Cervical Cancer: Causes Of Disease And Diagnostic Tools

Cervical Cancer

Description and epidemiology

Cervical cancer is the most prevalent gynecological cancer among women, with 6.6% new cases reported in 2018. It is the 4th common cancer in women and 7th in all known cancers. Despite relatively easy treatment protocols existing, it is a common cause of death, especially in low income and development countries (Vaccarella et al., 2017) incidences being higher in sub-Saharan Africa, Southeast Asia, Latin America, the Caribbean’s and Central and Eastern Europe Experts suggest that the mortality attributed to cervical cancer can be reduced by applying comprehensive preventive measures, early diagnosis, and effective treatment and screening. Cervical cancer symptoms are usually late in presenting, prompting the need for regular pap smear tests. A pap smear is essentially not a test for cervical cancer but a checkup for cell state in the cervix. A small brush is used to obtain cells from the cervix and observed under a microscope. Cervical cancer is caused by irregular cell growth and division. This may be aggravated by

• The HPV virus that is sexually transmitted
• Multiple sexual partners. HPV is mostly transmitted via sexual interaction with men being carriers for HPV
• Smoking of tobacco
• Long-time use of birth control pills, over five years
• Coinfection with other sexually transmitted infections like herpes
• Parity and age at first birth

Other sexually transmitted diseases heighten the risk of developing cervical cancer

Cervical pre-cancer

This occurs in the cervix area called the transformation zone, where columnar cells are transformed into squamous cells. The presence of long term HPV infection triggers abnormal growth of cells. The appearance of cells is described and graded using the Bethesda reporting system for Squamous Intraepithelial Lesion (SIL), or alternative systems for cervical intraepithelial neoplasia (CIN)

Glandular cells may also exhibit abnormal observations; Atypical glandular cells(AGC) linked with anticipated cancer and adenocarcinoma in situ(AIS), which is pre-invasive cancer cells.

Screening

The aim of screening is to detect precancerous changes which, if untreated, may cause cancer. Women who exhibit cervical cancer symptoms need diagnosis and treatment to retreat cancer at early stages or curtail the development of cancer. According to WHO (2018), the possible modalities for cancer screening include: Screening should be done once for every woman whose age falls in the target age group (30-49) years. This is because screening is most beneficial at this stage. HPV testing, visual inspection, and cytology are recommended for tests for screening. Valuable approaches include ‘diagnose and treat, ‘screen and treat.’

Regardless of the strategy and the mechanism employed, the trick to effective intervention is to reach the largest population of women who are at risk with quality treatment and screening.

Comprehensive approach

It is recommended by WHO that successful control should encompass a comprehensive strategy to prevention and control, which includes a number of interventions through the life course: Social mobilization, community education, treatment, screening and palliative care, vaccination, screening, and treatment.

Physiology

Even though cervical cancer is not a sexually transmitted disease, it is linked to a sexually transmitted virus: the human papillomavirus. Survival rates are quite higher when the diagnosis is done early. Almost all cancer forms contain traces of the human papillomaviruses (HPV).Using the squamocolumnar junction or minor traumas as the access, the virus is said to infect the cervical epithelium cells. Two subtypes of HPV have been identified and include Low risk and high-risk HPV. Low risk HPV is associated with cutaneous infection like HPV 6, 11, 40, 42, 43, 44); and high risk is associated with genital tract infections (HPV 16, 18, 31, 33, 35, 45). Eighty percent of cervical cancers are due to HPV 45. As argued by Choma (2003), 75 percent of people who are within their reproductive ages have been infected with HPV. Young adults have suffered primary infection while a large percentage of people getting infected by the age of 30. The number of sexual partners has been found to be the primary factor that determines the acquisition of HPV. The HPV infection is transient and asymptomatic. Only 20 percent of those who tend to have premalignant lesions and just a small portion of these will develop into cancer. About 90 percent of infection gets resolved in two years. It is not clear if the virus is suppressed to levels that cannot be detected or if it is suppressed.

