Cervical cancer

Cervical cancer begins with infection with HPV (human papilloma virus) that stimulate behavioral
changes of cervical epithelial cells. These mutated cells that perform uncontrolled division, immortal
and invade the underlying stromal tissue. HPV infection and other conditions like sexual behavior,
contraception, or smoking will increase the susceptibility to cervical cancer. The mechanism of the
onset of cervical cancer is a complex process and very varied that it is difficult to understand. The
incidence and mortality of cervical cancer in the world second only to breast cancer.

Other factors associated with cervical cancer is sexual activity too young (<16 years), the number of
couples sekual high (> 4 people), and a history of infection berpapil (warts). Due to our close
relationship with HPV infection, women who receive or use of immunosuppressant
(immunosuppresive) and patients with HIV are at risk of cervical cancer. Tobacco specific
carcinogens found in her cervical mucus of smokers. These can damage DNA and squamous epithelial
cells with HPV infection trigger malignant transformation.

The role of HPV (Human Papilloma Virus)

HPV Virus includes family papovirus ie a DNA virus. This virus infects the basal membrane in the
region and the transformation of cervical metaplasia. After infects cervical epithelial cells in an
attempt to reproduce, the virus will leave the host cell genome. Episomal form of HPV genome,
which is circular in shape and are not integrated with the host DNA found in CIN and integrate with
host DNA in invasive cancer. In vitro experiments with HPV proven to transform cells to become
immortal.

Today, HPV infection tends to increase and continued efforts to identify the type of virus. From the
results of the different DNA sequences, until now, has been known for more than 200 types of HPV.
Most HPV infections are benign. Thirty of them are transmitted through sexual contact with each
changing ability of cervical epithelial cells.

Low-risk types such as types 6 and 11 associated with condyloma and mild dysplasia. Conversely,
high-risk types such as types 16, 18, 31, 33, and 35 associated with moderate dysplasia to carcinoma
in situ. The relationship between HPV infection to cervical cancer was first instigated by Harold zur
Hassen in 1980. The relationship between HPV infection to cervical cancer appears to be much
stronger when compared with smoking and lung cancer. Infection occurs through direct contact. The
use of condoms is not secure enough to prevent the spread of this virus because condoms only cover
most of the genitals just as labia, scrotum and anal area unprotected. High-risk types of the virus
produces a protein known as E6 and E7 proteins are able to bind and deactivate proteins p53 and PRB
cervical epithelium. P53 and PRB is a tumor suppressor protein that plays a role in inhibiting the
survival of the cell cycle. With no active p53 and PRB, cells that have mutated due to HPV infection
can pass the cell cycle without having to repair its DNA abnormalities. E6 and E7 bond seta DNA
mutation is the main basis of cancer.

More than 90% of cervical cancers contain viral DNA squamous types of HPV and 50% of cervical
cancer associated with HPV type 16. Of the many types of HPV, types 16 and 18 have an important
role for the E6 and E7 gene sequences with mengode formation of proteins that are important in viral
replication. E6 oncoprotein of will bind and make the tumor suppressor gene (p53) becomes inactive,
whereas the E7 oncoprotein binds and makes the retinoblastoma gene product (PRB) menjad inactive.

Symptoms and signs

Lesions of cervical cancer very early cervical intraepithelial neoplasia known as (cervical
intraepithelial neoplasia) are characterized by the presence of dysplastic changes in cervical
epithelium. Rate of growth of different cancers in one case and the other cases, but the mechanism is
unclear. The earlier the disease can be identified and given adequate therapy, the results were perfect.
Despite the invasion of tumor cells into the stroma, cervical cancer may not cause symptoms still.
Early signs of cervical cancer are not specific as there are rather a lot of vaginal discharge and
sometimes with patches of bleeding. Generally, the sign is still very least ignored by the patient.

The more classic signs are spotting recurrent bleeding, spotting or bleeding after intercourse or
cleaning the vagina. Increasingly growing disease, signs and symptoms more clearly. More bleeding,
more frequent and lasts longer. Can be found also smelling vaginal discharge mainly due to necrosis
of mass information. Necrosis occurs due to rapid tumor growth is not matched the growth of blood
vessels (angiogenesis) that does not receive enough blood flow. This raises the unpleasant smell and
non-specific inflammatory reactions. In later stages, the tumor has spread beyond the cervix and
involving tissue in the pelvic cavity can diumpai other signs such as pain that radiates to the hips or
legs. This indicates the involvement of the ureter, pelvic wall, or sciatic nerve. Some patients
complain of pain in urination, hematuria, rectal bleeding, it was hard to urinate and defecate. The
spread to the lymph nodes can cause edema of the lower leg lower leg lower leg, or a blockage of both
ureters.

