Human Papilloma viruses and Cervical cancer Flashcards
What is cervical cancer?
Cancer that is found anywhere within the cervix
How many women are diagnosed with cervical cancer?
- 2800/year in UK
- 500,000/year worldwide
What is the mortality rate of cervical cancer?
1000 per year
What is the demographic for cervical cancer?
Sexually active women aged 25-45
What are the 2 types of cervical cancer?
Squamous cell and Adenocarcinoma
What is squamous cell cervical cancer?
- cancer found in squamous cells which are surface cells of the cervix
- most common type (80%)
What is adenocarcinoma cervical cancer?
- cancer found in the mucus-producing glands within the endocervix
- less common
How is cervical cancer detected?
- Screening is used to detect precancerous cellular anomalies (dysplasia)
- reduced incidence by effective treatment/surgery
What is the survival rate of cervical cancer?
- depends on its stage and the patient’s age
- 5+ year survival = 95% stage l, 15% stage lV
What are symptoms of early cervical cancer?
- usually little/no symptoms
- Unusual bleeding
- unusual discharge
- pain
What are symptoms of advance cervical cancer?
- haematuria
- constipation
- bone pain
What is cervical intraepithelial neoplasia (CIN)?
- a precancerous viral condition caused by HPV (16/18) that produces potentially malignant lesions
- shows changes in the cervical cells which can be detected with screening
- can be treated successfully
- almost all women with cervical cancer have been infected with the virus
- Spread through sexual intercourse
What are causes/risk factors of cervical cancer?
- infection with HPV (16/18)
- infection with other sexually transmitted diseases (chlamydia/HIV) that weaken the immune system
- smoking
- contraceptive pill
- no regular screening
- IDEA THAT THERE IS AN INFECTIOUS AGENT INVOLVED BUT NOT IDENTIFIED
How is cervical cancer diagnosed?
- abnormal cervical smear test that is offered to women aged 25-64 to detect CIN
What vaccinations are there for cervical cancer?
- Gardasil - HPV 16/18/6/11
- Cervarix - HPV 16/18
- must be given before exposure: <12 yrs for girls, unknown for boys
- effective for at least 6 years
What further tests are done if the smear test is abnormal?
- Colposcopy = microscope used to look directly at the cervix to detect any dysplastic cells
- Biopsy = for microscopic examination for cancer
- MRI, PET scan, X-ray
What happens to the arrangement of the cervical cells as cancer progresses?
- cells start in a normal arrangement but as CIN progresses the tissue becomes more disorganised and eventually there is a large increase in cells resulting in invasive cancer
- the changes start in the basal cell layers and then go through to encompass the entire epithelium
What are treatments for cervical cancer?
- pathology, stage, curative/palliative, patient factors all need to be taken into account
1. Local surgical excision
2. Hysterectomy
3. Radiotherapy
4. Chemotherapy
What are the different stages of cervical cancer?
- Stage l - carcinoma confined to cervix
- Stage lA - invasive cancer identified only microscopically
- Stage lB - clinical lesion confined to cervix
- Stage ll - cancer extends beyond cervix but not to pelvic wall
- Stage lll - cancer has extended on to pelvic sidewall
How does HPV cause cancer?
- several HPV types can produce malignant lesions which have potential to be malignant and cause common carcinoma of the uterine cervix
What are human papilloma viruses (HPVs)?
- large group (approx 100) of small DNA tumour viruses
- infect cutaneous and mucosal epithelial tissue
- Usually give benign hyperplasia/warts that regress spontaneously
How do DNA tumour viruses cause cancer?
- have cancer causing mechanisms
- encode oncoproteins using host cells which are distinct from their proteins
- viral oncoproteins inactivate tumour suppressor proteins resulting in uncontrollable growth
What are the high and low risk cancer types of HPV?
- High risk = HPV16/18, found in 95% cases
- Low risk = HPV6/11, usually benign
What is the latency period of HPV?
- first developed in sexually active 15-25yrs old then seen in 40-50yrs old when a carcinoma becomes visible
What are characteristics of the HPV genome?
- difficult to culture
- replication depends on host cell proliferation
What are characteristics of HPV malignant cells?
- partial HPV sequences
- intergrated into host DNA
- E2 open reading frame usually disrupted
- deregulation of E6/E7 region
Which tumour suppressor proteins does HPV inactivate?
HPV E7/E6 inactivate Rb and p53 respectively
How does HPV interrupt the cell cycle?
- E7 proteins from HPV bind to pRb
- sequestration removes Rb from cell cycle regulation which facilitates cell from growth suppression
- oncoproteins produced bind to HYPO-phosphorylated pRb to act as a gatekeeper
- this results in the cell cycle transit becoming blocked
What is p53?
- nuclear protein found in normal cells at low levels
- known as the guardian of the genome as it protects cell through cell cycle arrest and apoptosis
- when there is cellular stress, levels of p53 rapidly increase
What happens when p53 is inactivated?
- cancer cells must inactivate p53 pathway to be able to divide rapidly and survive
- SV40 virus contains protein large T which binds to p53, resulting in its inactivation
- this leads to the inhibition of apoptosis and allows the proliferation of cancer cells, resulting in tumourigenesis
