1. Head and Neck Squamous Cell Carcinoma (HNSCC)
Medical Education
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2. HNSCC epidemiology HNSCC, head and neck squamous cell carcinoma.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).

3. What is head and neck cancer?
Head and neck cancer is the term used to describe a wide range of tumours originating in the upper airway and swallowing tract (e.g. lip, oral cavity, tongue, throat and voice box)1
Despite the variety in location of head and neck cancers, they are mostly of the same cell type,1 with 90% being HNSCC2
HNSCC is a heterogeneous disease with multiple aetiologies, resulting in distinct molecular subsets of tumours with different biological and clinical characteristics3
Notes Header
1.Stewart BW and Wild CP (eds). World Cancer Report. Lyon: WHO IARC Press, pp. 423.
2. Ferrarotto R and Gold K A. Afatinib in the treatment of head and neck squamous cell carcinoma. Expert Opin Investig Drugs ;23(1):135–143.
3. Mountzio G, Rampias T, Psyrri A. The mutational spectrum of squamous cell carcinoma of the head and neck:targetable genetic events and clinical impact. Annals of Oncol 2014;25(10):1889–1900
HNSCC, head and neck squamous cell carcinoma.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Stewart BW and Wild CP (eds). World Cancer Report. Lyon: WHO IARC Press, pp. 423; 2. Ferrarotto R, Gold K A. Expert Opin Investig Drugs 2014;23(1):135–43; 3. Mountzio G, et al Ann Oncol 2014;25(10):1889–900; Image from:

4. Global incidence of head and neck cancer
Worldwide, head and neck cancer accounts for more than 550,000 cases annually1
In the US, approximately 62,000 Americans develop head and neck cancer annually2
In Europe, there were approximately 140,000 cases in 20123
Nasopharyngeal cancer is endemic in South East Asia5
Mouth and tongue cancers are the most prevalent cancer type in Indian men4
1.Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Allen C, et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol 2016.
2.Siegel RL, Miller KD, Jemal A. Cancer Statistics, CA Cancer J Clin 2017; 67:7.
3. Gatta G, Botta L, Sanchez MJ, et al. Prognoses and improvement for head and neck cancers diagnosed in Europe in early 2000s: The EUROCARE-5 population-based study. Eur J Cancer 2015; 51:2130.
4. Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in Int J Cancer ; 132:1133.
5. Adham et al Chin J Cancer; 2012; Vol. 31 Issue 4
HNSCC, head and neck squamous cell carcinoma.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Head and neck cancer. Union for International Cancer Control 2014 Review of Cancer Medicines on the WHO List of Essential Medicines. (Accessed: March 2017); 2. Siegel RL, et al. Cancer Statistics, CA Cancer J Clin 2017;67:7; 3. Gatta G, et al. Eur J Cancer 2015; 51:2130; 4. Bray F, et al. Int J Cancer 2013;132:1133; 5. Lambert R et al. Eur J Gastroenterol Hepatol 2011;23:633.

5. Older males are more commonly affected by HNSCC
Males are affected significantly more than females with a ratio ranging from 2:1 to 4:11
The incidence in males exceeds 20 per 100,000 in regions of France, Hong Kong, the Indian subcontinent, central and eastern Europe, Spain, Italy, Brazil, and among African Americans in the US2
The risk of contracting HNSCC increases with age. The majority of cases occur in people of over 50 years of age, and it is more common in men3
The incidence of laryngeal cancer, but not oral cavity and pharyngeal cancer, is approximately 1.6 times higher in African American men4
1.Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Allen C, et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol 2016.
2.Siegel RL, Miller KD, Jemal A. Cancer Statistics, CA Cancer J Clin 2017; 67:7.
3. Gatta G, Botta L, Sanchez MJ, et al. Prognoses and improvement for head and neck cancers diagnosed in Europe in early 2000s: The EUROCARE-5 population-based study. Eur J Cancer 2015; 51:2130.
4. Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in Int J Cancer ; 132:1133.
5. Lambert R, Sauvaget C, de Camargo Cancela M, Sankaranarayanan R. Epidemiology of cancer from the oral cavity and oropharynx. Eur J Gastroenterol Hepatol 2011; 23:633.
6. Genetics Home Reference website. Head and neck squamous cell carcinoma. Available at: neck-squamous-cell-carcinoma (Accessed June 2016).
7. DeSantis C, Naishadham D, Jemal A. Cancer statistics for African Americans, CA Cancer J Clin 2013; 63:151.
4. Union for International Cancer Control. Head and neck cancer Review of Cancer Medicines on the WHO list of essential medicines (Accessed June 2016).
HNSCC, head and neck squamous cell carcinoma.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Head and neck cancer. Union for International Cancer Control 2014 Review of Cancer Medicines on the WHO List of Essential Medicines. (Accessed: March 2017); 2. Forman et al ,Vol x, IARC Scientific Publications 164; 3. Vigneswaran et al Oral Maxillofac Surg Clin North Am 2014;26(2):123–41; 4. De Santis et al CA Cancer J Clin 2013;63:151–66.