The only way to prevent HPV infection is to abstain from sex. It is due to this linkage with HPV that the disease is sometimes referred to as sexually transmitted infection. However, while HPV is sexually transmitted, the manner in which the malignancy develops is not.

Pathophysiology

Cervical cancer is capable of spreading throughout the body of a woman, especially the pelvic region and invades other tissues. Most of the symptoms that the disease causes occur due to the damage it does as it spreads (Healthline, 2019). Cancerous cells are capable of spreading throughout the lymph system. Firstly they move to the lymph nodes near the aorta or at the pelvis. These para-aortic and pelvic nodes are referred to as regional lymph nodes. They are the closest to the site that the cancer cells occur. From here, the cancerous cells can travel to different body parts. They can invade the liver and the body and can also affect the brain and the lungs. The complications that may occur due to invasive cancer include

• Back pain
• Pain during sex
• Fractures or bone pain
• Leakage of feces or urine from the vagina
• Loss of appetite and leg pain

Invasive cancer has a lower rate of survival compared to noninvasive cancer. Other than the effects that come by as a result of the disease itself, treatment of the condition can also come with a number of side effects. These effects can be more difficult to reverse than a treat. Before undergoing treatment, it is important that the side effects are discussed. Mounting evince suggests that genetic factors affect the susceptibility of an individual to HPV infection, which then influences their risk to develop cervical cancer. However, the involved genes and variants or mutations in those genes are yet to be fully established. Genetic susceptibility, just like in other cancers, might present as familial clustering of the condition.

Genetic influences

Research suggests that HPV is considered an exogenic risk factor for cervical cancer. Other predisposing factors include the use of oral contraceptives and smoking. These risk factors in their entirety may be shared within families due to possible shared lifestyles. Current research has not indicated whether familial clustered cervical cancer occurs significantly at an earlier age compared to sporadic cancer cervical cancer, which is taken as the basis of hereditary cancer. The estimations for heritability of cervical cancer have been said to be between 22% and 46 %. Because there are not many publications on familial clustering cervical cancer, there is the need to gather more data so that more precise estimations can be arrived at.

While a number of factors that contribute to the development of cervical cancer have been identified, most of which are intrinsic (genetic) and extrinsic (as a result of HPV), genetic factors have been declared to show the greatest potential for prognosis factors. Across the world, most association research for cervical cancer evaluates the single nucleotide polymorphism in the candidate genes, which form part of the cellular immune system as well as the oncogenesis. Mounting evidence has justified that there is a relationship between persistent HPV infection and cervical cancer and the existence of the evasion of the immune system (Martinez et al., 2016). Other studies have suggested that it is only a small population of women who are infected with HPV that ever develop cervical cancer and that a combination of host genetic, environmental, and viral factors are all determinants of the disease risks. A bigger proportion of susceptibility to the condition (greater than 70 percent) may not be due to additive genetic aspects; hence, it is essential to understand other contributing factors.

A study by Yang et al. (2018), suggests that genetic epidemiological research reveals that genetic factors significantly contribute to the carcinogenesis of cervical cancer. There are novel genetic mutations linked with the susceptibility of cervical cancer. Another study by Chambuso et al. (2018)., asserts that while no particular gene can be attributed to the increase, severity, or susceptibility of cervical cancer, several genes are indeed involved in varied molecular pathways. In most cases, cervical cancer is managed based on the stratification of the size of the tumor. Therefore, clinical presentations are based on traits and postoperative for chronic radiation enteropathy inpatient in need of surgery after received radical surgery (RRT) plus radiotherapy. The study found that more patients presented themselves with proctitis, perforation, and radiation-induced fistula in the RRT group. In the research, the most common surgical indication, and the most common symptom was radiation-induced digestive stenosis.

