Cervical cancer & intraepithelial neoplasia – causes, symptoms, diagnosis, treatment, pathology

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much more. Try it free today! 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 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 and 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
into 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 a 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. Lastly, it can also spread via the lymphatic
and circulatory systems to other areas of the body like the liver and lungs. Because HPV tends to invade squamous cells
first, the majority of cervical cancer cases are squamous cell carcinomas. The second most common type, also associated
with HPV, is cervical adenocarcinoma, which involves the epithelial gland cells of the
cervix. But either way, the progression from HPV infection
to cervical intraepithelial neoplasia to cancer is generally slow and it can take between
10 and 20 years before invasive cervical cancer develops. Ok, now, since HPV is a sexually transmitted
infection, the risk of developing cervical cancer is highest in females who do not use
condoms and have multiple sexual partners. Not every HPV infection results in cervical
cancer, though. In fact, the immune system fights off most
HPV infections. So it’s believed that there are other factors
involved. For example, the risk increases depending
on the type of HPV, how long the infection lasts, and if the person is immunocompromised. Environmental factors like smoking also increase
the risk. But the good news is that vaccination against
HPV immunizes against several HPV types linked with cervical cancer, including HPV-16. The first symptom of cervical cancer is often
abnormal vaginal bleeding, especially after sexual intercourse. Other symptoms include vaginal discomfort,
vaginal discharge with an unpleasant smell, and pain when urinating. If the cancer has spread beyond the pelvic
wall, it can cause symptoms like constipation and bloody urine. Screening for cervical intraepithelial neoplasia
and cervical cancer is done with a Pap smear with high-risk HPV testing. Pap tests are so good at detecting precancerous
cells that screening recommends a pap smear every 3 years for females between 21 and 65
years of age. Together with the HPV vaccine, this has contributed
significantly to the drop in cases of cervical cancer worldwide. Now, during a Pap test, some cells from the
transformation zone are collected with a brush and then they’re examined under a microscope
for dysplasia. If the Pap test comes back positive for dysplasia,
it may be followed up with a colposcopy, which is when a magnifying device called a colposcope
is used to get a zoomed in view of the cervix, and then obtain biopsies. Treatment options for cervical intraepithelial
neoplasia include cryosurgery, where liquid nitrous oxide is used to freeze and kill abnormal
cells, and conization, where the transformation zone and some or all of the endocervix is
removed surgically. Conization can be done with a scalpel, called
cold-knife conization, laser, or by heating a loop of thin wire with electricity, called
loop electrosurgical excision procedure or large loop excision of the transformation
zone. Treatment of early cervical cancer is to surgically
remove either just the tumor, or also the uterus and associated lymph nodes. If the cancer is more advanced, radiation
and chemotherapy may be done. All right, as a quick recap… Cervical cancer is a cancer of the female
reproductive system affecting the cervix. It’s most often a squamous cell carcinoma
caused by a human papillomavirus infection. It starts as cervical intraepithelial neoplasia
and develops very slowly. Many cases of cervical cancer can now be prevented
thanks to the HPV vaccine, or caught very early on by screening for precancerous lesions
with a Pap test. Precancerous lesions can be managed with cryosurgery
or conization, whereas treatment for cervical cancer is surgical.