Download Head and Neck cancers in young adults

4/11/2013
30th Alexandria International Combined ORL
Congress (10-12 April 2013)
Head and Neck cancers
in young adults
Wojciech Golusiński
Department of Head and Neck Surgery
The Great Poland Cancer Centre, Poznan, Poland
Poznan University of Medical Sciences, Poznan, Poland
Head and Neck cancer in young adults

DEFINITION

Epidemiology

Etiology

Diagnosis

Treatment

Conclusions
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Young adult – definition

Young patients have been defined as patients
under ages 35
35--40 years, with some studies
including those younger than 45.
10
20
30
40
50
60
70
80
Goldstein DP, Irish JC.
Head and neck squamous cell carcinoma in the young patient.
Curr Opin Otolaryngol Head Neck Surg. 2005 Aug; 13
13((4): 207
207--11
11..
University of Toronto, Department of OtolaryngologyOtolaryngology-Head and Neck Surgery/Surgical Oncology,
Wharton Head and Neck Program, Princess Margaret Hospital, Toronto, Ontario, Canada.
Young adult – definition

Young patients have been defined as people
under
u
de 40
0o
or 45
5 yea
years
so
of age, while
e tthe
e lower
o e limitt
of age is not defined at all or sometimes it is
defined as 15, 18 or 20 years.
10
20
30
40
50
60
70
80
Gawęcki W, Szyfter K, Szyfter W.
The role of exogenous and epidemiological factors in etiology
of squamous cell carcinoma of the head and neck in young adults.
Otolaryngol Pol 2007; 61 (1): 52
52--57
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Young adults

GROUP 1:
patients under age 35 years, with a female
predominance,, few behavioral risk factors
predominance
and pathologically more aggressive cancers.

GROUP 2:
patients under age 40 with a male predominance,
predominance,
extensive
t
i ttobacco
b
and
d alcohol
l h l abuse,
abuse
b
, who
h presentt
with advanced cancer and a prognosis dependent
upon presenting stage.
Funk GF, Karnell LH, Robinson RA, et al.
Presentation, treatment and outcome of oral cavity cancer:: a National Cancer Data Base report.
Head Neck 2002;
2002; 24
24:: 165165-180
Young adults

GROUP 3:
patients under age 40 with a slight male
predominance,, roughly half have a history of tobacco
predominance
use.
Predominance of earlyearly-stage and wellwell-differentiated
cancers as well as better or equivalent response to
treatment to that seen in older patients with similar
stage disease are noticed.
Funk GF, Karnell LH, Robinson RA, et al.
Presentation, treatment and outcome of oral cavity cancer:: a National Cancer Data Base report.
Head Neck 2002; 24: 165165-180
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Head and Neck cancer in young adults

Definition

EPIDEMIOLOGY

Etiology

Diagnosis

Treatment

Conclusions
Epidemiology

A trend for an increasing percentage of younger patients in
head and neck squamous cell carcinoma has been noticed
in the US
US, various European countries and China since
1970.
Indian J Public Health.
Risk for oral cancer associated to smoking, smokeless and oral dip products.
2012 Jan-Mar;56(1):57-60.
Genden EM, Sambur IM, de Almeida JR, Posner M, Rinaldo A, Rodrigo JP, et al.
Human papillomavirus and oropharyngeal squamous cell carcinoma: what the clinician should know.
Eur Arch Otorhinolaryngol 2013; 270: 405-16.
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Epidemiology

In the Indian subsub-continent, where there is a much higher
overall rate of head and neck squamous cell carcinoma,
a similar trend is occurr
occurring.
Sinha R, Daniel CR, Devasenapathy N, Shetty H, Yurgalevitch S, Ferrucci LM, et al. Multi-center
feasibility study evaluating recruitment, variability in risk factors and biomarkers for a diet and cancer
cohort in India. BMC Public Health 2011; 11: 405.
Epidemiology
Cancer incidence by age
200
Inherited
predisposition
Incid
dence rate per 100
100,,00
00
180
160
140
120
100
80
60
40
20
0
10
20
30
40
50
60
70
80
9th International Netherlands Cancer Institute Head and Neck Symposium,
Amsterdam, the Netherlands, 1616-17 April, 2009
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4/11/2013
Epidemiology

