Cervical cancer
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Cervical cancer is a cancer arising from the cervix.[2] It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body.[12] Early on, typically no symptoms are seen.[2] Later symptoms may include abnormal vaginal bleeding, pelvic pain or pain during sexual intercourse.[2] While bleeding after sex may not be serious, it may also indicate the presence of cervical cancer.[13]
Human papillomavirus infection (HPV) causes more than 90% of cases;[5][6] most people who have had HPV infections, however, do not develop cervical cancer.[3][14] Other risk factors include smoking, a weak immune system, birth control pills, starting sex at a young age, and having many sexual partners, but these are less important.[2][4] Cervical cancer typically develops from precancerous changes over 10 to 20 years.[3] About 90% of cervical cancer cases are squamous cell carcinomas, 10% are adenocarcinoma, and a small number are other types.[4] Diagnosis is typically by cervical screening followed by a biopsy.[2] Medical imaging is then done to determine whether or not the cancer has spread.[2]
HPV vaccines protect against two to seven high-risk strains of this family of viruses and may prevent up to 90% of cervical cancers.[9][15][16] As a risk of cancer still exists, guidelines recommend continuing regular Pap tests.[9] Other methods of prevention include having few or no sexual partners and the use of condoms.[8] Cervical cancer screening using the Pap test or acetic acid can identify precancerous changes, which when treated, can prevent the development of cancer.[17] Treatment may consist of some combination of surgery, chemotherapy, and radiation therapy.[2] Five-year survival rates in the United States are 68%.[18] Outcomes, however, depend very much on how early the cancer is detected.[4]
Worldwide, cervical cancer is both the fourth-most common cause of cancer and the fourth-most common cause of death from cancer in women.[3] In 2012, an estimated 528,000 cases of cervical cancer occurred, with 266,000 deaths.[3] This is about 8% of the total cases and total deaths from cancer.[19] About 70% of cervical cancers and 90% of deaths occur in developing countries.[3][20] In low-income countries, it is one of the most common causes of cancer death.[17] In developed countries, the widespread use of cervical screening programs has dramatically reduced rates of cervical cancer.[21] In medical research, the most famous immortalized cell line, known as HeLa, was developed from cervical cancer cells of a woman named Henrietta Lacks.
Human papillomavirus infection (HPV) causes more than 90% of cases;[5][6] most people who have had HPV infections, however, do not develop cervical cancer.[3][14] Other risk factors include smoking, a weak immune system, birth control pills, starting sex at a young age, and having many sexual partners, but these are less important.[2][4] Cervical cancer typically develops from precancerous changes over 10 to 20 years.[3] About 90% of cervical cancer cases are squamous cell carcinomas, 10% are adenocarcinoma, and a small number are other types.[4] Diagnosis is typically by cervical screening followed by a biopsy.[2] Medical imaging is then done to determine whether or not the cancer has spread.[2]
HPV vaccines protect against two to seven high-risk strains of this family of viruses and may prevent up to 90% of cervical cancers.[9][15][16] As a risk of cancer still exists, guidelines recommend continuing regular Pap tests.[9] Other methods of prevention include having few or no sexual partners and the use of condoms.[8] Cervical cancer screening using the Pap test or acetic acid can identify precancerous changes, which when treated, can prevent the development of cancer.[17] Treatment may consist of some combination of surgery, chemotherapy, and radiation therapy.[2] Five-year survival rates in the United States are 68%.[18] Outcomes, however, depend very much on how early the cancer is detected.[4]
Worldwide, cervical cancer is both the fourth-most common cause of cancer and the fourth-most common cause of death from cancer in women.[3] In 2012, an estimated 528,000 cases of cervical cancer occurred, with 266,000 deaths.[3] This is about 8% of the total cases and total deaths from cancer.[19] About 70% of cervical cancers and 90% of deaths occur in developing countries.[3][20] In low-income countries, it is one of the most common causes of cancer death.[17] In developed countries, the widespread use of cervical screening programs has dramatically reduced rates of cervical cancer.[21] In medical research, the most famous immortalized cell line, known as HeLa, was developed from cervical cancer cells of a woman named Henrietta Lacks.
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Human papillomavirus
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%.[29]
Women who have sex with men who have many other sexual partners or women who have many sexual partners have a greater risk.[30][31]
Of the 150-200 types of HPV known,[32][33] 15 are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), three as probable high-risk (26, 53, and 66), and 12 as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108).[34]
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. Infection with HPV is generally believed 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%.[29]
Women who have sex with men who have many other sexual partners or women who have many sexual partners have a greater risk.[30][31]
Of the 150-200 types of HPV known,[32][33] 15 are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), three as probable high-risk (26, 53, and 66), and 12 as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108).[34]
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. Infection with HPV is generally believed to be required for cervical cancer to occur
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Smoking
Cigarette 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.