6. Global mortality caused by HNSCC
Prognosis for patients with recurrent/metastatic HNSCC is very poor, and despite ongoing efforts to develop new therapy options, treatment of this type of cancer remains challenging1
300,000 deaths are caused by HNSCC each year2
13,000 deaths in the US3 and 63,500 deaths in Europe in 20124
The mortality associated with both laryngeal and oropharyngeal cancer is significantly higher in African American men, which may reflect the lower prevalence of HPV positivity in this population5
Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Allen C, et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life- years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol 2016.
Siegel RL, Miller KD, Jemal A. Cancer Statistics, CA Cancer J Clin 2017; 67:7.
Gatta G, Botta L, Sanchez MJ, et al. Prognoses and improvement for head and neck cancers diagnosed in Europe in early 2000s: The EUROCARE-5 population-based study. Eur J Cancer 2015; 51:2130.
HNSCC, head and neck squamous cell carcinoma; HPV, human papillomavirus.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Machiels JP, et al. BMC Cancer 2014;14:473; 2. Head and neck cancer. Union for International Cancer Control 2014 Review of Cancer Medicines on the WHO List of Essential Medicines Siegel RL, et al. CA Cancer J Clin 2017;67(1):7; 4. Gatta G, et al. Eur J Cancer 2015;51:2130; 5. Settle K, et al. Cancer Prev Res 2009;2(9)776–81.

7. 5-year survival rates1
5-year survival has improved for head and neck cancer patients over the past twenty years, and is currently around 66%
The greatest improvement was seen in tonsillar and tongue cancers
% patients surviving for 5 years:
Location
1982–1986 PE (SE)
1987–1991 PE (SE)
1992–1996 PE (SE)
1997–2001 PE (SE)
PE (SE)
Difference*
p-value
All
52.7 (0.5)
53.2 (0.5)
54.7 (0.5)
58.6 (0.5)
65.9 (0.5)
+11.2
<0.0001
Lip
92.5 (1.3)
95.6 (1.4)
95.5 (1.4)
90.9 (1.5)
97.4 (1.7)
+1.9
0.5
Tongue
45.2 (1.2)
48.1 (1.2)
50.5 (1.2)
55.6 (1.1)
64.9 (1.0)
+14.4
Oral cavity
53.6 (1.0)
52.6 (1.0)
51.1 (1.0)
56.6 (1.1)
62.9 (1.2)
+11.8
Nasopharynx
47.1 (2.2)
47.6 (2.1)
53.8 (2.1)
58.3 (1.9)
62.3 (1.9)
+8.3
0.002
Tonsil
39.7 (1.7)
41.8 (1.7)
47.6 (1.7)
56.5 (1.5)
69.8 (1.3)
+22.2
Oropharynx
26.2 (2.9)
23.4 (2.6)
33.3 (3.2)
37.8 (3.1)
42.2 (3.1)
+8.9
0.2
Hypopharynx
24.2 (1.4)
26.2 (1.5)
29.8 (1.6)
29.7 (1.6)
33.8 (2.0)
+4.0
0.3
Larynx
66.8 (0.8)
66.3 (0.8)
64.9 (0.9)
64.3 (0.9)
66.8 (0.9)
*Difference between values in 1992–1996 and those in p-value stated is for comparison of trend between1992–1996 and 2002– PE, point estimate; SE, standard error.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Pulte D, Brunner, H. Oncologist 2010;15(9):994–1001.

