What is cervical cancer?

Cervical cancer is cancer of the cervix, the lower part of the uterus that connects to the vagina. The cervix is divided in endocervix, which is closer to the body of the uterus and exocervix, which is closer to the vagina. The endocervix contains squamous cells and the exocervix contains glandular cells. Most cancers start in the area where these two cell types meet: the transformation zone. The cells lining the cervix develop pre-cancerous changes that are called cervical intraepithelial neoplasia (CIN), human squamous intraepithelial lesion (HSIL), and dysplasia, and can be detected under the microscope. Cervical Cancer is separated into squamous cell carcinoma, which affects the endocervix and makes up 80-90%, and adenocarcinoma, which develops in the exocervix. It can take several years before these changes can develop into invasive cancer, and not all pre-cancerous cells develop cancer as some go away on their own without any treatment. Once the cancer invades deep tissue and the cancerous cells break away from the main cell it spreads to other cells via the bloodstream or lymph vessels (American Cancer Society 2011).

Illustration of female reproductive system

93% of cervical cancer are caused by humanpapillomaviruses (HPV) (Bosch, et al. 1995). HPVs are the most common sexually transmitted infection and can cause genital warts as well as cervical cancer. However, the ones that cause cancer are different from those that cause warts (CDC). Even though the infection rate of HPV is 60%, most people clear the virus before the pre-cancerous HSIL can progress to a carcinoma and end in invasive cancer (Baseman and Koutsky 2005). There are about 15 out of 100 different HPVs associated with cervical cancer. And infection with oncogenic papillomavirus is considered a necessary but not sufficient cause for the development of cervix cancer (Burk, Chen, and Van Doorslaer 2009).

Risk Factors

Even though there is no clear evidence for why infection with human papillomavirus develops into cancer in some women, but not in others, several risk factors have been identified that are considered as increasing the chance of cancer development. It is important to notice that risk factors only suggest a correlation but not a direct causation for getting cervical cancer. The most common among these risk factors are:

• frequent change of sex partners (Baseman and Koutsky 2005) and unprotected sex as it increases the number of people one can get the disease from

• infection with certain types of HPV, such as HPV 16 and HPV 18 as they are seen as the main culprits in the development of the disease due to their strong persistence (Burk, Chen and Van Doorslaer 2009)

Graph about the distribution of prevalence (a), persistence (b) and progression (c) of oncogenic vs non-oncogenic HPVs in a population-based study of 100, 000 women from Costa Rica. It shows the importance of HPV 16 and HPV 18 presence as an indicator for cancer development.

• smoking as it makes the immune system less effective in fighting off the HPV virus (Baseman and Koutsky 2005) and because tobacco might be damaging the cervix cells (American Cancer Society 2011)

• use of oral contraceptives (Baseman and Koutsky 2005)

• a weakened or suppressed immune system as a result of AIDS, organ transplant or autoimmune disease (American Cancer Society 2011; Palefsky and Holly 1995)

• family history of cervical cancer can increase one’s chances by 2-3 times (American Cancer Society 2011). However, this is not because there is a genetic cause for the disease but rather because individuals with a certain genetic make-up might be less susceptible to HPV infections and others again display an enhanced ability to repair damaged cells ( He, et al. 2008)

• age over 50 for development of invasive cancer and age below 30 for HSIL (Baseman and Koutsky)

Symptoms, Stages and Treatment

Cervical cancer does not cause any symptoms early one. Unfortunately, most women don’t notice any changes until the cancer has already progressed. Once the cancer has advanced, individuals may experience vaginal discharge or irregular bleeding, especially after sexual intercourse (CDC 2011). Often this can take a very long time since years or even decades can lie between the onset of infection with HPV and the symptomatic phase of cervical cancer.

Treatment depends on the stage of the cancer, the woman’s age and her reproductive intentions.

In Stage IB: the most common procedure is a radical hysterectomy (removal of the uterus) with removal of lymph nodes in the pelvis. However, for women who still want to be able to have kids, the removal of the pelvic lymph nodes might be an option (American Cancer Society 2011).

In Stage IIB: suggested treatment is a combination of internal and external radiation with chemotherapy.

In Stage III: the lymph nodes have been infected by the cancer and most likely also to other areas of the body.

In Stage IVB: the cancer has spread to other adjacent areas like the pelvis and often also to the lungs and bones. Treatment is limited since at this point cervical cancer is not considered curable anymore. However, some doctors might still order chemotherapy to reduce the symptoms of the areas affected through spreading (American Cancer Society 2011).

Prevention

Cervical cancer is highly preventable through the use of primary and secondary prevention methods, with HPV vaccination accounting for primary prevention and Pap Smear as a secondary method of prevention (CDC 2011, Rohan and Sha 2004). There are two vaccines available for HPV (Gardasil and Cervarix), protecting against HPV 16 and HPV 18 and one of them also against HPV 6 and 11 (Wentzensen and Klug, 2009). Vaccinations are usually administered to 11-12 year old girls, or those between 13-26 who did not get any of the recommended three doses. Gardasil is also available for men (CDC 2011). However, being vaccinated against these types of HPV does not mean that one cannot develop cervical cancer. Even though, the highest percentage of cervical cancer is caused by HPV 16 and 18, there are at least 13 other HPV types that are associated with increasing the risk for cancer. Consequently, vaccinations alone are not a cure, but a good start.

Therefore, secondary methods of prevention, such as Pap smear and HPV tests are important. Cervical cancer develops over time with the building of precursor lesions. Some lesions regress on their own, while others progress to a malignant stage. The purpose of “screening is to detect the lesions that have a high risk of progression (into cancer)” (Wentzensen and Klug, 2009), so that individuals can get treatment right away. A Pap smear is utilized for this kind of screening. The doctor takes a smear of the endocervix and exocervix part of the cervix and examines it under the microscope for abnormal cell development (Wentzensen and Klug, 2009). If precursor lesions with a high risk for progression are found, they are removed in order to prevent the development of cancer. However, it is not enough to just have one Pap smear test, as some tests can show up as false negative or positive, respectively, Thus, it is important to repeat Pap smears frequently to guarantee reliability. With a frequently repeated Pap smear, the chances of cancer are close to zero.

Another valuable and more reliable screening method is the HPV DNA test as it detects the presence of the virus. However, one problem with this type of test is that it does not separate between transient infections and the ones that progress into cancer.

Rohan and Sha suggest in their book Cervical Cancer: From Etiology to Prevention (2004) that the development of cervical cancer could be prevented through chemoprevention, which is a process that uses “drugs or other agents in order to inhibit, delay or reverse the progressive genetic damage and the associated tissue damage that accrue during carcinogenesis”.