Rod Dunbar 3 Flashcards
How is cervical cancer treated?
It is largely preventable with early detection from pap smears and vaccines
Metastatic disease is also frequently treatable with radical surgery or combinational chemotherapy including platinum drugs and radiation
Why is the pap smear an effective way of treating cervical cancer?
It is highly effective as it can detect 90% of premalignant lesions and is simple and inexpensive
The disease has a long preclinical phase allowing for detection resulting in only a three year interval being needed between pap smears
What is the most common cause of cervical cancer?
Human papilloma virus which causes warts and has a trophism for epithelial cells
40 out of 120 subtypes are capable of genital tract infection with 15 being high risk for causing invasive carcinomas and 99.7% of women having one of these types
Is human papilloma virus the only thing required to cause cervical cancer?
No as 50% of unvaccinated sexually active women have an HPV infection and very few of these will get a cervical cancer (despite many carrying the high risk types)
Additionally many women can clear the infection, and precancerous infections have shown the ability to revert to normal
How is the cervix vulnerable?
It is continually bombarded with mechanical, microbial, chemical and hormonal signals with acute or chronic inflammatory reactions being relatively common
The transformation is likely especially vulnerable to carcinogens including potentially those from cigarette smoke or herpes simplex 2 infections
What is the transformative zone of the cervix?
The squamocolumnar junction between the squamous epithelium of the vagina and the columnar epithelium of the uterus
In puberty increasing levels of oestrogen cause a metaplastic changes of columnar to squamous epithelium causing this junction to be reposition further towards the uterus with the region between the old and new junction known as the transformative zone
What are the cell biology changes in cervical cancer?
Typically there is a dividing cell layer just above the basement membrane this is covered by several layers of well differentiated cells
In dysplasia most superficial cells are well differentiated but there are some proliferating cells seen far above the basal layer this is associated with low risk viruses like HPV6
In carcinomas the cells in all layers are proliferating and undifferentiated, this can become invasive if the basement membrane is breached
What HPV proteins play a role in cervical cancer formation?
E6 and E7 have multiple oncogenic properties however a key step of this effect occurring may be loss of the viral E2 gene which acts as a transcriptional repressor for E6,7 and is lost upon integration
E5 may also be oncogenic
HPV18 will always integrate while HPV 16 only sometimes integrates
What are the oncogenic properties possessed by E6 and E7?
E7 induces hyper proliferation through inhibition of Rb, and the p21/p27 inhibitors of CDK2 stimulating the parts of the cell cycle driven by cyclin A and cyclin E
However E7 on its own will cause cellular apoptosis, E6 can act to prevent this as it takes out p53 through increasing its degradation and preventing its acetylation by interacting with ADA3 and causing its degradation setting up genomic instability
E6 also targets the apoptotic effectors bax and bak for degradation and induces telomerase through the E6 associated protein