8. Prognosis in HNSCC
5-year relative survival rate improved from 52.7% to 65.9% between –1986 and 2002–2006 in all head and neck cancers1
The exceptions to this trend were lip, oropharyngeal and hypopharyngeal cancer
However, there has been little improvement since then: recent SEER statistics indicate that 5-year survival is 64% in patients with oral cavity and pharynx cancer, and 61% in patients with laryngeal cancer (data from period 2006–2012)2
Better prognosis for HPV-associated HNSCC3
HPV and p16 detection are established markers for HPV-related HNSCC
Both are accepted as predictors of survival
Survival of patients with HNSCC is prolonged if disease is HPV(+)/p16(+) or HPV(–)/p16(+)
HNSCC, head and neck squamous cell carcinoma, HPV, human papillomavirus; PE, point estimate; SE, standard error; SEER, Surveillance, Epidemiology, and End Results Program.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Pulte D, Brunner, H. Oncologist 2010;15(9):994–1001; 2. SEER Cancer Statistics. and (Accessed: March 2017); 3. Coordes A, et al. Eur Arch Otorhinolaryngol 2016;273(8):

9. HNSCC risk factors HNSCC, head and neck squamous cell carcinoma.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).

10. Main risk factors for head and neck cancers
Lifestyle risk factors account for the development of approximately 80% of cases of head and neck cancer1
HPV and EBV are also known risk factors2
Variations in prevalence of these risk factors contribute to geographical differences in the observed distribution of head and neck cancer3
Tobacco use
Alcohol consumption
HPV infection (for oropharyngeal cancer)
EBV infection (for nasopharyngeal cancer)
1.Stewart BW and Wild CP (eds). World Cancer Report. Lyon: WHO IARC Press, pp. 423.
2. Lubin JH, Purdue M, Kelsey K, et al. Total exposure and exposure rate effects for alcohol and smoking and risk of head and neck cancer: a pooled analysis of case-control studies. Am J Epidemiol Oct 15;170(8):937–047.
EBV, Epstein-Barr virus; HVP, human papillomavirus.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Stewart BW and Wild CP (eds). World Cancer Report. Lyon: WHO IARC Press, pp. 423; 2. Deng Z, et al. PLoS One 2014;9(11):e113702; 3. Lubin JH, et al. Am J Epidemiol 2009;15;170(8):937–047.

11. Tobacco and alcohol are key risk factors for HNSCC
Heavy smokers have an increased risk of HNSCC compared with nonsmokers1
Cigar and pipe smoking are associated with an increased incidence of head and neck cancer that is independent of cigarette use1
Smokeless tobacco (both chewing tobacco and snuff) is associated with an increased risk of cancer of the oral cavity and pharynx2
Chewing betel nuts and paan are also considered risk factors3
Tobacco
Alcohol consumption independently increases the risk of HNSCC4
The risk may be multiplied by the interactive effects of alcohol intake and tobacco consumption5
Genetic polymorphisms of alcohol dehydrogenase and aldehyde dehydrogenase may increase the risks associated with alcohol consumption6
Alcohol
1.Wyss A, Hashibe M, Chuang SC, et al. Cigarette, cigar, and pipe smoking and the risk of head and neck cancers: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Am J Epidemiol 2013; 178:679.
2. Blot WJ, McLaughlin JK, Winn DM, et al. Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res 1988; 48:3282.
3. Spitz MR. Epidemiology and risk factors for head and neck cancer. Semin Oncol 1994; 21:281.
4. Proia NK, Paszkiewicz GM, Nasca MA, et al. Smoking and smokeless tobacco-associated human buccal cell mutations and their association with oral cancer--a review. Cancer Epidemiol Biomarkers Prev 2006; 15:1061.
5. Sapkota A, Gajalakshmi V, Jetly DH, et al. Smokeless tobacco and increased risk of hypopharyngeal and laryngeal cancers: a multicentric case-control study from India. Int J Cancer 2007; 121:1793.
6. Rosenquist K, Wennerberg J, Schildt EB, et al. Use of Swedish moist snuff, smoking and alcohol consumption in the aetiology of oral and oropharyngeal squamous cell carcinoma. A population- based case-control study in southern Sweden. Acta Otolaryngol 2005; 125:991.
7. Znaor A, Brennan P, Gajalakshmi V, et al. Independent and combined effects of tobacco smoking, chewing and alcohol drinking on the risk of oral, pharyngeal and esophageal cancers in Indian men. Int J Cancer 2003; 105:681.
8. Druesne-Pecollo N, Tehard B, Mallet Y, et al. Alcohol and genetic polymorphisms: effect on risk of alcohol-related cancer. Lancet Oncol ; 10:173.
HNSCC, head and neck squamous cell carcinoma.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Wyss A, et al. Am J Epidemiol 2013;178: Proia NK, et al. Cancer Epidemiol Biomarkers Prev 2006;15:1061; 3. Dasgupta S, et al. J Cell Physiol. 2012;227:467–73; 4. Freedman ND, et al. Br J Cancer 2007;96,1469–74; 5. Znaor A, et al. Int J Cancer 2003;105:681; 6. Druesne-Pecollo N, et al. Lancet Oncol 2009;10:173.

