Cervical Cancer Flashcards
What are the features of cervical cancer?
It is one of the most common cancers in the world for women, and a major cause of death in the third world
Overall may cause 10% of all cancer deaths
Western countries typically have a lower incidence rate possibly due to the effectiveness of screening programs (though NZ has a higher than expected rate)
Has a low age (54) of onset reflecting the typical low age of the basal event
What are the features of the pathology of the cervix?
The cervix is exposed to mechanical, microbiologic, chemical and hormonal insults
Which is responded to by the cervix regularly being in a state of acute or chronic inflammation
Both cigarette smoking and HPV have being identified as important
Local wounding is required for HPV infection allowing HPV to bind to the basement membrane, infect basal cells and replicate
What is the transformation zone?
The squamous epithelium of the vagina meets with the columnar epithelium of the endocervix at a region known as the squamacolumnar junction, hormonal changes during puberty can cause repositioning of this junction toward the uterus this metaplastic change causes the region between the old and new junction to be known as the transformation zone
What is the natural history of squamous carcinoma of the cervix?
Columnar epithelium will change to immature metaplastic epithelium either due to the physiological response to changing hormones (in which case it will be typical, and undergo full maturation to and become invulnerable to carcinogenesis) or the action of carcinogens (in which case it will be atypical) which will cause the development cervical intraepithelial neoplasia leading to invasive cancer
What are the risk factors for cervical cancer?
HPV infection (which is linked to sexual intercourse at an early age, multiple male sexual partners or male sexual partners who have had multiple partners)
Smoking (this may be due to it being correlated to sexual behaviour, however nicotine metabolites have been seen in the cervical mucous)
Immunosuppression
Having children (this is a small risk factor and likely linked to cervical trauma during labour)
Oral contraceptives (these are controversial with some studies suggesting slight risk with long term use, and in vitro evidence showing that HPV transformation is enhanced by hormones, however there are confounding factors including individuals being less likely to use barrier contraceptives and increased screening among pill users)
Barrier contraceptives may slightly reduce the risk of cervical cancer
Age and access to screening programs are also risk factors
Why is cervical screening useful?
There is a long preclinical phase to the disease which allows for preventative screening which is simple and inexpensive
This can detect 90% of premalignant women
This has been shown to reduce the incidence of cervical cancer however no randomized controlled trials have been performed to document improved survival from screening
What is the procedure of the cervical smear?
Cells are collected using a spatula, cytobrush, thinprep, endocervical curettage and smeared onto a glass slide
A preservative is sprayed to prevent cells from drying and artifacts from forming
The accuracy of the smear requires an adequate sample, the presence of enough cells to show inflammation or dysplasia, quick fixation of the specimen to a glass slide
What are the recommendations for the frequency cervical smear tests?
Every three years for women over the age of 20 until they turn 70 if they have ever been sexually active
Normal screening interval is every 3 years however if this is your first smear or you haven’t had a smear for five years then another one is required in a years time
What is HPV?
Human papilloma virus which has a tropism for epithelial cells and is found in a variety of species and has over 200 distinct genotypes
What are the HPV types?
25 different types of HPV have been characterized that infect the male and female anogenital tracts and are capable of causing a broad spectrum of disease from benign condylomas to invasive squamous cell carcinomas
HPV 16 and 18 are the highest risk subtypes for cervical cancer, however other subtypes such as 45 and 31 have been implicated
Is cervical cancer the only HPV related cancer?
No, it has also been linked to cancers in the anus, vagina/vulva, penis, mouth and throat cancers
What is the time course of cervical cancer induced by HPV infection?
HPV has an initial infection with a normal cervix, there is a 50% chance that this will be cleared however this may develop to an HPV infected cervix, 20% of infections will then progress to a precancerous lesion and 30% of these will have this lesion become invasive leading to cancer
What are the low risk HPV types?
6 and 11 which are associated with condylomas or mild dysplastic changes in the cervical epithelium which do not typically lead to invasive disease
What are the high risk types of HPV?
16,18,31,33,35,39,45,51,52,56,58
What viral proteins from HPV can interact with human cells to causes disease?
E6 which can bind to p53 resulting in a loss of p53 actvivity by stimulating degradation by a ubiquitin-dependent proteolytic pathway (the E6 of HPV 16,18 has higher affinity for p53)
E7 which binds to the retinoblastoma gene product leading to dissociation of the E2F-RB complex which is important for DNA replication
