Cervical Cancer
Cervical cancer is the growth of abnormal cells in the lining of the cervix. This type of cancer is caused by persistent infection with the human papillomavirus (HPV). HPV is a common infection that passes through sexual contact. When exposed to HPV, the body's immune system typically prevents the virus from doing harm. In a small percentage of people, however, the virus survives for years. This contributes to the process that causes some cervical cells to become cancer cells. [1]
Anatomy Of Female Genital System
The organs in the female reproductive system include the uterus, ovaries, fallopian tubes, cervix, and vagina. The uterus has a muscular outer layer called the myometrium and an inner lining called the endometrium. The cervix has two main parts:
· The ectocervix or exocervix is the outer part of the cervix that can be seen during a gynecologic examination. It is covered with thin, flat cells called squamous cells.
· The endocervix is the inner part of the cervix that forms a canal that connects the vagina to the uterus. It is covered with column-shaped glandular cells that make mucus.
The squamocolumnar junction (also called the transformation zone) is the border where the endocervix and ectocervix meet. Most cervical cancers begin in this area.
The cervix is the lower, narrow end of the uterus that connects the uterus to the vagina. It is made up of the internal OS (the opening between the cervix and the upper part of the uterus), the endocervix (the inner part of the cervix that forms the endocervical canal), the ectocervix (the outer part of the cervix that opens into the vagina) and the external OS (the opening between the cervix and vagina).
Cervical cancer develops in the cervix, only a few centimeters away from the uterus, where uterine (body) cancer develops. Uterine cancer (endometrial carcinoma, womb cancer, or corpus carcinoma) usually originates from the cells of the uterine mucosa. The endometrium is the lining of the uterus, a hollow, muscular organ in a woman's pelvis. The uterus/womb is where a fetus grows. In most nonpregnant women, the uterus is about 3 inches long. Before cancer appears in the cervix, the cells of the cervix go through changes known as dysplasia, in which abnormal cells begin to appear in the cervical tissue. Over time, if not destroyed or removed, the abnormal cells may become cancer cells and start to grow and spread more deeply into the cervix and to surrounding areas. [2]
Types Of Cervical Cancer
The main types of cervical cancer are:
· Squamous cell carcinoma: This type of cervical cancer begins in thin, flat cells, called squamous cells. The squamous cells line the outer part of the cervix. About 80% to 90% of cervical cancers are squamous cell carcinomas
· Adenocarcinoma: This type of cervical cancer begins in the column-shaped gland cells that line the cervical canal. About 10% to 20% are adenocarcinomas and more difficult to diagnose because it starts higher in the cervix.
Global Statistics
Globally, some of the cancers that most often affect women are breast, colorectal, lung, cervical, endometrial, ovarian, and skin. Cervical cancer is the fourth most common cancer in women, with around 660,000 new cases in 2023. In the same year, about 94% of the 350,000 deaths caused by cervical cancer occurred in low- and middle-income countries. The highest rates of cervical cancer incidence and mortality are in Sub-Saharan Africa (SSA), Central America and South-East Asia. Regional differences in the cervical cancer burden are related to inequalities in access to vaccination, screening and treatment services, risk factors including HIV prevalence, and social and economic determinants such as sex, gender biases and poverty. Women living with HIV are 6 times more likely to develop cervical cancer compared to the general population, and an estimated 5% of all cervical cancer cases are attributable to HIV. Cervical cancer disproportionately affects younger women, and as a result, 20% of children who lose their mother to cancer do so due to cervical cancer.[2]
In May 2018, the World Health Organization (WHO) issued a call for the elimination of cervical cancer globally, and in November 17, 2020, WHO released the global strategy to accelerate the elimination of cervical cancer as a public health problem to light the road of cervical cancer prevention and control in future which mean that 194 countries promise together to eliminate cervical cancer by 2030. [3]
Risk Factors/Causes
Which may increase the risk of developing cervical cancer include:[4]
· HPV: This is a sexually transmitted virus. More than 100 different types of HPV can occur, at least 13 of which may cause cervical cancer.
