Cervix is a narrow part of the uterus that connects vagina to the uterus. Every year more than 13,000 women in the United States develop cervical cancer. Cancer of cervix is the 4th most common cause in women worldwide, despite the presence of highly advanced treatment and screening methods.
The most significant reason for predisposition of the cervix towards cancer is high cell turnover in the transformation zone. This area is characterized by constant epithelial shedding and differentiation of basal and parabasal cells to replace the old epithelial layer. Cervical Intraepithelial Neoplasia is the pre-malignant condition of cervical cancer which can be diagnosed with pap smear. It has 3 stages with different characteristic feature. With each passing stage, risk of cancer increases. Cervical cancer occurs when the abnormally growing cells attain the ability to invade the stroma of the cervix.
There are several causes that increase your chance of developing cervical cancer. Women who are not exposed so such causes rarely develop cervical cancer. Although these risk factors increase the probability of developing cervical cancer, many women exposed so these causes do not develop cervical cancer in their life. When a woman develops cervical cancer or pre-malignant changes, it is difficult to point out the cause of cervical cancer. Screening is an important step to prevent the incidence of cervical cancer.
What causes cervical cancer?
Human papillomavirus (HPV) infection
Research reveal that HPV (human papillomavirus) is single most important cause of cervical cancer. HPV is a group of 100 related viruses that can cause infection of the skin. genitals, mouth and throat. Few types cause genital warts and are known as “low risk” types. Other types have strong association with cancer of the cervix. They are “high risk” types. HPV 16 and 18 are considered as high-risk types.
Skin-to-skin contact during vaginal, anal, or oral sex is major mode of transmission of HPV. But sex isn’t the only way to transmit HPV. Studies are being done to confirm vertical transmission of HPV i.e. in utero, intrapartum or postpartum. In most cases, the body’s immune system eradicates the virus and the infection goes away. In some cases, the infection lasts and eventually contribute in developing cervical cancer.
Young women are major victim of cervical cancer and it is far less common in women over 30. Condoms are advised by the doctors in order to prevent the transmission of HPV infection from person to person. Women who start having sex at a young age are more prone to be infected with HPV. Multiple sex partners also increase the likelihood of getting an HPV infection. The Pap test is the best possible way to detect any malignant or pre-malignant cell changes. Few other tests try to find out the infectious agent itself by detecting DNA from HPV in the cells. HPV is incurable but the abnormal cell growth can be controlled. Vaccines are discovered that can prevent infection with some types of HPV.
HPV is known to infect of basal or para-basal cells. The next step in the life cycle is replication of its own DNA during basal cell differentiation resulting in amplification of its DNA. Capsid proteins are synthesized in the differentiated keratinocytes. Viral particles are assembled in host’s nucleus. Persistent infections are linked with incorporation of the viral genome into the host genome. The HPV life-cycle is controlled by few viral proteins. Significant viral proteins that control HPV life cycle are HPV E6, E7 and E2 proteins. These two proteins are synthesized early in the viral life cycle and are particularly helpful in downgrading the cellular growth of the host. They bind with several tumor suppressor proteins, cell cyclins, and cyclin-dependent kinases subsequently inactivating them. The tumor suppressor protein p53 and the retinoblastoma gene product pRB are inactivated by E6 and E7 proteins respectively.
Women who are exposed to smoke are about twice as likely to develop cervical cancer as those who don’t. Harmful substances in smoke are passed in the blood which transfers it to all parts of the body. Research has revealed that tobacco by-products are present in the cervical mucus of women who are exposed to smoke. Smoking also weakens immune system of the body which eventually fails to fight off HPV infections.
HPV cannot be considered as a sole culprit for cervical cancer. The roles of other potential causes in pathogenesis of cervical cancer is being studied. An increased risk of cervical cancer associated with tobacco smoking has been found in number of studies. Genotoxic DNA adducts of smoking in the cervix epithelium eventually leading to development of cervical cancer is the widely accepted theory. Weakening of immune system and local immunosuppression subsequently leading to high risk of HPV infections has also been discussed A number of studies only limited to HPV positive women have revealed an amplified risk for cervical cancer in smokers compared with non-smokers.