11.3% of all oral cavity and oropharynx cancers and
4,5% of larynx cancers occur in patients under
age 45 years.
Grulich AE, Jin F, Conway EL, Stein AN, Hocking J.
Cancers attributable to human papillomavirus infection. Sex Health 2010; 7: 244-52.
Genden EM, Sambur IM, de Almeida JR, Posner M, Rinaldo A, Rodrigo JP, et al. Human papillomavirus
and oropharyngeal squamous cell carcinoma: what the clinician should know. Eur Arch Otorhinolaryngol
2013; 270: 405-16.
Epidemiology

The oral cavity is the most common site for head and neck
squamous cell carcinoma in young patients,
with the tongue being the most common subsite.

Oropharyngeal cancer also accounts for a higher
percentage of head and neck squamous cell carcinoma
in young patients compared with older patients.
Early stage squamous cell cancer of the oral tongue--clinicopathologic features affecting outcome.
Cancer, 2012
Trends in incidence of oral and pharyngeal carcinoma in Florida: 1981–2008, Public Health Dent, 2012
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Epidemiology
DEMOGRAPHICS OF YOUNG PATIENTS
SITE
- Oral Cavity (usually OT) 4040-45
45%
%
 Site: OC 44%,
- Oropharynx 20
20--30
30%
%
- Larynx/HP 20
20--40
40%
%
salivary gland 23%,
- Missclassification of BOT as "tongue"
nasopharynx 44%,
- Variation for older cohorts & those with high smoking
larynx 10%,
prevalence
M:F ratio
oropharynx 5%,
- Oral Cavity - females~males
hypopharynx 1%
- Oropharynx - males>females
- Larynx
y - males>
males>femase
femase
Soudry
S d E,
E Preis
P i M,
M Hod
H d R,
R Hamzany
H
Y Hadar
Y,
H d T,
T
Smoking
Bahar G, et al. Squamous cell carcinoma of the
- Oral Cavity - 4040-60
60%
% never
oral tongue in patients younger than 30 years:
years:
clinicopathologic
- Oropharynx - dependent on period of cohort
features and outcome.
outcome. Clin Otolaryngol 2010
2010;;
- Larynx - typical (except children/adolescents)
35:: 307
35
307--12
12..
9th International Netherlands Cancer Institute
Head and Neck Symposium,
Symposium,
Amsterdam, the Netherlands
Netherlands,, 16
16--17 April,
April, 2009
Epidemiology
Site Distribution by Age Category
(2042 incident patients)
No.=102
364
1270
306
100%
Oral Cavity Females
75%
Oral Cavity Males
Oropharynx Females
50%
Oropharynx Males
25%
Larynx/HP Females
0%
Larynx/HP Males
<40 yrs
40-49 yrs
50-69 yrs
70+ yrs
9th International Netherlands Cancer Institute Head and Neck Symposium,
Amsterdam, the Netherlands, 1616-17 April, 2009
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4/11/2013
Head and Neck cancer in young adults

Definition

Epidemiology

ETIOLOGY

Diagnosis

Treatment

Conclusions
Etiology
Head and Neck Cancer in the Young
Potential Etiologic Associations

Smoking

Alcohol

Other Tobacco Products

Second--Hand Smoke?
Second

Asbestos?

Acid Reflux?

Nutrition?

Marijuana?

HPV?

Genetics?
9th International Netherlands Cancer Institute Head and Neck Symposium,
Amsterdam, the Netherlands, 1616-17 April, 2009
8
4/11/2013
Etiology

Tobacco and alcohol have long been implicated as the
traditional risk factors for head and neck squamous cell
carcinoma in adults at any age.

