Papilloma virus and cervical cancer Flashcards
What are the two types of cervical cancer?
- squamous cell cervical cancer - most common = 85%
- adenocarcinoma cervical cancer - less common
What is the survival rate of cervical cancer?
- depends on stage and age. advanced = 1 in 3 will live at least 5 years
What is the incidence of cervical cancer?
- about 2800 women per year in UK. 500,000 cases pa worldwide. mortality = 1000 women per year
Most cases in sexually active women between 25-45
What are the symptoms of cervical cancer?
- early staged = no symptoms
- unusual bleeding
- unusual discharge
- pain
- advanced cervical cancer = haematuria, constipation, bone pain
What is CIN?
- Cervical intraepithelial neoplasia
- takes many years to develop
- precancerous condition = CIN, in which cells of cervix show changes. screening can detect these changes
- nearly all cases of cervical cancer occur in women who have been infected with the virus. more than 100 different types of HPV-only a subset linked to cervical cancer
- HPV 16 and 18 associated with >70% of cancers
- virus infection causes CIN
- spread through sexual intercourse
What are the causes and risk factors of cervical cancer?
- infection with HPV
- other sexually transmitted diseases - chlamydia or HIV
- increased exposure to HPV - sexual activity
- smoking
- contraceptive pill
- no screening
How is cervical cancer diagnosed?
- abnormal cervical smear test - papanicalou test = offered to women 25-64 years of age. Detects preinvasive step
What happens if the cervical screening is abnormal?
- colposcopy - microscope used to look at cervix directly
- biopsy - for microscopic examination for cancer. MRI, PET scan, chest X-ray
What are the stages of cervical cancer?
stage I - carcinoma confined to cervix
stage IA - invasive cancer identified only microscopically
stage IB - clinical lesion confined to cervix
stage II - extends beyond cervix but not to pelvic wall
stage III - extended on to pelvic sidewall
treatment - take account of pathology, staging, curative or palliative patient factors eg. co-morbidities, treatment…
local surgical excision, hysterectomy, radiotherapy, chemotherapy
5 year survival: 95% (stage I) 15% (stage IV- disseminated disease)
Vaccinations for cervical cancer
- 2 HPV vaccine reduce risk of cancerous or precancerous changes of the cervix
- gardasil - HPV 16, 18 and 6
- cervarix - HPV 16 and 18
- must be given before viral exposure: girls at 12 years
- effective for at least 6 years
Describe HPV
- large group (100) small DNA tumour virus
- infect cutaneous and mucosal epithelial tissue
- most HPV give benign hyperplasia - warts that regress spontaneously
- BUT several HPV types cause lesions with malignant potential - genital HPV infection cause of carcinoma of the uterine cervix - a v common cancer
- high risk HPV types - 16 and 18
- low risk = 6 and 11
What happens when the virus (HPV16) infects the cell?
- DNA enters cell and replicates as episome
- with time = disruption of episome and insertion into host chromosomes
- insertion knocks out E2 gene (transcription factor that regulates expression of E6 and E7)
- E6 and E7 get expressed in v high levels
Why is it difficult to understand the HPV genome and replication?
- difficult to culture HPV
- in benign productive lesions, HPV present as multiple episomal copies.
- malignant cells have : only partial HPV sequences, integrated into host DNA, integration sites not consistent, E2 usually disrupted
What has been learnt from DNA tumour viruses?
- cancer causing mechanism distinct from retroviruses
- encode oncoproteins distinct from proteins produced by host cells
- viral oncoproteins inactivate tumour suppressor proteins: provide key insights into negative growth control in cells. eg. HPV E6 and E7 bind and inactivate RB and p53
Where do the viral oncoproteins bind to pRB?
- E1A, large T and E7 proteins bind pRb
- sequestration removes Rb from cell cycle regulation - same outcome as loss of two RB genes through mutation in retinoblastoma. Facilitates cell from growth suppression
- DNA tumour virus oncoproteins preferentially bind HYPO-phosphorylate pRb.
- this form is involved in acting as a gate keeper, blocking cell cycle transit
