Cervical (or cervix) cancer: here are the symptoms and treatments

By Cristiano Antonino On May 10, 2023

Cervical (or cervix) cancer develops in the lower part of the uterus, the organ of the female apparatus where the embryo is received and develops during pregnancy

The uterus is shaped like an inverted funnel and consists of two main parts: the upper part is called the body of the uterus, while the lower end is called the neck or cervix.

The cervix is in direct connection with the vagina and can be divided into two parts called the endocervix (the one closest to the body of the uterus) and the ectocervix or exocervix (the one closest to the vagina).

The cells lining these two areas of the cervix are not the same: squamous cells are found in the ectocervix and glandular cells in the endocervix.

The two cell types meet in the so-called transition zone.

Most cervical cancers originate precisely from cells found in this ‘border’ zone.

What is cervical (or cervix) cancer?

Cervical cancer develops in the lower part of the uterus, the organ of the female apparatus where the embryo is received and develops during pregnancy.

The uterus is shaped like an inverted funnel and consists of two main parts: the upper part is called the body of the uterus, while the lower end is called the neck or cervix.

The cells lining these two areas of the cervix are not the same: squamous cells are found in the ectocervix and glandular cells in the endocervix.

The two cell types meet in the so-called transition zone.

Most cancers of the cervix originate precisely from cells found in this ‘border’ zone.

How widespread it is

For a long time, cervical cancer was the most frequent form of cancer for women globally, but in recent years the situation has changed dramatically.

According to the report ‘Global Cancer Statistics 2020’, produced jointly by the American Cancer Society (ACS) and the International Agency for Research on Cancer (IARC), cervical cancer ranks fourth among the most common cancers in women and accounts for 6.5 per cent of all cancers diagnosed in women.

The same report also indicates that this is the most common cancer especially in 23 countries, many of them low- and middle-income and located on the African continent.

In the western world, the number of cases and the number of deaths continue to fall, thanks mainly to the Pap-test and the subsequent introduction of the test for Papillomavirus (HPV) DNA, two very effective tests for early diagnosis.

Every year in Italy there are around 2,400 new cases, 1.3 per cent of all cancers diagnosed in women, according to the data in the report ‘The numbers of cancer in Italy, 2020’ by, among others, the Italian Association of Cancer Registries (AIRTUM) and the Italian Association of Medical Oncology (AIOM).

In our country, the 5-year survival rate from diagnosis of cervical cancer patients is 68 per cent and every year around 500 women die from the disease (ISTAT data 2017).

These figures are set to change further over time.

Today, in fact, we have very effective prevention, diagnosis and treatment tools against this cancer, which prompted the World Health Organisation (WHO) to launch on 17 November 2020 the Global Strategy to accelerate the elimination of cervical cancer as a public health problem, a goal to be achieved within a few decades.

Cervical (cervix) cancer, who is at risk?

One of the main risk factors for cervical cancer is infection with the human papilloma virus (HPV), which is mainly transmitted sexually.

This is why certain measures that limit the chances of infection (condom use and especially vaccination) protect against this type of cancer, although they are not 100 per cent effective.

The condom, for example, does not completely protect against infection, since the virus can also be transmitted through contact with regions of the skin not covered by the condom.

An early start to sexual activity and multiple sexual partners can increase the risk of infection, as can an immune deficiency, which can be linked to various causes (e.g. an HIV infection, the AIDS virus, or a previous organ transplant).

However, it must be remembered that not all HPV infections equally increase the risk of developing cervical cancer.

Most women who come into contact with the virus are in fact able to eliminate the infection thanks to their immune system without subsequent health consequences.

Finally, it has now been established that only a few of the more than 100 types of HPV are dangerous from an oncological point of view, while most remain silent or merely give rise to small benign tumours called papillomas and also known as genital warts.

Other factors that may increase the risk of cervical cancer are cigarette smoking, the presence of close relatives with this cancer in the family (although no genes responsible for any familial relationship have been identified), a diet low in fruit and vegetables, obesity and, according to some studies, even chlamydia infections.

Types

Cervical cancers are classified according to the cells from which they originate and are mainly of two types: squamous cell carcinoma (about 80 per cent of cervical cancers) and adenocarcinoma (about 15 per cent).

We speak of squamous cell carcinoma when the cancer arises from the cells covering the surface of the exocervix and of adenocarcinoma when the cancer starts from the glandular cells of the endocervix.

Finally, although less common (3-5 per cent of cervical cancers), there are cervical cancers that have a mixed origin and are therefore termed adenosquamous carcinomas.

Symptoms

The early stages of cervical cancer are usually asymptomatic and any symptoms may be related to other non-cancerous conditions.

