Humaan Papillomavirus en hoofd/halskanker - UZA · Humaan Papillomavirus en hoofd/halskanker...

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Pol Specenier [email protected] Humaan Papillomavirus en hoofd/halskanker

Transcript of Humaan Papillomavirus en hoofd/halskanker - UZA · Humaan Papillomavirus en hoofd/halskanker...

Pol Specenier

[email protected]

Humaan Papillomavirus en hoofd/halskanker

Humaan Papillomavirus en hoofd/halskanker

• Hoofd/halskanker: incidentie en oorzaken

• Oropharynx carcinoom

– Incidentie

– HPV

– HPV en prognose

– Behandeling

– Preventie

Humaan Papillomavirus en hoofd/halskanker

• Hoofd/halskanker: incidentie en oorzaken

• Oropharynx carcinoom

– Incidentie

– HPV

– HPV en prognose

– Behandeling

– Preventie

Incidence Belgium

Mortality Belgium

Incidence Head and Neck Cancer Belgium 2011

0 100 200 300 400 500 600

Parotid gland

Salivary glands, NOS

Nasal cavity and middle ear

Accessory sinuses

Nasopharynx

Larynx

Pyriform sinus

Hypopharynx

Tonsil

Oropharynx

Lip

Base of tongue

Tongue

Gum

Floor of mouth

Palate

Mouth, NOS

Lip, oral cavity and pharynx, NOS

Males

Females

Incidence Head and Neck Cancer Belgium 2011

0 100 200 300 400 500 600

Parotid gland

Salivary glands, NOS

Nasal cavity and middle ear

Accessory sinuses

Nasopharynx

Larynx

Pyriform sinus

Hypopharynx

Tonsil

Oropharynx

Lip

Base of tongue

Tongue

Gum

Floor of mouth

Palate

Mouth, NOS

Lip, oral cavity and pharynx, NOS

Males

Females

Squamous Cell

Carcinoma (SCCHN)

Incidence Head and Neck Cancer Belgium 2011

0 100 200 300 400 500 600

Parotid gland

Salivary glands, NOS

Nasal cavity and middle ear

Accessory sinuses

Nasopharynx

Larynx

Pyriform sinus

Hypopharynx

Tonsil

Oropharynx

Lip

Base of tongue

Tongue

Gum

Floor of mouth

Palate

Mouth, NOS

Lip, oral cavity and pharynx, NOS

Males

Females

Squamous Cell

Carcinoma (SCCHN)

Fraction of SCCHN due to alcohol, tobacco, or both

Tobacco + alcohol

Tobacco alone

Alcohol alone

Fraction of SCCHN due to alcohol, tobacco, or both

Tobacco + alcohol

Tobacco alone

Alcohol alone

Tobacco Smoking and Head and Neck Cancer: INHANCE

Wyss A et al. Am J Epidemiol. 2013; 178(5):679-90

Involuntary Tobacco Smoking and UADT

Lee YCA et al. Cancer Epidemiol Biomarkers Prev 2009;18: 3353-3361.

Marron M et al. Int J Epidemiol. 2010; 39(1):182-96

Humaan Papillomavirus en hoofd/halskanker

• Hoofd/halskanker: incidentie en oorzaken

• Oropharynx carcinoom

– Incidentie

– HPV

– HPV en prognose

– Behandeling

– Preventie

Humaan Papillomavirus en hoofd/halskanker

• Hoofd/halskanker: incidentie en oorzaken

• Oropharynx carcinoom

– Incidentie

– HPV

– HPV en prognose

– Behandeling

– Preventie

Incidence oropharyngeal cancer

Chaturvedi AK. Head and Neck Pathol 2012; 6:S16–S24

Oropharyngeal cancer incidence: US

Chaturvedi AK et al. J Clin Oncol 2011; 29:4294-4301

Larynx

Oral cavity

Oropharynx

Oropharyngeal cancer incidence: Sweden

Ramqvist T, Dalianis T. Emerg Infect Dis. 2010; 16(11):1671-7

Incidence HPV+ and HPV- tonsillar SCC: Sweden

Ramqvist T, Dalianis T. Emerg Infect Dis. 2010; 16(11):1671-7

Proportion HPV+ tumors

Marur S et al. Lancet Oncol 2010; 11: 781–89

HPV status and prognosis

Rietbergen MM et al. Int J Cancer 2013; 132: 1565-71

Prevalence HPV markers according to tumor site

Combes JD, Franceschi S. Oral Oncol 2013;