· Having Many Sexual Partners Or Becoming Sexually Active Early: The transmission of cancer-causing HPV types nearly always occurs as a result of sexual contact with an individual who has HPV. Women who have had many sexual partners generally have a higher risk of HPV infection. Early age at first intercourse is another factor.
· Smoking: increases the risk of cervical cancer, as well as other types.
· A Weakened Immune System: The risk of cervical cancer is higher in those with HIV or AIDS, and people who have undergone a transplant, leading to the use of immunosuppressive medications.
· Birth Control Pills: Long-term use of some common contraceptive pills slightly raises a woman’s risk.
· Other Sexually Transmitted Diseases (STD): Chlamydia, gonorrhea, and syphilis increase the risk of developing cervical cancer.
· Socio-economic Status: Rates appear to be higher in areas where income is low.
Cervical cancer can be linked with known risk factors for the disease. Some risk factors can be avoided, while others cannot. Some risk factors within one’s control are:
· Screening History: Those who haven't had Pap tests (A Pap smear is a procedure that involves collecting cells from the cervix for testing. Also called cervical cytology and is used to look for cervical cancer) at regular intervals are at increased risk of cervical cancer.
· HPV Infection: Lowering risk also lower the risk for cervical cancer.
· Sexual History
· Smoking:
· HIV Infection: Those who've been infected with HIV have a higher-than-average risk of developing cervical cancer.
· Birth Control Pills
· Multiple Children: Having three or more full-term pregnancies may increase risk for developing cancer of the cervix.
· Having A Weakened Immune System: Having a weak immune system makes body unable to fight infections.
· Voluntary male circumcision.
· Safe Sex: Use condoms or other barrier methods when you have sex.
Some risk factors one can't change are:
DES (diethylstilbestrol): DES is a hormonal drug that used to be given to people between 1938 and 1971 to prevent miscarriage. If females have taken DES, they may be more likely to get cervical cancer.
Family History: Cervical cancer may have a genetic component.
Signs & Symptoms
Early stages of cervical cancer don't usually involve symptoms and are hard to detect. The first signs of cervical cancer may take several years to develop. Finding abnormal cells during cervical cancer screenings is the best way to avoid cervical cancer. [4]
Stage 1:
· Watery or bloody vaginal discharge that may be heavy and can have a foul odor.
· Vaginal discomfort, bleeding after intercourse, between menstrual periods or after menopause.
· Menstrual periods may be heavier and last longer than normal.
When Cancer Has Spread To Nearby Tissues Or Organs:
· Difficult or painful urination, sometimes with blood in urine.
· Diarrhea, pain or bleeding from rectum when pooping.
· Fatigue, loss of weight and appetite.
· A general feeling of illness.
· Dull backache or swelling in legs.
· Pelvic pain or pain during intercourse/abdominal pain.
Photo by National Cancer Institute on Unsplash
Early Detection, Diagnosis And Treatment Of Cervical Cancer
Clinical evaluations and tests to confirm a diagnosis are important and will generally be followed by referral for treatment services, which can include surgery, radiotherapy and chemotherapy as well as palliative care to provide supportive care and pain management.
Cervical Screening And Treatment Of Precancers
Women should be screened for cervical cancer every 5–10 years starting at age 30. Women living with HIV should be screened every 3 years starting at age 25. The global strategy encourages a minimum of two lifetime screens with a high-performance HPV test by age 35 and again by age 45 years. Precancers rarely cause symptoms, which is why regular cervical cancer screening is important, even if one has been vaccinated against HPV.[5]
Treatments of precancers are quick and generally painless causing infrequent complications. Treatment steps include colposcopy or visual inspection of the cervix to locate and assess the lesion followed by:
· Thermal ablation, which involves using a heated probe to burn off cells;
· Cryotherapy, which involves using a cold probe to freeze off the cells;
· Leetz (large loop excision of the transformation zone), which involves removing abnormal tissues with an electrically heated loop; and/or
· A cone biopsy, which involves using a knife to remove a cone-shaped wedge of tissue.
