Cervical Cancer and melanoma Flashcards
1
Q
Role of Viruses in Cancer
A
- Viruses account for ~20% of human cancer
- Seven viruses are associated with human cancers and are considered oncogenic:
- HBV, HCV, HPV, Epstein Barr Virus, human herpes virus 8, Merkel cell polymavirus, and HTLV-1
2
Q
What viruses are associated with different types of cancer
A
- HBV & HCV - cause ~80% of hepatocellular carcinoma
- HPV - high risk HPV strains are the major cause of cervical cancer and other ano-genital neoplasms as well as head and neck tumours
- Epstein Barr - nasopharyngeal carcinoma, Hodgkin’s lymphoma, and Burkitt’s lymphoma
- HHV 8 - responsible for kaposi’s sarcoma
- MCPyV - Merkel cell carcinoma
- HTLV-1 - adult T-cell lymphoma
3
Q
Mechanims of Viral Oncogenesis
A
- May involve induction of chronic inflammatory, disruption of host genetic and epigenetic integrity and homeostasis, interference with cellular DNA repair mechanisms resulting in genome instability and cell cycle dysregulation. Furthermore, oncogenic DNA viruses can also insert their genomic DNA into cellular chromosomes, resulting in genetic abnormaity.
- Viral oncoproteins have the ability to activate cellular signaling pathways, alter gene expression, and inactivate tumour suppressor proteins and proteins that regulate cell polarity, signal transduction, immune response, and apoptosis.
4
Q
Cervical Cancer
A
- One of the most common gynecological malignances with peak incidence between 40-50 years.
5
Q
Risk Factors Cervical Cancer
A
- Sexual activity - with major cause being infection with HPV. Most HPV infections occur in young women and are transient and do not cause cervical cancer. However, there are certain high grade HPV subtypes (i.e., 16, 18) that have a strong association with high-grade lesion, persistence, and progression to cervical cancer. (HPV plays a role in both squamous cell carcinoma and adenocarcinoma.
- Early onset of sexual activity
- Multiple sexual partners
- History of STIs
- History of vulvar or vaginal squamous intraepithelial neoplasia or cancer
- Co-factors - immunosuppression, smoking
6
Q
Pathogenesis Cervical Caner
A
- Oncogenic HPV infection of metaplastic (reversible transformation from one cell type to another) epithelium at cervical transformation zone.
- Persistence of HPV infection
- Progression of a clone of epithelial cells from persistent viral infection to precancer.
- Development of carcinoma and invasion through basement membrane.
7
Q
Pathology Cervical Cancer
A
- Changes are often maximal at the junction zone where the squamous epithelium of the ectocervix meets the cuboidal epithelium of the endocervix close to, or at, the external OS. Changes can be single focus, multiple foci, or continuous extending up the endocervical canal.
- CIN (cervical intraepithelial neoplasia) 1 (mild) or 2 (moderate), or abnormal growth of cervical cells, are common is sexually active females . CIN 3 (severe) changes are more commonly part of the process that can progress over months or years to invasive carinoma.
- Most patients have changes to the squamous cells (69%), others have adenomatous cell changes (25%), or a mixture of both (adenosquamous tumour)
8
Q
Clinical Features Cervical Cancer
A
- Early cervical cancer is frequently asymptomatic
- Symptoms may include: abnormal vaginal bleeding after sex; discharge; pelivc pain; and dyspareunia (painful sex).
- Increasing tumour size and pelvic infiltration can lead to pressure on the bladder (frequency), rectum (altered bowel habits), or ureters (uremia).
9
Q
Examination Findings Cervical Cancer
A
- Findings can range from a normal appearing cervix with isolated abnormal cervical smear, to a grossly abnormal cervix that is replaced entirely with tumour.
- Any lesion that is raised, friable, or has the appearance of infection should be biopsed.
10
Q
Diagnosis of Cervical Cancer
A
- Diagnosis is confirmed with biopsies taken at colposcopy or examination under anesthetic + histological evaluation.
- CT or MRI can also be done to asses urinary tract and determine extend of the disease
11
Q
Treatment
A
- Treatment options are surgery, radiation, and chemotherapy depending on the stage of the disease, size of the tumour, and fitness of the patient.
- Radiotherapy can either be external photon beam radiotherapy or brachytherapy (insertion of radioactive implants directly into the tissues).
- With surgery, adjuvant radiotherapy or chemoradiotherapy is reccommended due to high rate of reccurrence and often close or positive surigcal margins.
- If cancer has spread, radiotharpy can be used for symptom management, including for metastatic disease.
12
Q
Route of Spread Cervical Cancer
A
- Cervical cancer can spread by direct extendion or by lymphatic or hematogenous dissemination
- Direct extension may involve uterine corpus, parametria, peritoneal cavity, bladder, or rectum. Ovarian involvement is rare.
- Hematogenous spread - lungs, liver, and bone. Less frequent sites include adrenal glands, spleen, and brain.
- Lymphatic spread - any of the plevic lymph nodes groups or even the para-aortic lymph nodes may contain the first draining lymph nodes and may be the first site of nodal metastasis.
13
Q
Melanoma
A
- Primary cutaneous malignant melanoma - cancer that arises from the melanocytes found in the basal layer of skin.
14
Q
Melanocytes
A
- Melanocytes - cells that produce melanin pigment and are responsible for producing tanning response after exposure to UV radiation.
15
Q
Melanoma Risk Factors
A
- Excess exposure to UV radiation
- High sun exposure in early childhood (before 10)
- History of sunburns
- Sunbathing hoildays
- Use of sunbeds - especially before 30
- Freckling
- Genetic susceptibility - CDKN2A
- Pale-skinned caucasion; red, blond hair
- Presence of naevi
- Immunosuppressive state