12. HPV is a risk factor for HNSCC
Infection with HPV, a common, sexually transmitted virus, is associated with oropharyngeal cancers1
At least one of two viral oncogenes (E6 and E7) are necessary to maintain cell immortalisation and the malignant phenotype1
By 2030, over half of head and neck cancers will be related to HPV2
An increased incidence of HPV-associated oropharyngeal cancer has been observed in white middle-aged men2
The HPV-16 genotype has been identified as the causative agent in approximately 45–90% of HNSCC cases3
Other high-risk HPV genotypes, such as HPV-18, -31, -33 or -35, are also causative but are less common4
zur Hausen H. J Natl Cancer Inst 2000; 92:690.
O'Sullivan B, Huang SH, Su J, et al. Lancet Oncol 2016; 17:440.
Chaturvedi AK, Anderson WF, Lortet-Tieulent J, et al. J Clin Oncol ; 31:4550.
Vokes EE, Agrawal N, Seiwert TY. J Natl Cancer Inst 2015; 107:djv344.
Weinberger PM, Yu Z, Haffty BG, et al. J Clin Oncol 2006; 24:736.
HPV-positive tumours are associated with better prognosis than HPV-negative HNSCC tumours and so testing for HPV status may be useful as a prognostic marker5
HNSCC, head and neck squamous cell carcinoma; HVP, human papillomavirus.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. zur Hausen H. J Natl Cancer Inst 2000;92:690–8; 2. Pytynia et al Oral Oncol 2014;50(5):380–86; 3. D’Souza et al Prev Med 2011;53(Suppl. 1):S5–S11; 4. Spence T, et al Cancers 2016;8:75; doi: /cancers ; 5.. Weinberger PM, et al. J Clin Oncol 2006;24:736.

13. HNSCC clinical staging
HNSCC, head and neck squamous cell carcinoma.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).

14. HNSCC categorisation by location
Head and neck cancer is categorised by the area of the head or neck in which it occurs
Sites include:
Larynx
Oral cavity, including the tongue
Oropharynx, including the base of the tongue and tonsils
Nasopharynx
Notes Header
First level bullet
Second level bullet
Third level bullet
Fourth level bullet
HNSCC, head and neck squamous cell carcinoma.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Head and neck cancer fact sheet. (Accessed: March 2017).

15. Staging of HNSCC (T)1 Stage Example (oral cavity) TX
Staging is essential to the proper and successful management of HNSCC
HNSCC is staged according to the Tumour – Node – Metastasis (TNM) system
T (Tumour) staging is described below
Stage
Example (oral cavity) TX
Primary tumour cannot be assessed T0
No evidence of primary tumour
Tis
Carcinoma in situ T1
≤2 cm T2
>2 cm to 4 cm T3
>4 cm
T4a
Through cortical bond, deep/extrinsic muscle of tongue, maxillary sinus and skin
T4b
Masticator space, pterygoid plates, skull base and internal carotid artery
1. Deschler DG, Moore MG, Smith RV, eds. Quick Reference Guide to TNM Staging of Head and Neck Cancer and Neck Dissection Classification, 4th ed. Alexandria, VA: American Academy of Otolaryngology–Head and Neck Surgery Foundation, 2014.
2. Diagnosis and management of head and neck cancer, a national guideline. October Available at: (Accessed June 2016).
HNSCC, head and neck squamous cell carcinoma; T, tumour.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Deschler DG, Moore MG, Smith RV, eds. Quick Reference Guide to TNM Staging of Head and Neck Cancer and Neck Dissection Classification, 4th ed. Alexandria, VA: American Academy of Otolaryngology–Head and Neck Surgery Foundation, 2014.