Tests To Check For Cervical Cancer
The tests used to detect cervical cancer are the Pap (Papanicolaou) Test and the HPV test or a combination. These cervical cancer screenings can find irregular or problematic cells in their earliest form before they have a chance to turn into cancer. Having an abnormal Pap smear is very common, so don't feel alone. It just means that additional tests are needed to prove that cervical cancer isn't present.[5]
When these cells are found early, cervical cancer is highly treatable and less likely to become serious. The healthcare provider performs Pap tests and HPV tests by using a brush to swab or scrape the cervix to collect cells. Once the swab is taken, the cells are put in a liquid and sent to a lab for testing.
Screening For Cervical Cancer
The goal of following cervical cancer screening is to detect cervical cells changes before they become cancer:
· Pap test: This test detects abnormal or irregular cells in cervix.
· HPV test: This test detects the high-risk types of HPV infection that are most likely to cause cervical cancer.
Diagnosis
Cervical cancer develops slowly and over many years. Before turning to cancer, the cells in cervix go through a lot of changes. The once normal cells in cervix start to appear irregular or abnormal, these abnormal cells may go away, stay the same or turn into cancer cells.
Regular gynecological screenings with a Pap test can detect most cases of cervical cancer. A Pap test, or Pap smear, is a test that collects cells from cervix. These cells are examined for signs of precancers or other irregularities. If Pap comes back as abnormal, further testing is necessary. This could include an HPV test, which is a specific test that checks the cells of cervix for HPV infection. Certain types of HPV infection are linked to cervical cancer. The healthcare provider may also examine cervix and take a sample of tissue for a biopsy if cancer is suspected. There are many techniques that can be used to obtain the tissue, like punch biopsy or endocervical curettage. In other cases, a wire loop or conization are used to gather tissues from the cervix for biopsy. [5]
If the biopsy confirms cancer, further tests will determine whether the disease has spread (metastasized). These tests might include:
· Liver and kidney function studies.
· Blood and urine tests.
· X-rays of bladder, rectum, bowels and abdominal cavity.
Routine Pelvic/Breast Examinations
If one is sexually active and under the age of 25, having annual screenings for chlamydia and gonorrhea may be recommended. Additionally, a clinical breast exam may help find lumps on breasts. The healthcare provider may decide to have a pelvic exam based on health history and sexual activity. It's still important to schedule routine care visits with healthcare provider to discuss sexual health and other concerns specific to reproductive health. Unlikely the self-breast examination, one won't feel cervical cancer with finger. Cancer cells are tiny and impossible to detect unless under a microscope. If one feels a bump or mass in vagina, it could be a sign of a polyp or cyst. Consult the healthcare provider right away if one feels a bump or lump inside vagina or breast. [5]
Prevention
Boosting public awareness, access to information and services are key to prevention and control of cervical cancer across the life course.[6]
· Being vaccinated at age 9–14 years before they become sexually active is a highly effective way to prevent HPV infection, cervical cancer and other HPV-related cancers. Currently there are 6 HPV vaccines available globally. All protect against the high-risk HPV types 16 and 18, which cause most cervical cancers and have been shown to be safe and effective in preventing HPV infection and cervical cancer. The vaccine may be given as 1 or 2 doses. People with reduced immune systems should ideally receive 2 or 3 doses. HPV vaccination may be given after pre-cancer or even after cervical cancer.
· Screening from the age of 30 (25 years in women living with HIV) can detect cervical disease, which when treated, also prevents cervical cancer.
· At any age with symptoms or concerns, early detection followed by prompt quality treatment can cure cervical cancer.
Treatment
Recommended treatment/therapy for cervical cancer is based on many factors including the stage of the disease, age and general health, and if one wants children in the future. The treatments for cervical cancer are radiation, chemotherapy, surgery, targeted therapy and immunotherapy.[6]
· Radiation: uses energy beams to kill cancer cells on cervix. There are two types of radiation therapy:
· External Beam Radiation Therapy (EBRT): Aims high-powered radiation at cancer from a machine outside the body.
· Brachytherapy: Puts the radiation in or just near cancer.
