Cervical Cancer

Cervical cancer is very common in women worldwide. It is the third most common malignancy in women and affects women in both the developing world as well as in developed countries. While the rate of HPV cervical cancer has diminished in the United States over the past several years, likely due to the utilization of HPV vaccines; which prevents HPV infection, a known cause of cervical cancer, it is still a preventable malignancy that affects many women.

Pathophysiology


There are two major types of cervical cancer: squamous cell carcinoma and adenocarcinoma.


The most common type of cervical cancer is squamous cell carcinomas. Squamous cell carcinomas develop from squamous cells, which are thin in nature and line the outer portion of the cervix. Adenocarcinoma, on the other hand, is a glandular form of cancer that develops from columnar cells that line the canal of the cervix.

The majority of cases of cervical cancers are caused by the Human Papillomavirus (HPV). This virus occurs in nearly all women who are sexually active, but is usually self-limiting. It is only in a few percent of the patient population exposed to this virus that cervical cancer will develop. The other form of cervical cancer, which is less prevalent when compared to cervical cancer caused by HPV, results from smoking. Smoking is a huge risk factor for a variety of cancers in a variety of anatomic locations within the body, and cervical cancer is no exception.


Cervical cancer that results from the HPV virus is dependent on a host of factors. The major factors that contribute to the resultant development of cervical cancer from HPV include:  strain type of the virus (certain HPV strains are more carcinogenic than others), compromised immune system, smoking and vitamin deficiencies.  Patients who become sexually active at an early age and/or have increased number of sexual partners also face a higher risk of developing cervical cancer in the future. There have also been studies that have indicated a that there is a genetic component to the development of cervical cancer from HPV infection. Studies have suggested that women who have a family history of a first degree relative being diagnosed with cervical cancer are at increased risk (as much as 100% more) of developing cervical cancer at some point in their lifetime; as compared to those who did not have a family history of any first degree relative with cervical cancer.
 

The HPV virus is composed of double-stranded DNA composed of 6 major regulatory proteins:  E1, E2, E3, E4, E6 and E7; and two frame proteins L1 and L2.  There are over one hundred different strains of the HPV virus. However not all of those strains result or even predispose
one to the development of cervical cancer.  When patients with cervical cancer were evaluated, it was found that approximately 8 strains were the cause of cervical cancer.  The high risk strains that are the most common contributors to the development of cervical cancer include:  HPV type 16, 18, 31, 33, 35, 45, 52 and 58; with HPV type 16, 18 and 45 being the most common viral strains resulting in Cervical Adenocarcinomas.  There are other HPV strains that are considered low risk and must be evaluated accordingly – to ensure that further development of less invasive, low-grade cancers are not present.


When the patient becomes infected with the HPV virus, the viral proteins begin to bind to proteins present within the body. For example, E7 binds to a protein called Rb protein, which results in its inactivation. E6 binds to p53 and breaks it down, causing Tp53 and Rb genes to lose their original function, which is to mediate apoptosis. Without mediation of apoptosis, there is an overproduction of cell growth after DNA is damaged. The uncontrolled cell replication results in mutated, cancerous cells that progress into cancer.


Patients who are immunodeficient because of certain diseases are at increased risk of developing viruses such as HPV that may progress to cervical cancer in the future. One major immunity compromising virus that can increase the risk of being infected with HPV is another sexually transmitted virus HIV (Human Immunodeficiency Virus). Studies have suggested that patients with HIV are 5 times more likely to contract HPV, that may progress to malignancy.

Symptoms & Risk Factors for cervical cancer:

It is imperative to be proactive and be evaluated by an OB/Gyn on a yearly basis, so
that appropriate testing for cervical cancer can be performed. This is because early
symptoms associated with cervical cancer are usually minimal to none.  

Signs and symptoms that may occur later in the disease include:  

  • post-coital vaginal bleeding
  • vaginal bleeding after menopause
  • vaginal bleeding between periods
  • bloody vaginal discharge with a foul odor
  • increased heavy vaginal bleeding
  • pelvic pain
  • dyspareunia (pain during sex)


Risk Factors:

There are risk factors that increase one’s potential for developing HPV infections and thus cervical cancer.

  • Hispanic women are at the highest risk of development of cervical cancer as compared to women of other races.
  • Asian/Pacific Islander women have the lowest risk of developing cervical cancer as compared to other women.
  • Women who have multiple sexual partners and/or begin having sex at a young age face increased risk of developing HPV infections.
  • Being infected with other STIs can also increase the chance of being infected with HPV.
  • Being immunocompromised, or being a smoker, are also risk factors that can contribute to increased risk of HPV contraction.