Weakened immune system
HIV (human immunodeficiency virus) is the virus that is responsible for causing AIDS. HIV-infected women are more prone to develop cervical cancer. Having HIV weakens immune system of the person resulting in decreased ability to fight off HPV and early cancers.
Women on immunosuppressive drugs are more prone to develop cervical cancer. Corticosteroid medications, organ transplantation, treatments for other types of cancer can decline the function of immune system in the body resulting in increased risk of being infected with HPV infections. Routine screening for cervical cancer in developed countries has decreased incidence of cervical cancer.
Large number of genital infections in women are caused by Chlamydia. It is also transmitted by sexual intercourse. Pelvic examination has to be done to find out the presence of organism in women’s body. Some studies have revealed that women who have a past or current infection are more prone to develop cancer of the cervix.
Research found that presence of C. trachomatis antibodies is linked to higher risk of developing cervical cancer. They implied that infected patients are more than twice as likely as to develop cervical cancer than non-C. trachomatis patients. C. trachomatis antibodies are associated with enhanced risk of developing squamous cell carcinomas, but not for cervical adenocarcinoma.
Endocervical glandular cells are targeted by C. trachomatis. With increasing age, the endocervical epithelium undergoes metaplasia, and the metaplastic cells are more prone to be infected C. trachomatis. Chlamydia infected cells are more likely to have DNA damage compared to cells not infected with chlamydia. This kind of DNA damage is not necessarily corrected by the cell subsequently increasing the chances of genetic mutation. Studies have revealed that the risk of metastatic disease is higher than localized disease among such patients. The researchers also found that three types of chlamydia (serotypes G, I, and D) are associated with development of cervical cancer.
Studies have revealed that women with diets low in fruits and vegetables are more prone to develop cervical cancer. Obese women have higher probability to develop adenocarcinoma of the cervix.
Studies have also revealed that diet low in folate, retinol and vitamin E also increase the chance of developing squamous cell carcinoma of cervix. Vitamins C and B12, alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin and cryptoxanthin lower the risk of developing cervical cancer.
High blood homocysteine has been associated with increased risk of cervical cancer. But, current evidence for an association between diet and cervical carcinogenesis is not yet substantial. Large cohort studies are required to find out exact association between diet and cervical carcinogenesis.
Birth control pills
Birth control pills especially their long-term use of birth control pills increases chances of developing malignant changes in cervix.
Research suggests that the risk increased after long term use of “the pill,” but the risk decreases substantially again after woman stops taking it. Doctors should discuss pros and cons of birth control pills before prescribing it to their patients. Research revealed that women who took birth control pill for more than 5 years were two times more prone to develop cervical cancer. One more study revealed 10% enhanced risk for less than 5 years of use of birth pills, a 60% increased risk with 5–9 years of use, and 2 times more risk with 10 or more years of use of contraceptive pills.
Changing the method of contraception in women with more than one risk factors is always the best option to avoid menace of cancer. They should be advised a yearly pap smear test to rule out any malignant change in the mucosa.
Having multiple pregnancies
Women who have had multiple pregnancies have an enhanced risk of cervical cancer. Research is yet to establish substantial cause for this association. It was seen that women with 3 or more full term pregnancies are more prone to cervical cancer. Doctors and researchers believe that multiple pregnancies result in decreased function of immune system making the body vulnerable to infections and genetic mutations leading to development of cancer.
Engaging in early sexual contact
Early age at first sexual intercourse can also make women more vulnerable to develop cervical cancer. Early age at first sexual intercourse (AFSI) makes women susceptible to high-risk human papillomavirus (HPV) infections and other sexually transmitted diseases. HPV and several sexually transmitted infections like Chlamydia take part in carcinogenesis of cervix. Sexual behavior of an adolescent women can also determine the extent of risk of cervical cancer. Women who frequently engage in unprotected sex, have multiple sexual partners are more prone to develop cervical cancer. It has also been revealed that the enhanced risk of HPV in young women is because of a biological predisposition of the juvenile cervix during puberty that may be more vulnerable to HPV infections. The significance of HPV-vaccination is further increased in young adolescent females before their first sexual intercourse as it can go a long way in decreasing the incidence of cervical cancer. Doctors should provide sexual education and encourage family planning to further reduce the risk of cervical cancer among young females.