Contrary to older patients, many of the younger patients
with oral squamous cell carcinoma have declared never
y
to have smoked or consumed alcohol excessively.
Islami F, Fedirko V, Tramacere I, Bagnardi V, Jenab M, Scotti L, et al.Alcohol drinking and esophageal
squamous cell carcinoma with focus on light-drinkers and never-smokers:
a systemic review and meta-analysis. Int J Cancer 2011; 129: 2473-84.
Etiology

It has been suggested that exposure to carcinogens such
as alcohol and tobacco might be of too short a duration
for malignant transformation to occur in younger patients.
Islami F, Fedirko V, Tramacere I, Bagnardi V, Jenab M, Scotti L, et al.
al.Alcohol drinking and
esophageal squamous cell carcinoma with focus on lightlight-drinkers and nevernever-smokers:
smokers:
a systemic review and metameta-analysis
analysis.. Int J Cancer 2011; 129: 24732473-84.
Toner M, O'Regan EM.
EM. Head and neck squamous cell carcinoma in the young: a spectrum or a
distinct group? Part 1. Head Neck Pathol 2009; 3: 246
246--8.
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Etiology

In the UK, Llewellyn indicates many young patients
are heavy smokers and drinkers and although the exposure
time still seems short, some have had 20+ years of
smoking by their early forties.
Llewellyn CD, Linklater K, Bell J, et al.
An analysis of risk factors for oral cancer in young people: a case control study.
Oral Oncol. 2004
2004;; 40(
40(3): 304
304--13
13..
Etiology

It appears that many in the 4040-45 age group have
traditional risk factor exposure and represent the tail end
of the more usual patient group, whereas patients under
40 years of age are more likely to be nonnon-smokers.
Toner M, O’Regan EM.
Head and Neck Squamous Cell Carcinoma in the Young: A Spectrum or a Distinct Group?
Head Neck Pathol 2009; 3: 246
246--248.
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Etiology

30% of the young patients claimed not to have used
tobacco compared with only 9% of the older patients
patients.
Goldenberg D, Brooksby C, Hollenbeak CS. Age as a determinant of outcomes for patients with
oral cancer. Oral Oncol 2009; 45: e57
e57--61.

In the West smokeless tobacco has not emerged
as a significant factor in young patients
patients.
Toner M, O’Regan EM.
Head and Neck Squamous Cell Carcinoma in the Young: A Spectrum or a Distinct Group?
Head Neck Pathol 2009; 3: 246
246--248.
Etiology

Further epidemiological studies are necessary to determine
whether marijuana smoking can cause oral premalignant
lesions and cancer, possibly due to field cancerization
of the upper aerodigestive tract.
Liang C, McClean MD, Marsit C, Christensen B, Peters E, Nelson HH, et al. A population-based casecontrol study of marijuana use and head and neck squamous cell carcinoma.
Cancer Prev Res (Phila) 2009; 2: 759-68.
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Etiology

Herpes simplex virus, Epstein
Epstein--Barr virus and human
papilloma virus have been investigated as causes of head
and neck squamous cell carcinoma in young patients.
An association has been found between HPVHPV-16
and the development of oropharyngeal carcinoma,
specifically for cancers of the palatine and lingual tonsilis.
Genden EM, Sambur IM, de Almeida JR, Posner M, Rinaldo A, Rodrigo JP, et al. Human papillomavirus
and oropharyngeal squamous cell carcinoma: what the clinician should know. Eur Arch Otorhinolaryngol
2013; 270: 405-16.
Etiology
HPV-16 in Tumors
HPV16 Tumor Status
Site
E6+
E7+
Either +
Oral Cavity
(No.=256)
46 (18.0%)
38 (14.8%)
53 (20.7%)
Oropharynx
(No.=217)
173 (79.7%)
170 (78.3%)
179 (82.5%)
9th International Netherlands Cancer Institute Head and Neck Symposium,
Amsterdam, the Netherlands, 1616-17 April, 2009
12
4/11/2013
Etiology
Oropharyngeal Cancer Patients
(Segregated by Age, HPV16, &Smoking)
50%
40%
HPV16 PCR+ NonSmk
mean age=51.4
30%
HPV16 PCR+ Smk
mean age=56.2
20%
HPV16 PCRnegative
HPV16
mean age=56
age=56..7
10%
0%
<50 years
50-59 years
>59 years
9th International Netherlands Cancer Institute Head and Neck Symposium,
Amsterdam, the Netherlands, 1616-17 April, 2009
Etiology

