Causes of cervical cancer: Understanding leads to Effective Prevention

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Cervical cancer is an excessive growth of pathologically changed cells in the lower part of the uterus (cervix of the uterus). It is the second most common type of cancer in women. In most cases precancerous or cancerous changes arise in the transformation zone of the cervix, especially when we are talking about common causes of cervical cancer. Transformation zone is the area between two different types of epithelium (covering of all inner organs) – the first one is located inside the cervix, the second one is located outside the cervix. Cells of the transformation zone are very active, as they constantly renew. During this permanent process certain amount of cells lose normal qualities and becomes atypical.

Normally atypical cells are detected by protective mechanisms and eliminated immediately. In case of additional harmful factors presence, the number of atypical cells increases dramatically, defense mechanisms fail to cope with them and this eventually causes cervical cancer.The most dangerous factor, which may lead to cervical cancer development, is infection with high-risk types of the human papillomavirus (HPV). We will talk about high-risk types of HPV that cause cervical cancer and other risk factors in this article.

Content

1. Causes, risks and risk factors
2. How risk factors lead to cervical cancer development
3. Main risk factor of cervical cancer development: HPV
4. Additional possible causes of cervical cancer development
5. From causes of cervical cancer to preventing the disease
6. From causes of cervical cancer to screening tests
7. Choosing an appropriate clinic for cervical cancer screening and prevention

Causes, risks and risk factors

Regarding the causes of any condition, we can see two variants of interdependence:

• Direct causes. For example, if you are allergic to dogs and spend all day long outdoors playing with neighbor`s pet, you will start sneezing and perhaps have an adverse reaction. In this situation we have certain factor (contact with a dog) that leads to certain subsequence (allergic reaction).
• Risk factors. For example, if you go for a walk without an umbrella and the rain starts, you will get soaked and may catch cold. On the other hand, you may stay healthy; it depends only on your immunity. So, in this situation we don`t have any direct connection. Bad weather may provoke the disease, and may not; this is only a possibility.

In cervical cancer we can define only risk factors, not the direct understanding of how cervical cancer is caused. Risk factor is anything that increases chance of getting the illness. Nevertheless, you should clearly understand that having one or more risk factors is not equal to 100 % probability of developing the condition. Beyond all doubt, women without risk factors become ill rarely. On the other hand, women with combination of few unfavorable conditions may remain healthy their whole life. Moreover, even when the diagnosis of cervical cancer is confirmed, we will never determine certain risk factors, which have played the most essential role.

All cervical cancer risk factors may be divided into two groups:

1. Modifiable risk factors. We can influence cervical cancer causes from this group. For example, we can change sexual behaviour, treat infections, avoid smoking.
2. Non modifiable risk factors. Cervical cancer causes from this group can`t be changed. For example, we can`t change genetic factors, age or certain concomitant diseases.

Preventive measures are mainly focused at modifiable risk factors. Non modifiable risk factors should be taken into consideration when providing preventive check-ups. Women with one or more risk factors should visit the doctor for a regular examination and follow all doctor`s recommendations.

How risk factors lead to cervical cancer development

As mentioned before, cervix of the uterus consists of basically two different parts. Lining of the inner part of the cervix is similar to the uterus one, while lining of the outer part of the cervix is similar to the vagina one. Border zone between these two parts is called transformation zone; all causes of cervical cancer mainly apply here. Cells of the transformation zone, as all epithelial lining cells, have short duration of life – they are substituted with new cells approximately in 10-14 days. In order to restore dying components in such short period of time, cells need to divide and give origin to new generations. Key point of cells division is doubling DNA – genetic material, which is the basis of all subsequent processes. Active metabolism and high speed of reproduction may cause abnormalities in DNA synthesis.

In certain circumstances cells with broken DNA acquire new features:

• Don`t die in the ordinary period of time
• Divide intensively and form unstructured tissue mass

Possible causes of cervical cancer are usually connected with damage in specific groups of the DNA areas:

• Oncogenes. These genes promote endless dividing of cells and may prevent them from becoming mature.
• Tumor suppressor genes. These genes ensure normal duration of existence for actively dividing cells. Damage of tumor suppressor genes compensatory activates oncogenes.

