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Cervical cancer

2

Cervical cancer is one of the malignant cancers which in the early stages are completely asymptomatic or whose early symptoms are minor and non-specific. Therefore, women who suffer from more distinctive symptoms are usually diagnosed with advanced cervical cancer.

Most often, those symptoms include one or more of the following:
- contact bleeding (bleeding during sexual intercourse or a pelvic exam),
- bleeding between regular menstrual periods,
- menstrual periods longer and heavier than usual,
- abnormal (heavy) vaginal discharge,
- pain during intercourse,
- abdominal pain.

If cervical cancer infiltrates the closest organs or metastasizes to remote organs, following symptoms might occur:
- pelvic pain
- urinary incontinence (loss of bladder control),
- urinary retention, hydronephrosis,
- flatulence, alternating diarrhoea and constipation,
- severe pain in the pelvic bone and/or other bones (e.g. the thigh bone)
- persistent, therapy-resistant cough,
- neurological symptoms,
- other.

The final diagnosis of cervical cancer is usually made by an experienced gynaecologist or a gynaecologic oncologist after administering necessary tests, such as:
1. pelvic examination;
2. the Papanicolaou test (known commonly as Pap test or Pap smear);
3. colposcopic examination (colposcopy), during which biopsies might be taken for further histophtological examination;
4. histopathology of the biopsy material, with full report from the pathomorphologist.
(See: What Tests Will the Doctor Order?)

Remember:
If you notice any lasting symptoms in relation to your reproductive organs, you should see your gynaecologist.

Cervical cancer is a malignant cancer that originates in the female reproductive organs, more specifically, in the conical part of the uterus (cervix) that connects the upper part of the uterus (corpus uteri) with the vagina.

The main, confirmed cause of cervical cancer is human papillomavirus (HPV) infection, which infiltrates epithelial cells of the cervix, and then damages and “reprograms” them – they start to divide uncontrollably and, as a result, form a tumour. The tumour can infiltrate and damage neighbouring tissue as well as metastasize – cancer cells “break away” from the primary tumour and, through blood or lymph vessels, travel to remote sites, “settling” there and forming new tumours. This way, a cancer originating in the epithelium of the cervix can damage, e.g., lung, liver, or bone tissue, which can cause the body to malfunction and ultimately lead to death of the patient.
Cervical cancer is the third most common cancer in women and the third most common cause of death from cancer among them.

The estimated number of women with cervical cancer worldwide is 1.4 million. Every year there are approx. 500 000 new cases, and approx. 300 000 women die of cervical cancer.
In Poland, there are over 3000 new cases per year, and over 1700 women die of this type of cancer annually. It is one of the highest mortality rates in Europe.

Cervical cancer is most common in women between 35 and 59. It attacks quietly and slowly. On average, it develops for 14 years. For years, the development of cervical cancer is virtually asymptomatic. The appearance of distinctive symptoms usually means that the cancer is in an advanced stage, therefore difficult or impossible to cure.

HPV infection is usually contracted through sexual intercourse; the infection may be almost completely asymptomatic. Every sexually active woman at least once in her life comes into contact with HPV; however, the infection develops into a disease only in up to 20% of women. Most infections are killed by the immunological system and don’t cause cervical cancer. Some of them, however, develop into a chronic condition lasting years. An important consideration is the type of HPV contracted – types 16 and 18 (called the oncogenic types) are responsible for two thirds of total cervical cancer cases.

Men are usually asymptomatic carriers of the virus and it is they who infect their sexual partners. Larger number of sexual partners increases chances of the infection but cervical cancer is a threat to every sexually active woman – even one who has sexual contact with only one partner.
Even very young women who have just started to be sexually active can be infected. The virus can then insidiously develop for a long time without causing any distressing symptoms, which after several years – usually when the woman is at the age when she is most active in her professional and family life – results in cervical cancer.

Apart from HPV infection, other confirmed factors increasing the risk of cervical cancer include: early sexual initiation, large number of sexual partners, frequent pregnancies and childbearing, and smoking.

Cervical cancer is one of the few malignant cancers in which screening tests have been proven to significantly lower incidence and mortality rates.

Currently, Pap test is the standard screening test used in cervical cancer preventive care around the world. The test allows finding precancerous changes (cervical interstitial neoplasia – CIN) and cancer in the early stages (e.g., in the “in situ” stage, when the cancer is not yet invasive). At that stage, surgical treatment normally results in full recovery of the patient, without maiming her; often, it doesn’t even affect her fertility or the ability to gain full satisfaction from sexual intercourse.