It has been shown that patients younger than 30 years
g
y increased chromosome fragility
g y
exhibited a significantly
compared to older patients following mutagen exposure.
In addition a higher frequency of microsatellite instability
has been found in younger patients.

Conversely, no significant differences were found in the
expression of p53, p21, Rb and MDM2 proteins between
patients younger than 35 years and older than 75 years.
Goldstein D.P., Irish J.C.
Squamous cell carcinoma in the young.
Curr.. Opin
Curr
Opin.. Otolaryngol
Otolaryngol.. Head Neck Surg. 2005; 13, 207
207--211
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Etiology

The principal findings in molecular studies of young
patients with HNSCC ((nonsmokers)) is that HNSCC
p
developing in these patients is markedly different,
not in any recognizable phenotypic way, but undoubtedly
at a genetic level.
Toner M
M., O
O’Regan
Regan E.M.
EM
Head and Neck Squamous Cell Carcinoma in the Young: A Spectrum or a Distinct Group? Part 2.
Head Neck Pathol 2009
2009;; 3: 249
249--251.
Etiology
Proposal of an integrated model of molecular
carcinogenesis for head and neck squamous cell
carcinoma according to Leemans CR.
Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer.
Nat Rev Cancer 2011;
2011; 11:
11: 9-22
22..
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Etiology
Etiology of Malignancies of the Head & Neck Region
nasopharynx
9th International Netherlands Cancer Institute Head and Neck Symposium,
Symposium,
Amsterdam, the Netherlands
Netherlands,, 1616-17 April,
April, 2009
Head and Neck cancer in young adults

Definition

Epidemiology

Etiology

DIAGNOSIS

Treatment

Conclusions
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Diagnosis

There are NO SIGNIFICANT DIFFERENCES
process of the diagnosis
g
of head and neck squamous
q
in the p
cell carcinoma in young adults comparing to the group
of older patients.
Clinicopathologic features and outcomes

Compared to the older group, the younger patients have
a significantly worse clinical/radiological N stage in
presentation (therefore a more advanced tumour stage:
73%
73
% stage 3-4) and more evidence of perineural invasion
on histopathological examination.
Soudry E, Preis M, Hod R, Hamzany Y, Hadar T, Bahar G, et al. Squamous cell carcinoma of the oral
tongue in patients younger than 30 years: clinicopathologic features and outcome. Clin Otolaryngol 2010;
35: 307-12.
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Clinicopathologic features and outcomes

Above mentioned differences between young and adult
patients may
p
y be explained
p
by
y a delay
y in diagnosis
g
owing
g to
a lower index of clinical suspicion of tongue squamous cell
carcinoma in younger patients or a more aggressive ageagerelated biologic behaviour of the tumour.

