Cervical cancer
Cervical cancer is a type of cancer that develops in the cervix or in any layer of the wall of the cervix. It is due to the abnormal growth of cells that can invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal vaginal bleeding, pelvic pain or pain during sexual intercourse. While bleeding after sex may not be serious, it may also indicate the presence of cervical cancer.
Virtually all cervical cancer cases are linked to genital human papillomavirus infection ; most who have had HPV infections, however, do not develop cervical cancer. HPV 16 and 18 strains are responsible for approximately 70% of cervical cancer cases globally and nearly 50% of high-grade cervical pre-cancers. Minor risk factors include smoking, a weak immune system, birth control pills, starting sex at a young age, and having many sexual partners. Genetic factors also contribute to cervical cancer risk. Cervical cancer typically develops from precancerous changes called cervical intraepithelial neoplasia over 10 to 20 years. About 75% of cervical cancers are squamous cell carcinomas, 20-25% are adenocarcinoma, 3% are adenosquamous carcinomas, and less than 1% are small cell neuroendocrine tumors of the cervix. Diagnosis is typically by cervical screening followed by a biopsy. Medical imaging is then done to determine whether or not the cancer has spread beyond the cervix.
HPV vaccination is the most cost-effective public health measure against cervical cancer. There are six licensed HPV vaccines. They protect against two to seven high-risk strains of this family of viruses. They may prevent up to 90% of cervical cancers. By the end of 2023, 143 countries provided the HPV vaccine in their national immunization schedule for girls. As of 2022, 47 countries also did it for boys. As a risk of cancer still exists, guidelines recommend continuing regular Pap tests. Other methods of prevention include having few or no sexual partners and the use of condoms. Cervical cancer screening using the Pap test or acetic acid can identify precancerous changes, which when treated, can prevent the development of cancer. Treatment may consist of some combination of surgery, chemotherapy, and radiation therapy. Five-year survival rates in the United States are 68%. Outcomes, however, depend very much on how early the cancer is detected.
Worldwide, cervical cancer is both the fourth-most common type of cancer and the fourth-most common cause of death from cancer in women, with over 660,000 new cases and around 350,000 deaths in 2022. This is about 8% of the total cases and total deaths from cancer. 88% of cervical cancers and 90% of deaths occur in low- and middle-income countries and 2% in high-income countries. Of the 20 hardest hit countries by cervical cancer, 19 are in Africa. In low-income countries, it is one of the most common causes of cancer death with an incidence rate of 47.3 per 100,000 women. In developed countries, the widespread use of cervical screening programs has dramatically reduced rates of cervical cancer. In medical research, the most famous immortalized cell line, known as HeLa, was developed from cervical cancer cells of a woman named Henrietta Lacks.
17 November is the Cervical Cancer Elimination Day of Action. The date marks the day in 2020 when WHO launched the Global strategy to accelerate the elimination of cervical cancer as a public health problem, with a resolution passed by 194 countries. To eliminate cervical cancer, all countries must reach and maintain an incidence rate of below 4 per 100 000 women.
Signs and symptoms
The early stages of cervical cancer may be completely free of symptoms. Vaginal bleeding, contact bleeding, or a vaginal mass may indicate the presence of cervical cancer. Also, moderate pain during sexual intercourse and vaginal discharge are symptoms of cervical cancer. Bleeding after douching or after a pelvic exam is a common symptom of cervical cancer. In advanced disease, metastases may be present in the abdomen, lungs, or elsewhere.Symptoms of advanced cervical cancer may include loss of appetite, weight loss, fatigue, pelvic pain, back pain, leg pain, swollen legs, heavy vaginal bleeding, bone fractures, and leakage of urine or faeces from the vagina. Other signs of locally advanced disease include hydronephrosis with flank pain as the ureters directing urine from the kidneys to bladder are blocked, leg swelling and blood clots in the legs as pelvic veins are blocked, rectal bleeding, and bleeding in the urine.
Causes
Infection with some types of HPV is the greatest risk factor for cervical cancer, followed by smoking. HIV infection is also a risk factor. Not all of the causes of cervical cancer are known, however, and several other contributing factors have been implicated.Human papillomavirus
is thought to be required for cervical cancer to occur. HPV types 16 and 18 are the cause of 75% of cervical cancer cases globally, while 31 and 45 are the causes of another 10%.Women who have multiple sexual partners, or have partners who have multiple sexual partners, regardless of sex, are at higher risk of cervical cancer.
