SM_272b: Head and Neck Cancer Flashcards
___ are more likely to get head and neck cancer
Males are more likely to get head and neck cancer
Describe risk factors for head and neck cancer
Risk factors for head and neck cancer
- Age: > 50
- Tobacco
- Alcohol
- Viral: EBV (nasopharyngeal), HPV (oropharynx, oral)
- Plummer-Vinson syndrome (iron deficiency)
- Hereditary (rare): family history increases risk, rare genetic syndromes such as Fanconi’s anemia
Describe groups of head and neck cancer
Head and neck cancer
- HPV-related cancers: caused by high-risk HPV (16) and driven by viral oncogenes, restricted to oropharynx (base of tongue and tonsil), distinct molecular markers, good prognosis, young and in good general health
- Environment-related cancers: caused by environmental mutagens (smoking, alcohol, woodwork), throughout oral mucosa / field cancerization, distinct molecular markers, poor prognosis and comorbidity, second cancers
HPV is a ___ virus
HPV is a dsDNA virus
Describe HPV
HPV
- dsDNA
- Infections epithelial cells in skin and oral / genital / anal mucosa in key areas
- Aysmptomatic
- > 100 different genotypes
- Benign: 6 and 11
- High risk: 16 and 18
- Exposure to marijuana
____ is most common in HPV+ oropharyngeal cancer
HPV16 is most common in HPV+ oropharyngeal cancer
- HPV 16 and 18 are high risk
Describe epithelial cell transfection by HPV
Epithelial cell transfection by HPV
- Immune escape -> persistent HPV infection
- Viral oncoproteins E6 and E7 mediate malignant transformation in infected cell
- HPV depends on host cell replication proteins for viral DNA synthesis
HPV ___ and ___ associate with and reprogram cellular enzymes
HPV E6 and E7 oncoproteins associate with and reprogram cellular enzymes
- Target associated cellular tumor suppressors for degradation
HPV16 E6 ___
HPV16 E6 retargets the cellular ubiquitin ligase E6AP to the p53 tumor suppressor protein
HPV16 E7 ___
HPV16 E7 retargets the cellular cullin 2 ubiquitin ligase complex to the retinoblastoma tumor suppressor protein pRB
Describe oncogenic effect of HPV E6 and E7 proteins on host cells
Oncogenic effect of HPV E6 and E7 proteins on host cells
- p53, Rb degradation / loss: cell is lead to path of uncontrolled proliferation -> malignant transformation
- Rb degradation -> activation of E2F transcription factor -> drives cell cycle from G1 to S phase -> expression of S phase genes -> hyperproliferation
Describe function of p16
p16
- p16 inhibits CDK
- de-pRb
- transcriptional repression
- Cell cycle control
inhibited by oncogenic changes
Describe the role of p16 in the Rb pathway
Role of p16 in the Rb pathway
- Rb proteins suppress transactivation factor of E2F -> inhibit transcription
- Phosphorylation of Rb proteins by CDK4/6 -> disrupts Rb + E2F interaction -> unbound / activated E2F -> S phase gene transcription -> G1 to S phase -> cell proliferation
- Degradation of Rb by E7 -> overexpression of p16 (feedback loop) -> surrogate marker for HPV+ oropharyngeal cancer
Describe presentation of oropharyngeal cancer
Oropharyngeal cancer presentation
- Lesions in mouth: persistent mass or ulcer, usually in oral cavity
- Persistent hoarseness
- Persistent sore throat
- Difficulties in moving tongue or jaws: chewing, swallowing, or speaking
- Palpable mass in neck
- Ear pain: otalgia
Describe diagnostic evaluation of head and neck cancer
Diagnostic evaluation of head and neck cancer
- ENT
- Indirect largyngoscopy: using mirros to visualize the larynx
- Transnasal flexible fiberoptic laryngoscopy: direct visualization of oral / nasal cavity, nasopharynx, oropharynx, larynx
- FNA biopsy
- Panendoscopy (under anesthesia: laryngoscopy / esophagoscopy / bronchoscopy, biopsies
Cancer of head and neck appears as ___ on pathology
Cancer of head and neck appears as squamous cell carcinoma ± keratinization on pathology
- Squamous cell carcinoma of larynx: poorly differentiated, hyperchromatic nuclei, polymorphism, high nucleus to cytoplasm ratio
- Squamous cell carcinoma with basaloid features: more aggressive, can be seen in HPV tumors, basophilic oval tumors, high nucleus to cytoplasm ratio
- Keratinization: keratin pearls
HPV tumors of head and neck stain for ___
HPV tumors of head and neck stain for p16
Describe diagnostic evaluation of head and neck cancer
Diagnostic evaluation of head and neck cancer
- CT neck with contrast: assess extent of primary tumor, assess lymphadenopathy
- PET/CT: staging
- MRI: only if needed to assess for resectability
Staging of head and neck cancer involves ___
Staging of head and neck cancer involves TNM staging
- T staging is individualized to each site of origin
Describe TNM staging of head and neck cancer
TNM staging of head and neck cancer
- T
- T1, T2: small tumors, localized
- T3: large tumors, invading adjacent structures
- T4: locally advanced tumor, invading surrounding structures
- N
- N1: ispilateral single lymph node ≤ 3 cm
- N2a: ipsilateral single lymph node 3-6 cm
- N2b: multiple ipsilateral lymph nodes all < 6 cm
- N2c: bilateral lymph nodes, all < 6 cm
- N3: lymph node > 6 cm
Describe treatment of head and neck cancer
Head and neck cancer treatment
- Early stage (I, II: localized T1-2N0M0): radiation or surgery
- Locally advanced (III, IVA, IVBL T1-4N1-3M0): multi-modality therapy
- Metastatic recurrent: palliative chemo, immune therapy, targeted therapy
Describe challenges of surgery for head and neck cancer
Challenges of surgery for head and neck cancer
- Disfigurement and dysfunction
- Voice loss, inability to eat / speak / swallow
- Tracheostomy
- Psychological and physical stresses: reduced quality of life
Described advanced stage laryngeal carcinoma
Advanced stage laryngeal carcinoma
- Most patients with induction did not require laryngectomy
- Trend towards benefit in reduction of metastatic disease in chemo arms
- Adding chemotherapy improved survival
Adjunctive chemotherapy ___ survival in head and neck cancer
Adjunctive chemotherapy improves survival in head and neck cancer
Chemoradiation ___ outcomes in head and neck cancer
Chemoradiation improves outcomes in head and neck cancer
Describe role of HPV in head and neck cancer
HPV
- Strong association with oropharynx
- Non-smokers, non-drinkers
- Younger age, male predominance
- HPV 16
- Better prognosis compared with non-HPV associated head and neck cancer
- Detection: accuracy better with ISH or PCR, practicality better with p16 IHC
Describe field cancerization
Field cancerization
- Areas surrounding cancer are genetically abnormal clones
- Multiple areas of precancer and cancer exist
- Occurs in response to carcinogen exposure
- Explains high rate of recurrence following resection of cancer