Cervical cancer risk factors directly or indirectly increase activity of oncogenes or lower activity of tumor suppressor genes, which finally leads to the same result – development of cancer. For example, high-risk types of HPV contain harmful for cervical cells genetic material. In addition to this direct influence on the DNA, HPV types that cause cervical cancer produce proteins E6 and E7. These proteins depress tumor suppressor genes, which allow HPV to multiply faster in the body. Other risk factors mainly have indirect effect, as they create more favorable conditions for high-risk types of HPV.

 

 

Main risk factor of cervical cancer development: HPV

The most essential leading cause of cervical cancer development is persistence of the human papillomavirus (HPV).

HPV – is the extremely widespread in the modern world, sexually transmitted viral infection of the reproductive tract. HPV is constantly mutating (changing genetic material) to be more viable inside the human body.

The virus is able to affect all parts of cervix:

• When HPV types that cause cervical cancer damage the outer part of the cervix there is risk of squamous cell carcinoma development; this happens in 80 % of cervical cancer cases
• When HPV types that cause cervical cancer damage the inner part of the cervix there is risk of adenocarcinoma (neoplasm from glandular cells) development; this is a less frequent type of oncological process

Actually, HPV is not a single virus, but a vast group of viruses. The total number of HPV strains comes up to 100 types; all of them affect skin and mucous membranes of the human. Nearly 40 of all HPV strains affect the genital area of men and women (including skin, vagina, vulva, penis and scrotum). Among them, 13 types are proven to create high risk of developing different types of cancer, while other ones are relatively safe. When we are talking about cervical cancer, HPV type 16 and HPV type 18 cause more than 70 % of cervical cancer and precancerous cervical lesions.

HPV types that cause cervical cancer are transmitted from human to human via sexual intercourse. Infection does not even require vaginal sexual contact – skin-to-skin genital contact is  enough. Also HPV may be successfully transmitted via oral sex or sex toys, from man to man, or from woman to woman. As a matter of fact, up to 80 % of people are infected with HPV once they become sexually active. Contact with the virus has no obvious symptoms, you may not even know about this. If HPV is eliminated from the human body naturally, reinfection is still possible, as there is no strong immunity to this pathogenic agent.

When a person is infected with HPV of any type, natural defense mechanisms are activated. Usually main protective force is the production of antibodies against the virus that causes cervical cancer or direct action of protective cells – leukocytes. In most healthy people HPV infection will be completely eliminated in approximately 2 months without any medical intervention.  To be more precise, 90 % of infected people will eventually be  cured within 2 years. In other cases, especially in other risk factor presence, HPV can remain viable and persist in the body.

With the lapse of time, persistence of certain HPV types may cause cervical pre-cancer changes and cervical cancer. Or, as another possible variant, the virus may remain inactive (“dormant”) for a while. In this state HPV is invisible to all defense mechanisms. The virus that causes cervical cancer renews its activity later, in more favorable conditions. In this dormant state the virus is still dangerous for a person`s sexual partners. For example, it may cause penile cancer. An infected woman does not face any symptoms. Actually, obvious signs may arise only in cervical cancer development, and even then women may attribute manifestations to infections, menstrual cycle disturbances, and urinary tract problems. HPV does not always cause cervical cancer. We should remember that cervical cancer is not the only consequence of HPV infection.

Other less dangerous manifestations of HPV infection include the following:

• Genital papillomas (or warts), usually caused by HPV type 6 and HPV type 11. We don`t talk about oncological alertness in this case, genital warts do not cause cervical cancer. Nevertheless, a person with genital warts may be additionally infected with more dangerous HPV types.
• Respiratory papillomas. They arise along all respiratory tract and cause physical discomfort while breathing .

In general, being infected with HPV is the most serious cervical cancer risk factor, but at the same time this is the main potentially avoidable condition.

 

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Additional possible causes of cervical cancer development

Additional conditions, which influence the possibility of cervical cancer development, mainly include factors that promote HPV persistence. Some of these factors are modifiable, so we can change them and minimize the risk; others are non modifiable, so we just take them into consideration and pay additional attention to preventive measures.

So, what can cause cervical cancer besides HPV infection?