Over 200 types of HPV known, 12 are classified as high-risk types, three as probable high-risk, and 12 as low-risk. Most cases of squamous cell carcinomas of the cervix are due to HPV type 16 and most cases of adenocarcinoma are due to HPV type 18. High risk HPV viral subtypes can integrate their DNA into the host genome and induce transcription of the viral cancer causing proteins E6 and E7. E6 degrades the tumor suppressing protein p53 and E7 degrades and inactivates the tumor suppressing protein pRb. The loss of p53 and pRb leads to increased blood vessel growth feeding tumors, loss of tumor cell suppression and cell cycle regulation disruptions, all of which can lead to cervical cancer.
Genital warts, which are a form of benign tumor of epithelial cells, are also caused by various strains of HPV. However, these serotypes are usually not related to cervical cancer. Having multiple strains at the same time is common, including those that can cause cervical cancer along with those that cause warts.
Smoking
, both active and passive, increases the risk of cervical cancer. Among HPV-infected women, current and former smokers have roughly two to three times the incidence of invasive cancer. Passive smoking is also associated with increased risk, but to a lesser extent.Smoking has also been linked to the development of cervical cancer. Smoking can increase the risk in women a few different ways, which can be by direct and indirect methods of inducing cervical cancer. A direct way of contracting this cancer is that someone who smokes has a higher chance of cervical intraepithelial neoplasia occurring, which has the potential of forming cervical cancer. When CIN3 lesions lead to cancer, most of them have the assistance of the HPV virus, but that is not always the case, which is why it can be considered a direct link to cervical cancer. Heavy smoking and long-term smoking seem to have a higher risk of getting the CIN3 lesions than lighter smoking or not smoking at all. Although smoking has been linked to cervical cancer, it aids in the development of HPV, which is the leading cause of this type of cancer. Also, not only does it aid in the development of HPV, but also if the woman is already HPV-positive, she is at an even greater likelihood of contracting cervical cancer.
Oral contraceptives
Long-term use of oral contraceptives is associated with increased risk of cervical cancer in women who have had HPV. Women who have used oral contraceptives for 5 to 9 years have about three times the incidence of invasive cancer, and those who used them for 10 years or longer have about four times the risk.Multiple pregnancies
Having many pregnancies is associated with an increased risk of cervical cancer. Among HPV-infected women, those who have had seven or more full-term pregnancies have around four times the risk of cancer compared with women with no pregnancies, and two to three times the risk of women who have had one or two full-term pregnancies.Diagnosis
Biopsy
The Pap test can be used as a screening test, but it produces a false negative in up to 50% of cases of cervical cancer. Another concern is the cost of doing Pap tests, which makes them unaffordable in many areas of the world.Confirmation of the diagnosis of cervical cancer or precancer requires a biopsy of the cervix. This is often done through colposcopy, a magnified visual inspection of the cervix aided by using a dilute acetic acid solution to highlight abnormal cells on the surface of the cervix, with visual contrast provided by staining the normal tissues a mahogany brown with Lugol's iodine. Medical devices used for biopsy of the cervix include punch forceps. Colposcopic impression, the estimate of disease severity based on the visual inspection, forms part of the diagnosis. Further diagnostic and treatment procedures are loop electrical excision procedure and cervical conization, in which the inner lining of the cervix is removed to be examined pathologically. These are carried out if the biopsy confirms severe cervical intraepithelial neoplasia.
Often, before the biopsy, the doctor asks for medical imaging to rule out other causes of a woman's symptoms. Imaging modalities such as ultrasound, CT scan, and MRI have been used to look for alternative disease, spread of the tumor, and effect on adjacent structures. Typically, they appear as heterogeneous masses on the cervix.
Interventions such as playing music during the procedure and viewing the procedure on a monitor can reduce the anxiety associated with the examination.
Precancerous lesions
means the development of abnormal cells on the surface of the cervix. HPV infections cause CIN, but in most cases, it is resolved by the immune system. However, a small percentage of people might develop a more serious CIN, which, if left untreated, can develop into cervical cancer. CIN is often diagnosed during routine Pap smear examination or colposcopy.The naming and histologic classification of cervical carcinoma precursor lesions has changed many times over the 20th century. The World Health Organization classification system was descriptive of the lesions, naming them mild, moderate, or severe dysplasia or carcinoma in situ. The term cervical intraepithelial neoplasia was developed to place emphasis on the spectrum of abnormality in these lesions and to help standardize treatment. For premalignant dysplastic changes, cervical intraepithelial neoplasia grading is used. It classifies mild dysplasia as CIN1, moderate dysplasia as CIN2, and severe dysplasia and CIS as CIN3. More recently, CIN2 and CIN3 have been combined into CIN2/3. These results are what a pathologist might report from a biopsy.
These should not be confused with the Bethesda system terms for Pap test results. Among the Bethesda results: Low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion. An LSIL Pap may correspond to CIN1, and HSIL may correspond to CIN2 and CIN3, but they are results of different tests, and the Pap test results need not match the histologic findings.