and are thus able to tolerate
more aggressive treatment regimens.
• Absence of field cancerization
• HPV-positive tumours tend to express low levels of
other biomarkers that correlate with poor prognosis in
locally advanced HNSCC, including the EGFR.
42. 226 Orophx
stage 3/4
RD Rx alone
70GY/35 f
3-Year survival
51% vs 31%
No change in
distant
metastasis
rate
RD Rx +
Carboplatin+5-fu
Results
maintained at 5
years
Disease Free
Survival
42% vs 20%
Significant toxicity
Dentition ,
myelosuppression,
NG tube feeding Etc
Bull Cancer 2000;
43. ECOG
2008
ISH for HPV and p16
Induction
Chemo[Carbo and
paclitaxel]+ RD Rx
HPV status correlated with treatment response, progression-free
survival, and overall survival and all outcomes were better in the
HPV-positive versus the HPV-negative population.
response rates to induction chemotherapy were 82% versus 55%
response at completion of chemoradiation was 84% versus 57%
progression-free survival at 2 years was 86% versus 53%
and overall survival at 2 years was 95% versus 62%
J Nat cancer inst 2008
44. Optimising the therapeutic ratio in
head and neck cancer
• Intensity of current Rx for advanced HN SCC is
in upper limit of human tolerance of acute
toxicities
• So we need to strike a balance !!
45.
46. De-escalation of Rx?
Why we are nervous?
• penalty of miscalculation is severe
• Too much de-escalation will lead to
more locoregional recurrences, some
of which might not be salvageable
• needs to be done in the controlled
environment of clinical trials.
53. Osteoradionecrosis
• Major complication of radiotherapy
• ORN of the mandible
• Intractable pain
• Trismus
• Nutritional deficiencies
• Loss of time from work and family
• Decreased QOL
57. Unanswered Questions !!
• Which exact sexual behaviours are associated
with transmission?
• How common is prevalent and persistent oral
HPV infection in the general population?
• Why is the increase in incidence of
oropharyngeal cancer Seen in men but not
women?
• Most apparent in younger cohorts?
• Should treatment of people with HPV-positive
and HPV negative head and neck squamous cell
carcinomas be different? ?
59. The common principles are:
Use of olive oil, Consumption of fresh fruits,
vegetables and legumes,
Moderate consumption of red meat, cheese and
yogurt 1 time a week fish or white meats 1 glass
of red wine to accompany the main meals
Drink at least 6 glasses of water a day
60.
61. The surgeon faces many dilemmas
when approaching the treatment of
the patient with head and neck cancer.
Not only are there numerous decisions
to take surrounding the surgical plan
but also the total care package will
include reference to wider issues
including the psychological status
of the patient
Schematic of HPV infection of a mucosal cell. After virion entry via endocytosis, the virus establishes a persistent infection as a viralepisome or integrates into the host genome. HPV E6 and E7 oncoproteins are expressed from both forms of the viral DNA, which lead top53 degradation and Rb inhibition, respectively. Methods of HPV, oncogene or p16 detection are depicted with respect to stage of HPVbiologic activity.