In Poland, a routine Pap test is recommended every 3 years for women aged 25 - 59. The exception are women with pre-existing risk factors: those infected with HIV, taking immunosuppressants, or infected with a high-risk type of HPV. Those women should do a Pap test every 12 months. Every gynaecologist who signed an agreement with the NFZ (the National Health Service) will do the test free of charge.

Since 2006, a vaccination against HPV, the virus responsible for cervical cancer, is also available. Currently, the American Advisory Committee on Immunization Practices (ACIP) recommends the vaccination to all females aged 11 – 12 or 13 – 26, if not vaccinated before. In other countries, the recommended age group for HPV vaccination is somewhere between 9 and 18 years old; most often it is 11 – 13 years old, that is, before sexual initiation. HPV vaccines have been proven to be highly effective in preventing diseases related to HPV infections, including the oncogenic types. The efficiency of the vaccine in preventing cervical cancer is rated very high: the risk of squamous cell carcinoma (the most common type of cervical cancer; approx. 85% of total cases) is reduced by 75% and the risk of adenocarcinoma (10% of total cervical cancer cases) – by 96%.
It is estimated that the currently available vaccines prevent 70-80% of cancers caused by HPV.

Remember:
Cervical cancer can be successfully prevented through:
1. primary preventive care – vaccinations against human papillomavirus (HPV);
2. secondary preventive care – regular Pap tests.

Currently, the diagnostic standard, that is, the battery of medical tests most effective in diagnosing and treating cervical cancer, consists of the following:

To find and diagnose cervical cancer:
1. pelvic examination – sometimes, lesions suspected of malignancy are visible during a standard pelvic exam. Unfortunately, such lesions are usually already advanced;
2. the Papanicolaou test (Pap test or Pap smear) – a very important screening test, whose sensitivity in detecting cervical cancer and precancerous changes (cervical dysplasia – i.e., an abnormal, “pathological” condition that can transform into malignant cancer) is between 77 and 98%.
Pap test is completely painless and very quick. It involves collecting a sample of cells from the os and canal of the cervix with a swab during a pelvic exam. Then, in a laboratory, the sample is inspected under a microscope to assess the state of epithelial and glandular (mucus-producing) cells of the cervix.
The results of the test are reported in terms of 5 cytology classes introduced by Papanicolaou. Classes I and II mean that the results are normal.
3. Colposcopic examination (colposcopy) – this test is used when the results of the Pap test are abnormal. However, a referral to colposcopy does not automatically mean that cancer is present! The vast majority of colposcopies do not result in this diagnosis.
Combined with Pap test, colposcopy increases the efficiency of confirming or ruling out cervical cancer almost to 100%. Therefore, it is an important follow-up to Pap test and a necessary step before starting treatment for either precancerous changes or a malignant cancer.
Colposcopy, similarly to Pap test, is a quick and painless procedure performed during a pelvic exam (however, a slight “burning” or “pinching” sensation is possible when a biopsy is taken for a histopathological examination).
4. histopathological examination – the biopsy of abnormal tissue taken during colposcopy is sent to a laboratory, where a pathomorphologist, after analysing the tissue, gives the final diagnosis: inflammatory changes, precancerous condition, or cervical cancer.
On the basis of this information, the gynaecologist makes a decision regarding further diagnostics and treatment.
If there is any suspicion that the cancer infiltrated the urinary bladder or rectum, the doctor will recommend cystoscopy and colonoscopy.

Before and during treatment
After cervical cancer diagnosis, the next necessary step is to determine the stage of the disease. Tests which help with that include:
- a full physical examination (including lymph nodes assessment),
- a chest X-ray,
- standard blood and urine tests,
- a transvaginal or abdominal ultrasound (not as common as the others).
If the cervical cancer is locally advanced (a big primary tumour or infiltration of the neighbouring lymph nodes) the battery of tests may involve also:
- CT or MRI scans of the pelvis and abdomen, or a PET scan (positron emission tomography),
- biopsy of suspicious lymph nodes,
- cystoscopy and colonoscopy (if infiltration of the bladder and rectus is suspected),
- other tests deemed appropriate in a given situation.
The results of the tests determine the selection of further treatment.
The tests used during treatment depend on the administered form of therapy (e.g., surgical treatment, chemotherapy, or radiotherapy used as a sole treatment or in combination).

After treatment
During the first 2 years after the end of active treatment for cervical cancer, the patient should visit her gynaecologist for a follow-up every 3 months. The visit will include:
- a complete gynaecological examination,
- a Pap test.
Other tests are used only when a local recurrence or a metastatic disease are suspected.
For the following 3 years, the follow-up visits should occur every 6 months, once a year after that.