Young age at the time of first full-term pregnancy
It has been proven by research that pregnant women younger than 17 years are almost 2 times more prone to develop cervical cancer later in life than women who got pregnant until they were 25 years or older. Adolescent cervix is more vulnerable to HPV infection.
Poor women are at high risk for invasive cervical carcinoma. This may be attributed to the fact that they cannot afford regular screening methods like pap smear. Pap smear has to be followed by colposcopy to further evaluate the abnormal cellular changes in the cervical mucosa. Premalignant changes, if left untreated can develop into full-blown invasive cervical carcinoma.
Research published in British Journal of Cancer revealed that poorer women have an enhanced risk of developing cervical cancer because they were found to engage in sex four years earlier than more affluent women.
DES is a hormone drug that had been used to prevent miscarriages and other complications of pregnancy. Research has proven that the daughters of women who took this drug in pregnancy have a slightly higher risk of developing cervical cancer. The daughters of women who used DES in their pregnancy are about 40 times more vulnerable to develop clear cell adenocarcinoma of the cervix than women who did not use DES.
However, clear cell adenocarcinoma is not very common. In fact, approximately 1 in 1,000 DES daughters suffers from this type of cancer. Research has shown that the risk of developing this type of cancer increases as women age into their 40s.
DES daughters are more prone to develop abnormal cells in the cervix and the vagina that are premalignant. These premalignant changes include dysplasia, cervical intraepithelial neoplasia, and squamous intraepithelial lesions. They may develop into invasive carcinoma if left untreated. It has been advised that DES daughters should have regular screening tests. A yearly Pap test and pelvic examination to check for abnormal cells is often recommended by the doctors. Nowadays, DES is obsolete and not used by the obstetricians in order to avoid the risk of developing cervical and vaginal carcinomas.
Multiple sexual partners
Research has revealed that there is enhanced risk of both malignant and non-malignant cervical diseases in individuals with multiple sexual partners compared to individuals in monogamous relationship. There are several potential theories that can explain the association. The vulnerability to cervical cancer enhances with the number of sexual partners because of more chance of getting HPV and other sexually transmitted diseases. Studies have also revealed that risk enhances with increase in number of sexual partners. Research is still insignificant to prove multiple sexual partner as an independent risk factor for cervical cancer.
Sexually transmitted diseases
Sexually transmitted diseases may not cause cervical cancer directly but they surely enhance the risk of developing cancer. Chlamydia and Gonorrhea are both documented to play their role in carcinogenesis of cervix. In one study, HSV-2 was found in 50% of women suffering from cervical cancer. Researchers at the ‘International Agency for Research on Cancer’ have revealed that women infected with both HPV and HSV-2 were 2x are more vulnerable to develop cervical cancer. 2,400 women living in seven countries in Asia, Europe, and Latin America took part in this study. This study also revealed that Asian women are most vulnerable to develop cancer of cervix. A yearly pap screening test is advised to all women under 25 years of age. The association of sexually transmitted infections with cervical cancer can also be explained with their possible synergistic action in cervical carcinogenesis. Sexually transmitted infection can cause cervicitis that can hinder the clearance of HPV strains. These persistent HPV strains ( HPV 16, 18, 33) eventually cause cervical cancer.
Cervical cancer can occur in a person with family history. If your mother or sister suffered from cervical cancer, you are 2 to 3 times more vulnerable to develop cervical malignancy than if no one in the family had it. This can be because women with family history have less ability to fight off HPV than other women. Several genetic mutations run in families that make women more prone to develop cervical cancer. It is highly recommended for such women to get vaccinated and visit healthcare center for pap test and pelvic examination once a year.
Each year, more than 13,000 women in the United States develop cervical cancer. Cervix is predisposed to malignant changes due high cell turnover in the transformation zone. Various causes are identified after rigorous research over several years. PV infection, multiple pregnancy, multiple sex partners, sexual intercourse at an early age, pregnancy at an early age, Chlamydia infection and weakened immune system are major causes of cervical cancer. Although these risk factors increase the probability of developing cervical cancer, many women exposed so these causes do not develop cervical cancer in their life. Screening methods like pap smear and pelvic examination are recommended for women who are more prone to develop cervical cancer. Routine screening has dramatically decreased the incidence of cervical cancer.