With regard to the obstruction site, it was found that the ileocecum/ileum was the most severely and frequently affected site. A number of past studies have depicted similar findings. Therefore it can be argued that the most severe and feared late toxicity is Fistula. Symptoms include persistent bleeding, leaking stool or urine, unbearable pain, venerability, psychological, social, and physical distress, which negatively affects the quality of life (Ntinga, & Maree, 2015). The late effects of the disease deprive women of the previous lives they lived. They become burdened with changes that interfere with their physical appearance and get aggravated by the difficult financial situations they have to live with. Cervical cancer causes sexual dysfunction during its late stages of development; sexual dysfunction has been known to interfere with intimate partner relationships, which causes anxiety resulting from the loss of life partners. In later stages, cervical cancer is known to cause emotional distress. Social lives and body image gets gravely affected by bladder and bowel effects. For example, they can experience unexpected bowel leakages.

Diagnostic tools

The first step in diagnosing cervical cancer involves conducting an abnormal pap test result. Further tests will result in the diagnosis of cervical cancer. Certain symptoms such as abnormal vaginal pain during coitus may also cause suspicion of the disease. The primary gynecologist or the doctor will always be able to conduct a test required to diagnose cancers and pre-cancer and may also be able to prescribe treatment for the pre-cancers.

Colposcopy

If some symptoms that may suggest the presence of cancer or when the results of the pap test reveal abnormal cells growth, there will be a need to conduct a Colposcopy test. This test involves the insertion of the speculum in the vaginal tract. This allows the doctors to examine the surface of the cervix clearly and closely. The process also involves the application of a weak solution of acetic acid on the cervix, making it easy to see. If lesions or abnormal areas are observed, tissues are extracted and sent to the lab for examination. The biopsy is the best way to tell if a site has true cancer, a pre-cancer, or neither.

Cervical biopsies

There is a number of biopsies that can be used as a means to diagnose cancers and pre-cancers. If the biopsy is able to remove all of the abnormal areas and tissues, the patient might not require any other treatment.

Colposcopic biopsy

For this kind of biopsy, a colposcope is used to examine the cervix to find the abnormal tissues. Using forceps, a small area of the abnormal region is removed. The procedure may cause brief pain, mild cramping, and light bleeding later on. Sometimes a local anesthetic is used to numb the cervix before the biopsy is done.

Endocervical curettage (endocervical scraping)

Sometimes the area that is thought to be at risk of pre-cancer or cancer may not be able to see using the colposcope, and another instrument has to be used (the curette) into the endocervical tract (the region nearest to the uterus). The work of the curette is to scrape the tissue, which is then taken for further examination in the lab.

Cone biopsy

This procedure which is also referred to as the conization, sees that the doctor will extract a cone-shaped tissue from the infected region in the cervix. The exocervic forms the base of the cone, and the apex comprises the endocervical canal. The areas between the endocervix and the exocervic form the transformational zone. It is in this zone that tissue is removed. This region has an area that is most likely to experience the infection. A cone biopsy can be used to remove many cancers and pre-cancers. There are two methods used in cone biopsy procedures and include cold knife cone biopsy and large loop excision of the infected area.

Loop electrosurgical procedure

In this strategy, the tissue is extracted using a thin loop of wire that is electrically heated and looks like a small knife. This technique requires the use of local anesthesia.

Cold knife cone biopsy

This technique is conducted in a hospital whereby a laser or a surgical scalpel is used to remove the tissue rather than using a wire. This procure requires the application of anesthesia for making the infected area numb (American Cancer Society, 2019).

Diagnostic tests

If the results from biopsies reveal the presence of cancer, there may be the need to conduct further tests to determine how far the spread has occurred. The tests include:

Cystoscopy, examination under anesthesia and proctoscopy

These are considered to be mostly done to women with tumors. Cystoscopy involves the insertion of a slender tube with a light and a lens through the urethra. This allows the doctor to see the walls of the urethra and the bladder to determine if the cancer is growing in those regions. This procedure allows the doctor to remove biopsy samples for microscopic examination.

