HPV Associated Oropharyngeal Carcinomas Flashcards
1
Q
What percentage of oropharyngeal cancers are caused by viral infection in the UK? What is the remainder usually caused by?
A
80%
Remainder caused by smoking and alcohol
2
Q
What types of HPV cause carcinomas and what is the overall risk?
A
- Most common carcinogenic types are types 16 and 18 - most common sexually transmitted infection
- Most people’s immune systems clear the infection in under a year and the overall risk of developing carcinoma is very low
- Persistent or repeated infection carries the highest risk
3
Q
How can genital papillomavirus be transmitted to the mouth
A
- Oral sex, through transmission across the placenta during birth or shortly after
4
Q
Where do carcinomas form more frequently?
A
More frequently in the oropharynx than in the cervix
5
Q
What is the pathogenesis of HPV associated carcinomas
A
- HPV oropharyngeal carcinomas arise specifically in the tonsil and minor tonsils of Waldeyer’s ring around the base of the tongue, soft palate and pharynx
- Tonsil crypt are lined by non-keratinised and permeable epithelium
- HPV infects the crypt lining epithelial cells and the viral DNA either integrates into their DNA or remains in cytoplasm
- Viral proteins (E6, E7) bind to and inactivate the tumour suppressor proteins p53 and retinoblastoma protein => inhibits apoptosis, increases cell proliferation, generates genomic instability => after prolonged latent period of 20-30 years, carcinoma may result
6
Q
What is the clinical presentation of HPV carcinomas
A
- Arise in young patients
- Half of pts seen with cervical lymph node metastasis producing masses in the neck (unusual presentation: soft, usually single and often cystic and only become fixed at late stage)
- 1/3 pts seen with sore throat
- Clinical examination unlikely to detect primary carcinoma
1. metastases often the first sign of disease
2. only 15% will have visible lesion as carcinoma arise inside tonsil crypts without producing surface mass
3. typically metastasises very early and the primary tumour may only be few mm across when metastasis becomes evident
7
Q
What investigations can be done to show HPV oropharyngeal cancer
A
- Fine needle aspiration of neck mass => shows squamous cell carcinoma => triggers search for primary site
- If appearance suggest an oropharyngeal primary, or if papillomavirus is detected in the sample => search for primary site using imaging, bilateral tonsillectomy, adenoidectomy or biopsies of posterior tongue
8
Q
What treatment can be done for HPV associated oropharyngeal cancer
A
- Chemo-radiotherapy is usual tx, but surgery if carcinoma is accessible is also highly effective
- HPV associated carcinomas have better prognosis than carcinomas induced by tobacco and alcohol (95% survive 3 years where as only 60% survive 3y with conventional carcinomas)
- If pts smoke and drink they have additional carcinogenic effect that creates more aggressive carcinoma and response to tx is slightly worse
- This type of carcinomas should be prevented by vaccination. Girls aged 12-13 before first sexual contact should get vaccine which protects against type 6, 11, 16, 18
9
Q
What Is the significance of HPV in oral carcinomas
A
- HPV found in ~5% of intraoral carcinomas
- However, infection in the population is common making the significance unclear
- There is no evidence yet that papillomavirus plays a role in inducing oral carcinomas
10
Q
What is the difference between tobacco + alcohol induced carcinomas and HPV associated carcinomas
A
- T&A often have precursor dysplastic lesions whereas HPV does not
- T&A present as visible ulcer or mass whereas HPV primary carcinoma is invisible
- T&A usually symptomatic whereas HPV is usually asyptomatic
- T&A has late metastases whereas HPV has early metastases
- T&A causes hard fixed multiple lymph node metastases whereas HPV causes soft cystic solitary lymph node metastases
- T&A primary is large whereas HPV is small
- T&A has poor response to treatment whereas HPV has good response to tx