16. Staging of HNSCC (N and M)1
Definitions of N (regional lymph nodes) and M (metastases) are shown below NX
Regional lymph nodes cannot be assessed N0
No regional lymph nodes metastases N1
Ipsilateral single ≤3 cm N2
a. Ipsilateral single >3 up to 6 cm
b. Ipsilateral multiple ≤6 cm
c. Bilateral, contralateral ≤6 cm N3
>6 cm MX
Distant metastasis cannot be assessed M0
No distant metastasis M1
Distant metastasis
HNSCC, head and neck squamous cell carcinoma; M, metastases; N, nodes.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Deschler DG, Moore MG, Smith RV, eds. Quick Reference Guide to TNM Staging of Head and Neck Cancer and Neck Dissection Classification, 4th ed. Alexandria, VA: American Academy of Otolaryngology–Head and Neck Surgery Foundation, 2014.

17. Staging of HNSCC: Permutations of TNM staging1
Stage 0 T N M
Stage I T1 N0 M0
Stage II T2
Stage III T3
T1,T2,T3 N1
Stage IVA
T1, T2, T3 N2
T4a
N0, N1, N2
Stage IVB Tb
Any N
Any T N3
Stage IVC M1
HNSCC, head and neck squamous cell carcinoma; M, metastases; N, node; T, tumour.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Gregoire V, et al. Ann Oncol 2010;21(Suppl. 5):v184–v186.

18. Diagnostic work-up of HNSCC
HNSCC, head and neck squamous cell carcinoma.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).

19. Common signs and symptoms of head and neck cancer
Signs and symptoms vary depending on the location of the cancer
Difficulty swallowing1
Chronic sore throat2
Hoarseness1
Lump in throat or neck area1
Cough1
Shortness of breath1
Bleeding in the mouth2
Bleeding in the throat2
Halitosis1
Hearing loss/tinnitus/fluid collection in the ear1
Red or white lesions2
Weight loss1
1. Head and Neck Cancers. The National Cancer Institute neck (Accessed May  2016).
2. Cancer.Net. Head and neck cancers: symptoms and signs. Available at: cancer/symptoms-and-signs (Accessed May 2016).
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Cancer Research UK. and (Accessed 13 March 2017); 2. Luryi AL, et al. JAMA Otolaryngol Head Neck Surg 2014;140(7):639–46.

20. Diagnostic tests for HNSCC
Physical examination:¹
Feeling for lumps on the neck, lips, gums and cheeks, and physical inspection of the nose, mouth, throat and tongue
Biopsy:¹
Fine-needle aspiration is the preferred tissue sampling method for initial evaluation of neck masses or thyroid nodules
HPV testing:²
HPV has been linked to increased risk of some HNSCC; its presence has significant prognostic value
Molecular/biomarker testing:³
Biomarkers for HNSCC include EGFR
Endoscopy:¹
Including laryngoscopy, pharyngoscopy and nasopharyngoscopy
Imaging:1,4
Chest X-ray; head and neck CT scan or MRI (MRI preferable for all subsites except for laryngeal and hypopharyngeal cancers); thoracic CT scan to evaluate possible metastatic disease
Gregoire et al Annals of Oncology 21 (Supplement 5): v184–v186,
Marur et al Mayo Clin Proc. n March 2016;91(3):
Wemmert et al ONCOLOGY LETTERS 11: , 2016
Wennig B Mod Pathol 2002;15(3):229–25
CT, computed tomography; EGFR, epidermal growth factor receptor; HNSCC, head and neck squamous cell carcinoma; HVP, human papillomavirus; MRI, magnetic resonance imaging.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Farah, et al. Chapter 2 in Contemporary Oral Oncology: Biology, Epidemiology, Etiology, and Prevention edited by Moni Abraham Kuriakose 2017; 2. Wemmert, et al Oncol Lett 2016;11:1661–70; 3. Thariat, et al. Clin Cancer Res;2012;18(5):1313–32; 4. Gregoire V, et al Ann Oncol 2010;21(Suppl. 5):v184–v186.