• The first factor is early beginning of sexual life (by “early” we mean “before 18 years old”). As we have already mentioned before, start of sexual activity is almost equal to infection with HPV, as this virus is really ubiquitous. Longer the period of exposing to the virus is, higher is the chance of cervical cancer development.
• Number of sexual partners. Women with one regular sexual partner have fewer chances to develop the disease than women with numerous sexual partners. It is connected with constant HPV reinfection and exposing to diverse types of HPV.
• Presence of other sexually transmitted diseases (STD). Diagnosing genital herpes, syphilis or chlamydia infection increases the possibility of cervical cancer development, as these infections change the normal state of the cervix. Cervical cancer caused by STD is treated by the team of oncologist, gynecologist and infectious diseases specialist. Asymptomatic course of concomitant infections is dangerous, as well.
• Immune system suppression. Impaired function of the immune system leads to poor elimination of the virus that causes cervical cancer. In addition, the period of time before cervical cancer development is reduced. It takes about 15-20 years to develop cervical cancer in women with normal immunity; in women with immune system suppression 5 years is enough. The most common causes of immunosuppression are HIV-infection, long-term steroid intake, treatment for other types of cancer or treatment after organ transplantation, depression, and continuous mental stress.
• Smoking or using other tobacco products. Contact with tobacco is strongly associated with squamous cell cervical cancer. You may be surprised with this fact and wonder, how does smoking cause cervical cancer. Nicotine and additional substances from cigarettes have a direct influence on cervix of the uterus and suppress the immune system in addition. Breathing second-hand smoke is as harmful, as smoking personally. Risk is not the same for all smokers and depends on the number of cigarettes per day and number of years a woman smokes. Past experience of tobacco using is not relevant, as risks return to normal once a person quits.
• Having 3 or more full-term pregnancies. In addition, if a woman had her first pregnancy being under 17 years old, the risk doubles as compared to pregnancy after the age of 25. Possible causes of cervical cancer in this case are the mechanical influence on cervix of the uterus during pregnancy and delivery, and concomitant immunosuppression. First pregnancy before 17 years old means early beginning of sexual life, which is the risk factor itself.
• Using birth control pills during 5 years and more. Drugs of this group change hormone levels and usual state of reproductive system. This makes cervix of the uterus more vulnerable to viral infections. Nevertheless, risk reduces within 2 years after the drug withdrawal.
• Family history of cervical cancer. Diagnosis of cervical cancer in first-degree relatives is really worth attention when we talk about causes for cervical cancer. This may be connected both with genetic factors and habits of life, so risk may be somewhat modified. Another risk factor is having cancer in the past, especially cancer of vagina, vulva, kidneys, and urinary tract. Increased risk of cervical cancer development is explained by both oncological alertness and influence of previous treatment.
• Exposure to diethylstilbestrol (DES). DES is a drug, estrogen; it was widely prescribed to pregnant women in the 1940-s to avoid miscarriages. Children, born from those women, are highly likely to develop cervical cancer. DES was forbidden for medical use and removed from the market in the 1970-s, when this side effect showed itself. You may ask your mother about taking this drug while being pregnant.
• Social and economic factors. Women, who are not able to visit a doctor regularly and go through annual examination, are more likely to have cervical cancer. This is another evidence of preventive examinations value. The same time cervical cancer causes and prevention are closely associated with availability of the medical services.
• Overweight, low physical activity and diet poor of fruits and vegetables. These are totally modified risk factors, which may be avoided in  the general scope of healthy lifestyle.
• Age. Women from 35 to 55 years old are at the maximum risk of the cervical cancer development. In this point we mainly talk about general risk, based on the combination of all previous factors.

From causes of cervical cancer to preventing the disease

There is no 100 % proven way to completely avoid cervical cancer, but you can make your oncological risk significantly lower.

Following recommendations were elaborated on the basis of most important cervical cancer risk factors analysis:

• Education, improving sexual literacy
• Delayed start of sexual activity
• Using condoms, avoiding sexual contacts with obviously infected partners
• Avoiding smoking and using other tobacco products
• Personalized choice of contraception method, as some variants of birth control can cause cervical cancer
• Undergoing an annual examination once per year starting from 21 years old
• For men – performing circumcision

One more effective way of cervical cancer prophylaxis is vaccination. Nowadays vaccination against high-risk HPV types is performed in more than 65 countries. Currently available vaccines are Gardasil, Gardasil 9 and Cervarix. Cervarix and Gardasil fight causes of cervical cancer – HPV type 16 and HPV type 18, and show cross-protection against other less pathogenic HPV types.