The latter assumption is supported by the significantly
higher rate of perineural invasion on histopathological
examination in younger group.
Clinicopathologic features and outcomes

Perineural invasion has been shown to be associated with
g risk of regional
g
metastases,, local recurrence and
a high
decreased survival. At the same time second head and
neck primary tumours develope only in the older patients.
These results may suggest that tumour biology might be
age--related.
age
Curado MP, Hashibe M. Recent changes in the epidemiology of head and neck cancer.
Curr Opin Oncol 2009; 21: 194-200.
Soudry E, Preis M, Hod R, Hamzany Y, Hadar T, Bahar G, et al. Squamous cell carcinoma of the oral
tongue in patients younger than 30 years: clinicopathologic features and outcome. Clin Otolaryngol 2010;
35: 307-12
17
4/11/2013
Head and Neck cancer in young adults

Definition

Epidemiology

Etiology

Diagnosis

TREATMENT

Conclusions
Treatment

When pertinent differences in stage, grade and treatment
between young patients group and adult patients group are
controlled for, outcomes are identical, suggesting that
young patients should receive the same therapy that is the
standard of care for adult patients.
Morris LGT
LGT,, Patel SG,
SG, Shah JP,
JP, Ganly I.
Squamous cell carcinoma of the oral tongue in the pediatric age group: a matchedmatched-pair analysis
of survival.
Arch Otolaryngol Head Neck Surg 2010
2010;; 136 (No 7) July
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Treatment

Traditionally patients with head and neck squamous cell
carcinoma are treated with surgical resection and, when
indicated postoperative adjuvant radiotherapy
indicated,
radiotherapy.
However such treatment can be functionally debilitating,
and radiotherapy may subject the young patient to years
of longlong-term adverse sequelae.
sequelae.
Sturgis EM, Moore BA, Glisson BS, Kies MS, Shin DM, Byers RM
Neoadjuvant chemotherapy for squamous cell carcinoma of the oral tongue
in young adults: a case series.
Head Neck 2005
Zhen Y, Wang JG, Tao D, Wang HJ, Chen WL.
Efficacy survey of swallowing function and quality of life in response to therapeutic intervention following
rehabilitation treatment in dysphagic tongue cancer patients. Eur J Oncol Nurs 2012; 16: 54-8.
Treatment

American Society of Clinical Oncology (ASCO) 2012 annual
meeting:
neoadjuvant chemotherapy - no survival advantage
Haddad I. R et al. The PARADIGM trial: A phase III study comparing sequential therapy (ST) to concurrent
chemoradiotherapy (CRT) in locally advanced head and neck cancer (LANHC). J Clin Oncol (Meeting
Abstracts) 2012; 30: 5501
Ezra E et al. De CIDE: A phase III randomized trial of docetaxel (D), cisplatin (P), 5-fluorouracil (F) (TPF)
induction chemotherapy (IC) in patients with N2/N3 locally advanced squamous cell carcinoma of head
and neck (SCCHN). J Clin Oncol (Meeting Abstracts) 2012; 30: 5500
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Treatment

Despite encouranging findings according neoadjuvant
py, it is maintained that the standard treatment
chemotherapy,
of oral tongue cancer in the young adult should remain
surgery with adjuvant radiotherapy determined
by the surgical pathology results.
Sturgis EM
EM,, Moore BA,
BA, Glisson BS,
BS, Kies MS,
MS, Shin DM,
DM, Byers RM
Neoadjuvant chemotherapy for squamous cell carcinoma of the oral tongue
in young adults: a case series.
Head Neck 2005
Head and Neck cancer in young adults

Definition

Epidemiology

Etiology

Diagnosis

Treatment

CONCLUSIONS
20
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Conclusions

Young adults are the group of patients with increased
y important
p
not
incidence of Head and Neck cancer ((very
only for ENT but also for general practitioner!).

The higher incidence of nonsmokers, lower gender ratio,
a greater percentage of oral cavity and otopharynx tumors
and lower incidence of second primaries suggest the
possibility of different etiologic factors in the younger patient
group. Further investigations into genetic factors may yield
further insight.
David P. Goldstein
Conclusions

Remember about the HPV16 infection in young adults with
p y g
cancer.
oral and oropharyngeal

During the diagnosis of Head and Neck cancer in young
adults especially such features like perineural or vascular
invasion should be estimated.

Do not forget about the patients’
patients age and future quality
of their life when planning the treatment procedures.

Future
?
21