Diagnosis & Stages of Cervical Cancer:


Early diagnosis of cervical cancer is imperative for better prognosis.  Because the early stages of cervical cancer are  not associated with signs/symptoms, it is imperative that screening tests be used to catch early stages of cervical cancer.  Women should begin screening for HPV infection and cervical cancer when they are 21 years of age. This age may vary depending on the patient’s risk factors, including their number of sexual partners and the age at which they began having sex.


The first screening test is the pap smear. The pap smear is when the OB/Gyn physician uses a speculum to visualize the cervix, and then uses a medical instrument to brush or scrape some of the cells from the cervix. These cells are then sent to the laboratory and evaluated for any abnormalities. The pap smear will check for cancerous cells of the cervix. The next test is the HPV DNA test. This test checks for the actual HPV virus. The cells collected from the cervix will be evaluated for the HPV DNA. This test is done in women greater than the age of 30 or in patients who currently have, or who have a previous history of, an abnormal pap smear.


If the pap smear and/or HPV DNA test comes back abnormal, the next step in diagnosis is through a colposcope evaluation. During this examination the physician will likely take a biopsy to determine if cervical cancer is present. Biopsy can be in the form of a punch biopsy or an endocervical curettage. If these tests come back abnormal, then the next step is to perform either an electrical wire loop tissue sample or a cone biopsy, that will allow for better evaluation of the deeper layers of the cervix. The tissue will be evaluated at the laboratory to determine
if cervical cancer is present.

Stages of cervical cancer:

In patients who have a positive biopsy for cervical cancer, the next step is to determine the stage of the cancer.  Staging is based on tumor size, nodal involvement and metastases to other areas of the body. There are four stages of cervical cancer.  



Stage 0 is the least invasive and has the best prognosis, and Stage IV is the most invasive with the poorest prognosis. Stage 0 is Carcinoma In Situ and is not invasive.  


In Stage I cervical cancer, the cancer is located only in the cervix.  


Stage II means that the cancer is present in the cervix and the upper section of the vagina.  


Stage III cervical cancer means that the cancer has moved from the cervix and upper section of the vagina to the lower section of the vagina or internally to the pelvic side wall.  


Stage IV cervical cancer means that there is involvement of other near organs such as the rectum or bladder. Stage IV can also mean distant spread of the cancer to (most commonly) liver, lungs and/or bone.

Treatment & Prognosis of cervical cancer:


Treatment:

An individualized treatment plan must be developed based on one’s own medical history and staging of the cancer. Most interventions include: surgery, radiation and/or chemotherapy. 

Stage 0 cancer is treated with either cryosurgery, laser ablation or loop excision. In early stages of cancer, mainly Stage I, surgery is the standard of care. Hysterectomy can actually be the cure of early Stage I cervical cancer, as well as prevent recurrence. Discuss with your physician if you require a Simple Hysterectomy or a Radical Hysterectomy.


Radiation therapy may be indicated in Stage I cervical cancer. It will be based on medical history, and personal evaluation by your physician. For Stages IA2, IB or IIA cervical cancer there are two treatment options available: combined external beam radiation with brachytherapy and radical hysterectomy with bilateral pelvic lymphadenectomy.  For Stage IIB, III or IVA, the recommended therapy is external beam radiation to decrease tumor size, and then brachytherapy. Research and clinical studies have shown that combination chemotherapy has dramatically improved patient’s’ chances of survival.  For Stage IVB and recurrent cancer, individualized therapy and palliative therapy will be recommended based on the individual case.


Prognosis:

The prognosis of patients with cervical cancer is based on  5 year survival rates. Stage I has a prognosis of greater than 90%. Stage II has a prognosis of 60-80%. Stage III has a prognosis of approximately 50% and Stage IV has a prognosis of less than 30%.


It is imperative to remember that you are an individual and not a statistic. While statistics offer insight into the patient population, each individual is unique and thus these statistics will not apply to everyone. It is imperative that early diagnosis is done, so that each patient has the best chance of survival.


Cervical cancer can be a devastating diagnosis. However, it is a type of malignancy that can be prevented and treated with early diagnosis. Therefore, it is imperative to follow up with your OB/Gyn and be screened annually. Speak with your healthcare provider to determine the most appropriate treatment plan for your individual case.

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