http://dx.doi.org/10.1016/j.oraloncology.2013.11.004

Humaan Papillomavirus en hoofd/halskanker

• Hoofd/halskanker: incidentie en oorzaken

• Oropharynx carcinoom

– Incidentie

– HPV

– HPV en prognose

– Behandeling

– Preventie

Kleine niet-omkapselde DNA

virussen, dubbelstrengig genoom dat

codeert voor

6 vroege (E1, E2, E4, E5, E6, E7)

2 late proteinen (L1, L2)

HPV

Best SR et al. Otolaryngol Clin North Am 2012; 45(4): 807–822

E6 oncoproteine leidt tot ubiquinatie

en degradatie tumor suppressor p53

deregulatie van de G1/S and

G2/M cell cycle checkpoints

HPV

Ghittoni R et al. Virus Genes 2010; 40:1–13; Narisawa-Saito M et al. Cancer Sci

2007; 98: 1505–1511; Best SR et al. Otolaryngol Clin North Am 2012;

45(4): 807–822

E7 oncoproteine: degradatie

retinoblastoma tumor suppressor

gene product (pRB)

(E5 zorgt voor upregulatie EGFR)

HPV

Ghittoni R et al. Virus Genes 2010; 40:1–13; Narisawa-Saito M et al. Cancer Sci

2007; 98: 1505–1511; Best SR et al. Otolaryngol Clin North Am 2012;

45(4): 807–822

HPV-related cancer cases US 2009

Jemal A et al. J Natl Cancer Inst 2013;105:175–201

Incidence cervical and oropharyngeal cancer

Chaturvedi AK et al. J Clin Oncol 2011; 29:4294-4301

Bosch FX et al. Vaccine 2013; 31S: H1–H31

Oral HPV infection prevalence

Kreimer AR et al. Cancer Epidemiol Biomarkers Prev 2011;20:172-182

Oral HPV infection prevalence

Chung CH et al. Oral Oncol 2013; http://dx.doi.org/10.1016/

j.oraloncology.2013.09.003

Oral HPV infection prevalence

Gillison ML et al. JAMA 2012; 307: 693-703.

Oral HPV infection prevalence

Gillison ML et al. JAMA 2012; 307: 693-703.

HPV + and – tumors: characteristics

Marur S et al. Lancet Oncol 2010; 11: 781–89

Lewis JS et al. Am J Surg Pathol. 2010; 34(8): doi:10.1097/PAS.0b013e3181e84652

Zandberg DP et al. CA Cancer J Clin 2013;63:57-81.

Humaan Papillomavirus en hoofd/halskanker

• Hoofd/halskanker: incidentie en oorzaken

• Oropharynx carcinoom

– Incidentie

– HPV

– HPV en prognose

– Behandeling

– Preventie

HPV and prognosis

Chaturvedi AK. Head and Neck Pathol 2012; 6:S16–S24

HPV and survival: RTOG 0129

Ang KK et al. N Engl J Med 2010;363:24-35

HPV and survival: RTOG 0129

HPV-16 DNA ISH HPV-16 negative 12 additional oncogenic HPV types (18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68)

p16 ICH; positive = strong and diffuse nuclear and cytoplasmic staining in 70% or more of the tumor cells

Ang KK et al. N Engl J Med 2010;363:24-35

Lassen P et al. Radiother Oncol 2013; 108: 489–494

Correlatie p16 en HPV

Ang KK et al. N Engl J Med 2010;363:24-35

Kappa = 0.8; 95 % CI: 0.73-0.87

HPV and survival: RTOG 0129

Ang KK et al. N Engl J Med 2010;363:24-35

HPV-16: 96.1 %

HPV and survival: RTOG 0129

Ang KK et al. N Engl J Med 2010;363:24-35

HPV and survival: RTOG 0129

Ang KK et al. N Engl J Med 2010;363:24-35

HPV and prognosis

Posner MR et al. Ann Oncol 2011; 22: 1071–1077.

