USMLE® Step 1 style questions USMLE
A researcher is studying the molecular mechanism through which HPV infection leads to cervical cancer. He has developed an in vitro model that involves transfecting cervical epithelial cells grown in culture flasks with a lentivirus carrying the HPV E6 and E7 genes. The expression of protein E6 and E7 in infected cells is subsequently confirmed using fluorescence microscopy. Which of the following best describes the role these proteins play in the pathogenesis of cervical cancer?
Cervical cancer exam links
Contributors:Evan Debevec-McKenney, Salma Ladhani, MD, Robyn Hughes, MScBMC
Cervical cancer is a cancer of the female reproductive system that originates in the cervix.
It’s one of the most common cancers in women and it’s usually the result of an infection by the human papillomavirus, or HPV.
It has also played a huge role in scientific research thanks to cervical cancer cells from a woman called Henrietta Lacks, which were the first human cells to be grown in a laboratory and which continue to be used to this day in labs around the world.
The cervix is also called the neck of the uterus, and it protrudes into the vagina.
The interior cavity of the cervix is called the cervical canal and it can be divided into two sections.
The endocervix is closer to the uterus, not visible to the naked eye, and it’s lined by columnar epithelial cells that produce mucus.
The ectocervix is the continuous with the vagina and it’s lined by mature squamous epithelial cells.
Where the squamous epithelium of the ectocervix and the columnar epithelium of the endocervix meet, there’s a line called the squamocolumnar junction.
And right where the two types of cells meet, there’s the transformation zone - which is where sub-columnar reserve cells multiply and transform into immature squamous epithelium through a process called metaplasia.
Normally, mature cells are stuck in the G1, or Growth 1, phase of the cell cycle, which is when cells grow take care of regular cellular business, like synthesizing proteins and producing energy.
Eventually, whenever new cells are needed, they’ll exit G1 and keep going through the rest of the cell cycle to eventually divide in two new identical daughter cells.
Sometimes though, cells can be pushed out of G1 and go through the cell reproduction cycle faster than the body needs new cells.
This uncontrolled growth and multiplication is called dysplasia and it’s exactly how cervical cancer develops from precancerous cells.
Dysplasia in the epithelial layer of the cervix, also called cervical intraepithelial neoplasia or squamous epithelial lesion, usually starts in the basal layer of the transformation zone, typically in the immature squamous epithelium there.
In most cases, cervical intraepithelial neoplasia is caused by an HPV infection.
There are over 100 different types of HPV, but only about 15 of them have been linked with cervical cancer.
Specifically, HPV-16 is responsible for more than half of all cervical cancers.
The virus is like a house guest that overstays their welcome and starts using the kitchen to make all their favourite foods: it inserts itself into the immature squamous cells of the transformation zone and then integrates its DNA into the host DNA.
Using the host DNA, HPV makes huge amounts of two of its proteins, E6 and E7.
These proteins are responsible for pushing mature squamous cells through the cell replication cycle by blocking the action of tumor suppressor genes, like p53.
The end result is uncontrolled replication of cervical epithelial cells which are resistant to apoptosis, or normal programmed cell death.
Now, you might see a couple of different ways of describing the stages of cervical intraepithelial neoplasia, but the most common is based on how much of the epithelium is involved.
Grade 1 cervical intraepithelial neoplasia affects the lower one-third of the epithelium, thickness-wise.
Grade 2 affects two-thirds, Grade 3 affects almost all of the epithelium, and finally carcinoma in situ affects the entire thickness of the epithelium.
The higher the grade, the more likely the dysplasia will evolve into cancer.
Eventually, carcinoma in situ can progress to invasive cervical cancer, which is when cancerous cells break through the epithelial basement membrane and into the cervical stroma.
Then, it can spread to neighboring tissues, like epithelial layers of the uterus and of the vagina.
Finally, it can pass through the pelvic wall and affect the bladder and rectum.
Cervical cancer is a type of cancer that affects the cervix, which is the lower part of the uterus. The most common symptoms are vaginal bleeding and discharge. Other symptoms can include pain during sex, pelvic pain, and problems urinating.
Cervical cancer is caused by HPV (human papillomavirus), a sexually transmitted infection that can now be prevented by having an HPV vaccine. Screening tests can detect precancerous lesions on the cervix and get treated before they turn into cancer.
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