21. Biomarkers Sec62 is a novel potential biomarker for HNSCC¹
HPV-positive tumours have increased expression of p16²
Variable
HPV positive
HPV negative
Race
White > black
Age (y)
40–60
>60
M:F
8:1
3:1
Socioeconomic status
Higher
Low-middle
Smoking/alcohol dependence
Never or minimal
Significant
Marijuana use
Strong association
Unknown
Early sexual experience
Multiple sexual partners
Tumour (T) stage
Early T stage
More advanced T stage
Nodal (N) stage
Advanced N stage
Early N stage
Distant metastasis
DCR (%)
70–90
Second primary rate (%) 11
4.6
Overall response to treatment
2-Year OS (%)
94 (95% CI, 87–100)
58 (95% CI, 49-74)
2-Year PFS (%)
85 (95% CI, 74-99)
53 (95% CI, 36-67)
Wemmert et al ONCOLOGY LETTERS 11: , 2016
Marur et al Mayo Clin Proc. n March 2016;91(3):
Patients with high Sec62 and high nuclear survivin demonstrated a poorer prognosis compared with patients exhibiting low Sec62 and low nuclear survivin expression (p=0.009)
There is a distinct biology and molecular phenotype among HPV-positive OPSCCs when compared with HPV-negative HNSCCs
DCR, distant metastases control rate; F, female; HNSCC, head and neck squamous cell carcinoma; HPV, human papillomavirus; M, male; N, node; OPSCC, oropharyngeal squamous cell carcinoma; T, tumour.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Wemmert S, et al. Oncology letters 2012;11:1661–70; 2. Marur S, et al. Mayo Clin Proc 2016;91(3):386–96.

22. Other genetic markers Chromosomal abnormalities
Over 20 recurrent chromosomal alterations have been identified in invasive HNSCC¹
Loss of heterozygosity near 9p21 is significantly more frequent in recurrent tumours than in non-recurrent tumours2
Amplification of region 11q13 encoding the EGFR gene leads to high expression level of EGFR³
Mutations in genes responsible for squamous differentiation (Notch1, Irf6, Tp63)⁴
Inactivation of TP53 in most cases⁴
Inactivating mutations in NOTCH1⁴
CDKN2A (p16) disruption is reported as a frequent event in HNSCC⁵
Wemmert et al ONCOLOGY LETTERS 11: , 2016
Matsura et al Anticancer Res. 1998 Jan-Feb;18(1A):453-8
Rodrigo et al Scientific Reports 5, Article number: 15698 (2015)
4. Stransy et al Science Aug 26; 333(6046): 1157–1160.
5. International Journal of Cancer Volume 135, Issue 4, Version of Record online: 30 JAN 2014
CDKN2A, cyclin-dependent kinase Inhibitor 2A; EGFR, epidermal growth factor receptor; HNSCC, head and neck squamous cell carcinoma.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. Wemmert S et al Oncol Lett 2016;11:1661–70; 2. Matsuura K et al Anticancer Res 1998;18(1A):453–8; 3. Rodrigo JP et al. Scientific Reports 2015; Article number: 15698; 4. Stransky N et al. Science. 2011;26;333(6046):1157–60; 5. Lim AM et al Int. J. Cancer 2014;135:887–95.

23. Treatment options in HNSCC
HNSCC, head and neck squamous cell carcinoma.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).