Few peculiarities of vaccination against HPV:

• It is better to apply the vaccine before the first sexual activity and contact with HPV. Both girls and boys can be vaccinated. Optimal variant of vaccinating children is performed in 3 procedures over  an 8-month period.
• Vaccines can`t treat HPV-infection or HPV-associated diseases (like cancer). Sole aim of this manipulation is the prophylaxis. HPV vaccine protects from causes of cervical cancer.
• Although risk of developing cancer becomes significantly lower, vaccination doesn`t eliminate regular screening tests.

From causes of cervical cancer to screening tests

As we go through the list of cervical cancer risk factors, it becomes obvious that each and every woman of certain age is subjected to the risk of cervical cancer development. Beyond all doubt, the first priority is prevention of the disease. Indeed, we are able to avoid most of the modified risk factors. Unfortunately, we can`t influence such non modified risk factors as genetics or presence of oncological diseases in the anamnesis. That is why, it is really important to perform annual preventive examination in women from high-risk groups. Preventive examination may include different screening tests; it depends on the level of medical service in the country.

Basic examination regardless presence of cervical cancer causes consists of the following investigations:

• Colposcopy with acetic acid. During this manipulation a doctor directly examines cervix of the uterus with the help of special magnifying glass – colposcope. Application of the acetic acid makes the procedure more informative.
• Pap test (or Pap smear) and liquid-based cytology. During this manipulation a doctor takes some cells from the cervix and investigates them under the microscope. The main aim of performing this test is to reveal precancerous changes – cervical intraepithelial neoplasia (CIN), which may advance to cancer in the course of time.
• HPV test. In general this investigation is somewhat similar to Pap test, but it is pointed at revealing HPV genetic material (DNA) in the cells from cervix.During this test we are looking for HPV types that cause cervical cancer.

Screening tests in different risk groups have certain peculiarities, but their common aim is revealing the disease at an early stage.

 

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Choosing an appropriate clinic for cervical cancer screening and prevention

When you think about avoiding cervical cancer causes and prevention, several factors should be considered as the most significant ones:

• Having an appointment with qualified doctor, examination, and competent estimation of all risk factors.
• Performing screening tests with the help of modern diagnostic equipment in combination with excellent skills of healthcare providers, as these tests are somewhat subjective.
• Good quality laboratory investigation of vaginal smears.
• Availability of vaccines against the virus causing cervical cancer and competent estimation of indications for vaccination.

Investigation of related official information, world statistics and patients` reviews will lead you to the option of examination and, if necessary, preventive treatment in Germany. German medicine guarantees good quality of preventive vaccination, effective modification of possible causes of cervical cancer and reliable screening tests. Incidence of cervical cancer in Germany is lower than 35 cases per million women a year, and even in these cases the disease is revealed at an early stage, when the curing potential is relatively high.

When planning check-up or treatment for cervical cancer caused by HPV in Germany, services of Booking Health company will be really helpful for you.  The aim of our work is to assist foreign patients in receiving medical help, and we are officially authorized by clinics to provide such services.

Booking Health company will give you a helping hand and:

• Recommend the best doctor and clinic for your case
• Book an appointment at a convenient date
• Organize comprehensive medical program
• Provide you with transfer, interpreter and medical coordinator
• Provide you with medical insurance
• Prepare all the medical reports and further recommendations in your native language for you
• Help you in further communication with your treating physician, if necessary

To start planning your medical trip, please, leave a request on the Booking Health website. You will be contacted by our informative case manager the same day to discuss all the possible options. We will be glad to assist you in combating the main causes of cervical cancer and receiving timely prophylaxis.

 

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Authors:

The article was edited by medical experts, board certified doctors Dr. Vadim Zhiliuk, Dr. Sergey Pashchenko. For the treatment of the conditions referred to in the article, you must consult a doctor; the information in the article is not intended for self-medication!

 

Sources:

National Center for Biotechnology

Cancer Research Institute

National Cancer Institute

 

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