Alarm bells that may raise suspicion of cervical cancer include, for example, abnormal bleeding (after sexual intercourse, between menstrual cycles or during menopause), vaginal discharge without blood or pain during sexual intercourse.

Prevention

In most cases, the cells that can lead to cervical cancer do not immediately give rise to actual cancer, but initially generate what doctors call precancerous lesions.

These lesions are called CIN (cervical intraepithelial neoplasia), SIL (squamous intraepithelial lesion) or dysplasia and may progress slowly over years to the cancerous form.

In reality, not all precancerous lesions give rise to cancer: in many cases they regress spontaneously without any treatment.

However, there is no doubt that preventing the formation of such lesions, or diagnosing and treating them early, can drastically reduce and almost eliminate the occurrence of cervical cancer in the population.

Limiting the number of sexual partners and trying to avoid relations with people at risk remain two possible prevention strategies, but undoubtedly the winning approach to diagnosing the pre-cancerous stage is based on regular gynaecological check-ups.

During the examination, the gynaecologist can perform the Pap test, a quick and painless test that can identify pre-cancerous or cancerous lesions in their early stages and is part of the national cancer screening plan.

The gynaecologist can also perform, as is now recommended, the HPV-test, a test that directly detects the presence of HPV DNA.

From the age of 25 up to the age of 64, all women are offered one of these two screening tests free of charge, which must be repeated regularly every three years (Pap-test) or five years (HPV-test) in the event of a negative result, or more frequently in special cases.

For several years now, there has also been another weapon against the Papilloma virus: a vaccine capable of warding off the two most frequent types of HPV responsible for most cervical cancers (HPV16 and HPV18) and also other less frequent ones.

In Italy, the vaccine is now recommended and offered free of charge to girls and boys in their twelfth year of age.

It is also important to remember that vaccination can guarantee prevention of all HPV-related cancers, such as those of the vagina, vulva, anus, head and neck.

Diagnosis of cervical (cervix) cancer

Cervical cancer can be diagnosed at a very early or even precancerous stage if regular screening with a Pap-test or HPV-test is performed.

Based on the test results, the doctor will then be able to determine how aggressive a possible pre-cancerous abnormality is likely to be and decide on a more effective intervention strategy.

If abnormalities are found, the doctor may prescribe further tests, such as colposcopy, a test that takes only a few minutes, is painless and is performed by the gynaecologist in the outpatient clinic.

Smaller lesions can also be removed during colposcopy to eliminate the risk of them developing into cancer.

If there is a diagnosis of cervical cancer, tests such as computed tomography (CT), magnetic resonance imaging or positron emission tomography (PET) may be prescribed to determine the extent of the tumour more precisely.

Evolution

Cervical cancer can be classified into four stages (I to IV) depending on how far it has spread in the body.

As with other types of cancer, the lower the stage, the less widespread the disease and the greater the likelihood of cure.

How to treat

The choice of treatment depends primarily on the stage of the disease at the time of diagnosis, but is also based on other criteria such as the person’s general health, age and needs.

In addition, a combination of two or more treatments is often used to achieve maximum effectiveness.

Surgery is one of the possible choices and the type of intervention varies depending on the spread of the disease.

In the earliest stages, when the tumour is in a pre-invasive phase, cryosurgery or laser surgery may be used, which respectively use cold or a laser beam to freeze or burn the diseased cells.

When the tumour is somewhat more diffuse, but still confined to a limited area of the cervix, the choice may fall to so-called conization, an operation in which a cone of tissue at the lesion is removed without compromising the function of the organ and the possibility of having children.

If, on the other hand, the tumour is more extensive, we move on to hysterectomy, an operation in which the uterus, lymph nodes, tubes and ovaries are removed.

Radiotherapy, which targets tumour cells with radiation, is a valid treatment for locally advanced disease, usually in combination with chemotherapy (radiochemotherapy).

In addition to traditional radiotherapy, in which the radiation source is external, brachytherapy, i.e. the insertion of small radiation-emitting ova into the uterus, is also used.

Both external therapy and brachytherapy keep the reproductive system intact and do not, in many cases, affect the ability to have a normal sex life.

A third option for the treatment of cervical cancer (reserved, however, for advanced or invasive forms) is chemotherapy: several drugs against the tumour are administered intravenously, often in combination, including cisplatin, paclitaxel, and the anti-angiogenic bevacizumab.

Immunotherapy with drugs such as pembrolizumab, atezolizumab, nivolumab, ipilimumab-nivolumab, is being investigated for the treatment of cervical cancer and is considered a promising option in this disease, which in more than 90 per cent of cases expresses the PD-L1 molecule, the target of some of the immunotherapeutic drugs available today.

In the US, pembrolizumab has already been approved by regulators (Food and Drug Administration; FDA) for the treatment of PDL-1 positive advanced/metastatic cervical cancer.

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