PAP TEST
Papapanicolau test or better known as the Pap test is a simple procedure to check for potential signs of
cervical cancer in women. The procedure is named after the inventor of potentially abnormal cells of
cervical cancer in 1928, dr. Papanicolau. Pap test is done not for the purpose of diagnosis but to detect
any changes that may lead to cancer. (6) Currently, there are two types of cervical cytology techniques
that can be used, they are the conventional Pap screening and liquid-based cytology (LBC).
EXAMINATION REQUIREMENTS
Pap test done when the patient is not in a state of menstruation. The best time is 5 days after
menstruation stops. Patients were also not allowed to have sexual intercourse, vaginal rinse with
various liquid chemicals, using drugs that is inserted into or dab around the vagina for at least 24 to 48
hours before the examination. Examination should not be performed if there is inflammation or
unexplained bleeding as these symptoms may be caused by cancer in the genital area.
Complete clinical information, including the date of last menstrual period and pregnancy, use of
hormonal medications, menopausal status, and history of bleeding or abnormal pap screening results,
are necessary for an accurate interpretation of Pap screening. The use of intrauterine devices that can
cause cellular changes should also be noted. Having immunosuppresive condition or have never been
Pap screened are the risk factors to be noted that may assist in interpreting the results.
Direct contact with the cervix should be avoided before the Pap test so the epithelium which
undergoes displasia and severe lesion can be removed with minimal trauma. Secretions covering the
cervix can be carefully cleaned using a swab without touching the cervix.

LOCATION
Sampling of the transformation zone is important for the sensitivity of Pap tests. The technique must
be adapted and a suitable tool should be chosen according to the location of the squamocolumnar
junction which varies with age, obstetric trauma, and hormonal status. Women suspected to DES
(diethylstilbestrol) in utero exposure is recommended for a separate pap test with samples from the
upper vagina as ther are more at risk for vaginal cancer.

TOOLS
There are 3 kinds of tools that are usually used to take a sample of the cervix: a spatula for
ectoservical sampling, endocervical brush to take samples from the endoservical canal and is usually
combined with the use of a spatula, and the broom to take the sample of the endo- or ectoservical
epithelial. Spatula is made according to the shape of the opening of the cervix so as to facilitate the
opening of squamocolumnar junction to take samples from the distal endoservical canal. Plastic
spatula is more preferred than a wooden one since cells are more easily removed from the plastic
surface. Endocervical brush has a conical shape with plastic bristles that can collect and release
endocervical cells better than moistened cotton swab. Once the spatula sample is obtained,
endocervical brush is inserted into the endocervical canal only until the outermost bristles remain
visible to avoid taking cells from the lower uterine segment unintentionally. To avoid excessive
bleeding, brush is rotated only a quarter to a half turn. If the cervical canal is wide, as in women who
have given birth, the brush is moved so that it comes in contact with the entire surface of the
endocervical canal. Broom device has the longest central feathers incorporated into endocervical
canal. These longer bristles is lined by shorter bristles which will widened out and sweep the
ectocervical surface when rotated clockwise in a few turns. Recommended number of broom rotation
varies depending on the manufacturer. Broom tool is usually used for LBC.

CONVENTIONAL PAP SCREENING (PAP SMEAR)

Cytologic method requires special care to prevent drying cells that can degrade the quality of the
tested slide. Spatula samples must be handled while endocervical brush samples is taken. The spatula
samples must then be be smeared as evenly as possible on glass slide. Endocervical brush samples
will then be rolled on the remaining part on the slide, after the fixation is done by spray or immersion.

LIQUID-BASED CYTOLOGY (LBC)

Imperfect sensitivity and the quality of the smear that varies from conventional pap preparations have
driven the development of thin-layer liquid-based cytology (LBC) during the last decade. LBC
method to collect cells in liquid transport medium are further processed to produce single-layer cell
smears spread evenly on a glass slide. There are currently 2 LBC products marketed in the United
States: SurePath and ThinPrep. Both of these products have been approved by the FDA (Food and
Drug Administration) as an alternative to the conventional Pap test.
The number of cells, between 50,000 and 75,000, and the area of slide covered is less than in
conventional smear. However, obscuring blood, mucus, debris, and the overlapping cells are largely
eliminated. In theory, the abnormal cells which may be few in number, clustered and appear blurry on
conventional smears will be scattered randomly and evenly on LBC slides making it easier to detect.
In addition, most of the collected cellular materials are available for processing in the laboratory and
are not removed in the sampling process.
Residues of LBC specimens can be included in the test for HPV, herpes simplex virus, Neisseria
gonorrhoeae and Chlamydia trachomatis.
Sampling and transfer of cells into the liquid media shall be done in accordance with the
specifications of the tools used. SurePath tool uses three types of tools with modified device tips that
can be broken off and can be sent to a laboratory in liquid media. ThinPrep requires immediate and
vigorous agitation of the selected sampling device in a liquid medium. The tool is discarded after use.