Proctoscopy is the inspection of the rectum by the use of a lighted tube to examine the spread of cancer cells to the rectum. The doctor may also require a pelvic examination to determine if cancer has gone beyond the cervix.

Imaging studies

If the doctor finds that there are cancerous cells, there may be the need to conduct imaging studies. These tests can show the region where cancer has spread to thereby making it possible to recommend treatment. Chest rays, computed tomography, and Magnetic resonance imaging are all forms of imaging tests that are applied to determine the extent of the spread. Cervical cancer is treatable, especially if diagnosed early. The first thing is to determine the stage of cancer, which means finding out its spread to other parts and its size. A treatment is then recommended based on the stage.

The treatment for cervical cancer include

Radiation, chemotherapy, targeted therapy, and surgery. According to the American Cancer Society, the most crucial aspect in cervical cancer treatment is the stage of the treatment. For pre-cancers, the society recommends some types of colposcopy and pap tests as treatment options. Chemotherapy and radiation therapy are recommended treatments for stage 4 cancer.

Common areas for metastasis and prognosis

The common regions of distant mastitis of cervical cancer include the supraclavicular nodes, bones, lungs, and liver. The rare sites include muscles, brain, and other sites. Possibilities of distant metastatis and pelvic recurrence or both are high (Bhandari, Kausar, Naik, & Batra, 2016). The earlier the cancer is detected, the higher the chances of being treated with better outcomes. Early-stage cancers have high survival rates with good prognosis. If Cancer is detected after it has spread to other body parts, the chances of recurrence are high, and the prognosis is considered bad. The survival rate for cervical cancer is close to 100% when early changes are detected. Cancer patients in stage I have a survival rate of between 80-93% while those with stage II cervical cancer have a five-year rate of survival of between 58-63%

References

1. American Cancer Society (2019). Tests for Cervical Cancer | Diagnosed With Cervical Cancer. (2019). Retrieved 20 November, from https://www.cancer.org/cancer/cervical-cancer/detection-diagnosis-staging/how-diagnosed.html
2. Bhandari, V., Kausar, M., Naik, A., & Batra, M. (2016). Unusual metastasis from carcinoma cervix. The Journal of Obstetrics and Gynecology of India, 66(5), 358-362.
3. Cervical Cancer Complication: Metastasis and Treatment. (2019). Retrieved 20 November 2019, from https://www.healthline.com/health/cervical-cancer-complications#outlook
4. Chambuso, R., Gray, C. M., Kaambo, E., Rebello, G., & Ramesar, R. (2018). Impact of host molecular genetic variations and HIV/HPV Co-infection on cervical cancer progression: a systematic review. Oncomedicine, 3, 82-93.
5. Machalek, D. A., Wark, J. D., Tabrizi, S. N., Hopper, J. L., Bui, M., Dite, G. S., … & Garland, S. M. (2017). Genetic and environmental factors in invasive cervical cancer: Design and methods of a classical twin study. Twin Research and Human Genetics, 20(1), 10-18.
6. Martinez-Nava, G. A., Fernandez-Nino, J. A., Madrid-Marina, V., & Torres-Poveda, K. (2016). Cervical cancer genetic susceptibility: A systematic review and meta-analyses of recent evidence. PloS one, 11(7), e0157344.
7. Ntinga, S. N., & Maree, J. E. (2015). Living with the late effects of cervical cancer treatment: a descriptive qualitative study at an academic hospital in Gauteng. Southern African Journal of Gynaecological Oncology, 7(1), 21-26.
8. World Health Organization (2018). Cervical cancer. Retrieved 20 November 2019, from https://www.who.int/cancer/prevention/diagnosis-screening/cervical-cancer/en/
9. Yang, Y. C., Chang, T. Y., Chen, T. C., Lin, W. S., Lin, C. L., & Lee, Y. J. (2018). Replication of results from a cervical cancer genome-wide association study in Taiwanese women. Scientific reports, 8(1), 15319.