· Chemotherapy: Chemotherapy (chemo) uses drugs that are injected through veins or taken by mouth to kill cancer cells for killing cells anywhere in the body. Chemo is often given in cycles. The length of the cycle and the schedule or frequency of chemotherapy varies depending on the drug used and where cancer is located.
· Surgery: Some of the most common kinds of surgery for cervical cancer include:
· Laser surgery: uses a laser beam to burn off cancer cells.
· Cryosurgery: freezes cancer cells.
· Cone biopsy: a cone-shaped piece of tissue is removed from cervix.
· Simple Hysterectomy: involves the removal of uterus but not the tissue next to uterus including vagina and pelvic lymph nodes.
· Radical Hysterectomy With Pelvic Lymph Node Dissection: uterus, surrounding tissue called parametrium, cervix, a small portion of the upper part of vagina and lymph nodes from pelvis are removed.
· Trachelectomy: cervix and the upper part of vagina excluding uterus are removed.
· Pelvic Exenteration: same as a radical hysterectomy but includes bladder, vagina, rectum and part of colon, depending on where cancer has spread.
Sometimes a combination of treatments using radiation or chemotherapy to treat cancer that has spread or come back (recurred) may be used. The radiation and chemotherapy may be used before or after surgery.
· Targeted Therapy: Targeted drug treatment destroys specific cancer cells without damaging healthy cells. It works by targeting proteins that control how cancer cells grow and spread.
· Immunotherapy: Immunotherapy uses medicine to stimulate the immune system to recognize and destroy cancer cells. Cancer cells can also avoid being attacked by immune system by sending off a signal. Immunotherapy helps to target these signals so the cancer cells can't trick one’s body into thinking it's a healthy cell.
The prevalence of cervical cancer is still serious in less developed countries and regions, as effective preventive measures in these areas still face serious challenges. At present, there are various available prevention and control measures that are cost-effective. It is gratifying to note that the globe has achieved a strategic consensus on the elimination of cervical cancer and also has developed and released the global strategy to accelerate the elimination of cervical cancer. Although the global elimination of cervical cancer has a long way to go, it is believed that through large-scale continuous promotion and widely use of existing effective prevention and control measures, cervical cancer will become the first cancer eliminated by human beings.
Women living with HIV (human immunodeficiency virus, a virus that attacks the body's immune system) are more vulnerable for cervical cancers. If HIV is not treated, it can lead to AIDS (acquired immunodeficiency syndrome) which are 6 times more likely to develop cervical cancer. Prophylactic vaccination against HPV, screening and treatment of pre-cancer lesions are effective strategies to prevent cervical cancer and are very cost-effective. Cervical cancer can be cured if diagnosed at an early stage and treated promptly. Regional differences in the cervical cancer burden are related to inequalities in access to vaccination, screening and treatment services, risk factors including HIV prevalence, and social and economic determinants such as sex, gender biases and poverty. Cervical cancer disproportionately affects younger women, and as a result, 20% of children who lose their mother to cancer do so due to cervical cancer.
References
1. Crosbie EJ, Einstein MH, Franceschi S, et al Human papillomavirus and cervical cancer. Lancet. 2013;382:889–99. doi: 10.1016/S0140-6736(13)60022-7
2. Zur Hausen H Papillomaviruses in anogenital cancer as a model to understand the role of viruses in human cancers. Cancer Res. 1989;49:4677–81 Stelzle D, Tanaka LF, Lee KK, et al Estimates of the global burden of cervical cancer associated with HIV. Lancet Glob Health. 2020:S2214-109X(20)30459-9. doi: 10.1016/S2214-109X(20)30459-9.
3. Stelze, Dominik et al. Estimates of the global burden of cervical cancer associated with HIV. The Lancet. 2020. https://doi.org/10.1016/S2214-109X(20)30459-9
4. "Cervical Cancer Prevention and Early Detection". Cancer. Archived from the original on 10 July 2015.
5. "Cervical Cancer Symptoms, Signs, Causes, Stages & Treatment". medicinenet.com.
6. “Prevention of cervical cancer: what are the risks and benefits of different treatments ?".National Institute for Health and Care Research. 10 November 2023.