TAX 324 TROG 02.02

Rischin R et al. J Clin Oncol 2010; 28:4142-4148

HPV and prognosis

Fischer CA et al. Ann Oncol 2010; 21: 1961-1966

HPV detectie technieken

Mirghani H et al. Oral Oncol 2014

http://dx.doi.org/10.1016/j.oraloncology.2013.10.008

Mirghani H et al. Oral Oncol 2014

http://dx.doi.org/10.1016/j.oraloncology.2013.10.008

Mirghani H et al. Oral Oncol 2014

http://dx.doi.org/10.1016/j.oraloncology.2013.10.008

Humaan Papillomavirus en hoofd/halskanker

• Hoofd/halskanker: incidentie en oorzaken

• Oropharynx carcinoom

– Incidentie

– HPV

– HPV en prognose

– Behandeling

– Preventie

Patient

Surgeon Medical

Oncologist

Dietician

Radiologist

Social worker

Psychologist

Nurse

Speech Therapist

Dentist

GP

Radio-therapist

Pathologist

Oropharyngeal cancer: treatment

www.nccn.org

Oropharyngeal cancer: treatment

www.nccn.org

Oropharyngeal cancer: treatment

www.nccn.org

Pignon JP et al. Radiother Oncol 2009; 92: 4–14

MACH-NC: concomitant CRT

Oropharyngeal cancer: treatment

www.nccn.org

Oropharyngeal cancer: treatment

www.nccn.org

Oropharyngeal cancer: treatment

www.nccn.org

Bernier J et al. Head Neck 2005; 27: 843-850

Oropharyngeal cancer: treatment

www.nccn.org

De-escalation?

Kofler B et al. Eur Arch Otorhinolaryngol DOI 10.1007/s00405-013-2603-0

Kofler B et al. Eur Arch Otorhinolaryngol DOI 10.1007/s00405-013-2603-0

Humaan Papillomavirus en hoofd/halskanker

• Hoofd/halskanker: incidentie en oorzaken

• Oropharynx carcinoom

– Incidentie

– HPV

– HPV en prognose

– Behandeling

– Preventie

Kreimer AR et al. Cancer Epidemiol Biomarkers Prev 2005;14: 467-475

HPV types in oropharyngeal cancer

Kreimer AR et al. Cancer Epidemiol Biomarkers Prev 2005;14: 467-475

Kreimer AR et al. Cancer Epidemiol Biomarkers Prev 2005;14: 467-475

Herrero Ret al. PLoS One. 2013 Jul 17;8(7):e68329. doi: 10.1371/

journal.pone.0068329

Prevalence oral infections HPV16/18

Herrero Ret al. PLoS One. 2013 Jul 17;8(7):e68329. doi: 10.1371/

journal.pone.0068329

Oral infections HPV other than 16/18

Herrero Ret al. PLoS One. 2013 Jul 17;8(7):e68329. doi: 10.1371/

journal.pone.0068329

Dank U

HPV status and EGFR expression

Mirghani H et al. Eur J Cancer 2014; http://dx.doi.org/10.1016/j.ejca.2013.12.018

HPV status and EGFR expression

Lassen P et al. Radiother Oncol 2013; 108: 489–494

Robinson M et al. Head and Neck Pathol 2012; 6: S83–S90

HPV attributable cancers 2004-2008: US

MMWR. 2012; 61 (15)

Tobacco Smoking and Head and Neck Cancer: INHANCE

Wyss A et al. Am J Epidemiol. 2013; 178(5):679-90

Alcoholic Beverage and Head and Neck Cancer: INHANCE

Purdue MP et al. Am J Epidemiol 2009; 169(2):132-42

Alcohol-tobacco interaction

Kreimer AR et al. Cancer Epidemiol Biomarkers Prev 2005;14: 467-475