24. Primary systemic treatment of HNSCC: NCCN guidelines1
Lip, oral cavity, oropharynx, glottic larynx, supraglottic larynx, ethmoid sinus, maxillary sinus, occult primary: primary systemic therapy and concurrent RT
Nasopharynx: chemoradiation followed by adjuvant chemotherapy
Treatment
Category
High dose cisplatin (preferred) 1
Cetuximab
1,2B*
Carboplatin/infusional 5-FU
5-FU/hydroxurea 2A
Cisplatin/paclitaxel
Cisplatin/infusional 5-FU
Carboplatin/paclitaxel 2B
Weekly cisplatin 40mg/m²
Post-operative chemoradiation
Cisplatin
1**
Treatment
Category
Cisplatin + RT followed by cisplatin/5-FU or carboplatin/5-FU
2B (Carboplatin/5-FU)
Cisplatin + RT without adjuvant chemotherapy 2B
*Category 1 for oropharynx, hypopharynx or larnyx; 2B for lip, oral cavity, ethmoid sinus, maxillary sinus, occult primary. **Category 1 for high risk non-oropharyngeal cancers. 5-FU, fluorouracil; HNSCC, head and neck squamous cell carcinoma; NCCN, National Comprehensive Cancer Network; RT, radiotherapy.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. NCCN Clinical Practice Guidelines in Oncology. Head and Neck Cancers, Version 1. Published: February 6th 2017.

25. Treatment of recurrent, unresectable or metastatic HNSCC: NCCN guidelines1
Combination therapy*
Single agents*
Treatment
Category
Cisplatin or carboplatin/5-FU/cetuximab (non-nasopharyngeal) 1
Cisplatin or carboplatin/docetaxel or paclitaxel 2A
Cisplatin cetuximab (non-nasopharyngeal)
Cisplatin/5-FU
Cisplatin or carboplatin/docetaxel/cetuximab (non-nasopharyngeal)
Cisplatin or carboplatin/paclitaxel/cetuximab (non-nasopharyngeal)
Carboplatin/cetuximab (nasopharyngeal)
Cisplatin/gemcitabine (nasopharyngeal)
Gemcitabine/vinorelbine (nasopharyngeal)
Treatment
Category
Cisplatin 2A
Carboplatin
Paclitaxel
Docetaxel
5-FU
Methotrexate
Cetuximab (non-nasopharyngeal)
Gemcitabine (nasopharyngeal)
Capecitabine
Afatinib** 2B
Pembrolizumab**
Nivolumab** 1
*Surgery or radiotherapy not an option. **Non-nasopharyngeal, if disease progression on or after platinum-containing chemotherapy. HNSCC, head and neck squamous cell carcinoma; NCCN, National Comprehensive Cancer Network.
This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK).
1. NCCN Clinical Practice Guidelines in Oncology. Head and Neck Cancers, Version 1. Published: February 6th 2017.

26. Abbreviated EU SmPC
EGFR M+ NSCLC and sqNSCLC GIOTRIF®: Irreversible ErbB family blocker. Active substance: Afatinib. Indications: GIOTRIF is indicated as monotherapy for (1) patients with locally advanced or metastatic NSCLC with activating EGFR mutations not previously treated with EGFR TKIs, (2) patients with NSCLC of squamous histology progressing on or after platinum-based chemotherapy. Posology: The recommended dose is 40 mg once daily, orally. Not recommended in patients with an eGFR <15ml/min and severe hepatic impairment. Contraindications: Hypersensitivity to afatinib or any of the excipients. Interactions: Potent P-gp inhibitors may lead to increased afatinib exposure, concomitant treatment with potent P-gp inducers may lead to a reduction in afatinib exposure. Afatinib is not an inhibitor or inducer of CYP enzymes. Undesirable effects: Paronychia, cystitis, decreased appetite, dehydration, hypokalaemia, dysgeusia, conjunctivitis, dry eye, epistaxis, rhinorrhoea, diarrhoea, stomatitis, nausea, vomiting, cheilitis, dyspepsia, alanine aminotransferase increased, aspartate aminotransferase increased, rash, acneiform dermatitis, pruritus, dry skin, palmar-plantar erythrodysaesthesia syndrome, nail disorders, Stevens-Johnson syndrome, toxic epidermal necrolysis, muscle spasms, renal impairment/renal failure, pyrexia, weight decreased, interstitial lung disease, keratitis, pancreatitis. Presentations: 20 mg, 30 mg, 40 mg, and 50 mg film-coated tablets. For detailed information, please refer to the published Prescribing Information. Supply classification: POM. This medicine is subject to additional monitoring. Boehringer Ingelheim International GmbH, Binger Strasse 173, Ingelheim am Rhein, Germany EGFR M+, epidermal growth factor receptor mutation positive; NSCLC, non-small cell lung cancer; TKI, tyrosine kinase inhibitor. Date of text revision: July 2017