The treatment for cervical cancer may include:
1. Surgery
2. Chemoradiotherapy
3. Radiotherapy
4. Chemotherapy

The first step in choosing and starting the right treatment is the right identification of the stage of the disease.

Staging of cervical cancer is based on the FIGO classification system, with stages graded I-IVB.
Stage I means that the cancer is limited only to the cervix.
Classification into sub-stages IA, IA1, IA2, IB, IB1, and IB2 depends mainly on the depth of the infiltration into cervical tissue and the size of the tumour (its diameter).
Stage II means that the cancer has grown beyond the cervix but has not yet invaded the walls of the pelvis. It could have spread to the vagina but only in its upper part (the upper 2/3).
Classification into sub-stages IIA, IIA1, IIA2, and IIB depends on the question whether the tumour is larger than 4 cm, and whether it has spread to the tissues next to the cervix (the parametria – groups of connective tissues acting as ligaments located around the uterus and behind the peritoneal cavity).
Stage III means that the cancer has spread to the walls of the pelvis or to the lower part of the vagina. Additionally, one of the kidneys might not be working, or a condition called hydronephrosis might occur. Either can happen when the tumour infiltrates or pinches a ureter and the urine cannot drain out of the kidney.
Classification into sub-stages IIIA and IIIB depends on which of these factors have occurred.
Stage IV means that the cancer has spread to other organs.
Sub-stage IVA means that the tumour has invaded the neighbouring organs (e.g., the bladder and rectum), while sub-stage IVB indicates metastases to remote organs (e.g., the liver or lungs).

Surgical treatment
Cervical cancer in the early stages – that is, a cancer limited to the cervix or a cancer that has spread slightly beyond it but has not invaded the parametria or grown beyond 4 cm – can be treated surgically. The procedure involves removal of the uterus and parametria as well as lymphadenectomy (removal of the lymph nodes located near the primary tumour).
The exception is the microinvasive cancer in stage IA1 (the tumour is not larger than 7 mm and it has not infiltrated the cervix deeper than 3 mm). In such cases, the procedure is limited to simple removal of the uterus. Sometimes, not even that is necessary. Women who want to retain fertility can undergo conization – i.e., partial removal – of the cervix.
Fertility can be retained also by some of the patients in the other early sub-stages of cervical cancer. The treatment in such cases involves complete removal of the cervix, parametria, and neighbouring lymph nodes; however, the uterus remains intact. Over 20% of patients who undergo such treatment are later able to get pregnant and have children.
The effectiveness of surgical treatment of cervical cancer in the early stages is high – approx. 80% of patients make full recovery.
Very rarely, e.g., in the case of a single, operable metastasis, metastasized cervical cancer can also be treated surgically.
In certain cases, if there are factors indicating that the risk of a relapse is particularly high for a patient, the doctor might recommend chemotherapy as adjuvant treatment.

Chemoradiotherapy
Except for the early stages and stage IVB (metastatic cancer), cervical cancer is treated predominantly with chemoradiotherapy, which combines three treatments:
- chemotherapy,
- standard radiotherapy (high, radical dose of ionizing radiation),
- brachytherapy (applying a radiation source inside a patient’s body; the source is placed in the direct vicinity of the cancerous lesion).
The therapy lasts about 8 weeks. It cures more than half of stage II cervical cancers, a third of those in stage III, and, unfortunately, only a few percent of those in stage IVA.
Patients whose overall physical condition prohibits them from undergoing chemotherapy receive only radiotherapy, the results of which are considerably worse.

Chemotherapy:
If the cancer has already metastasized, usually only chemotherapy is administered as palliative treatment – that is, treatment which can stop the progression of the disease for a while but can never cure it.
Cervical cancer is not a chemosensitive tumour; therefore, chemotherapy rarely produces good results.

Remember:
- Cervical cancer can be cured with surgery and chemoradiotherapy.
- Certain forms of surgical treatment allow young women with early-stage cervical cancer to retain fertility.
The chances of curing cervical cancer decrease proportionally to the progression of the disease. The earlier the diagnosis and treatment, the bigger chance there is for surviving cervical cancer.

During the first 2 years after the end of active treatment for cervical cancer the patient should visit her gynaecologist for a follow-up every 3 months. The visit will include:
- a complete gynaecological examination,
- a Pap test.
Other tests are used only when a local recurrence or a metastatic disease are suspected.
For the following 3 years, the follow-up visits should occur every 6 months and after that, once a year.

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