Cigarette 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.[37][38][26] Smoking can increase the risk in women a few different ways, which can be by direct and indirect methods of inducing cervical cancer.[37][26][39] A direct way of contracting this cancer is a smoker has a higher chance of cervical intraepithelial neoplasia (CIN3) occurring, which has the potential of forming cervical cancer.[37] 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.[39] Heavy smoking and long-term smoking seem to have more of a risk of getting the CIN3 lesions than lighter smoking or not smoking at all.[40] 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.[26] 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. 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.[36]
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
Long-term use of oral contraceptives is associated with increased risk of cervical cancer. 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.[36]
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
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 (e.g. vinegar) solution to highlight abnormal cells on the surface of the cervix,[5] with visual contrast provided by staining the normal tissues a mahogany brown with Lugol's iodine.[44] 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.
This large squamous carcinoma (bottom of picture) has obliterated the cervix and invaded the lower uterine segment. The uterus also has a round leiomyoma up higher.
Often before the biopsy, the doctor asks for medical imaging to rule out other causes of woman's symptoms. Imaging modalities such as ultrasound, CT scan, and MRI have been used to look for alternating disease, spread of the tumor, and effect on adjacent structures. Typically, they appear as heterogeneous mass on the cervix.[45]
Interventions such as playing music during the procedure and viewing the procedure on a monitor can reduce the anxiety associated with the examination
Treatment
the treatment of cervical cancer varies worldwide, largely due to access to surgeons skilled in radical pelvic surgery, and the emergence of fertility-sparing therapy in developed nations. Because cervical cancers are radiosensitive, radiation may be used in all stages where surgical options do not exist. Surgical intervention may have better outcomes than radiological approaches.[69] In addition, chemotherapy can be used to treat cervical cancer, and has been found to be more effective than radiation alone.[70]
Microinvasive cancer (stage IA) may be treated by hysterectomy (removal of the whole uterus including part of the vagina).[citation needed] For stage IA2, the lymph nodes are removed, as well. Alternatives include local surgical procedures such as a loop electrical excision procedure or cone biopsy.[]
If a cone biopsy does not produce clear margins[73] (findings on biopsy showing that the tumor is surrounded by cancer free tissue, suggesting all of the tumor is removed), one more possible treatment option for women who want to preserve their fertility is a trachelectomy.[74] This attempts to surgically remove the cancer while preserving the ovaries and uterus, providing for a more conservative operation than a hysterectomy. It is a viable option for those in stage I cervical cancer which has not spread; however, it is not yet considered a standard of care,[75] as few doctors are skilled in this procedure. Even the most experienced surgeon cannot promise that a trachelectomy can be performed until after surgical microscopic examination, as the extent of the spread of cancer is unknown. If the surgeon is not able to microscopically confirm clear margins of cervical tissue once the woman is under general anesthesia in the operating room, a hysterectomy may still be needed. This can only be done during the same operation if the woman has given prior consent. Due to the possible risk of cancer spread to the lymph nodes in stage 1B cancers and some stage 1A cancers, the surgeon may also need to remove some lymph nodes from around the uterus for pathologic evaluation.[citation needed]
A radical trachelectomy can be performed abdominally[76] or vaginally[77] and opinions are conflicting as to which is better.[78] A radical abdominal trachelectomy with lymphadenectomy usually only requires a two- to three-day hospital stay, and most women recover very quickly (about six weeks). Complications are uncommon, although women who are able to conceive after surgery are susceptible to preterm labor and possible late miscarriage.[79] A wait of at least one year is generally recommended before attempting to become pregnant after surgery.[80] Recurrence in the residual cervix is very rare if the cancer has been cleared with the trachelectomy.[75] Yet, women are recommended to practice vigilant prevention and follow-up care including Pap screenings/colposcopy, with biopsies of the remaining lower uterine segment as needed (every 3–4 months for at least 5 years) to monitor for any recurrence in addition to minimizing any new exposures to HPV through safe sex practices until one is actively trying to conceive.[citation needed]
Early stages (IB1 and IIA less than 4 cm) can be treated with radical hysterectomy with removal of the lymph nodes or radiation therapy. Radiation therapy is given as external beam radiotherapy to the pelvis and brachytherapy (internal radiation). Women treated with surgery who have high-risk features found on pathologic examination are given radiation therapy with or without chemotherapy to reduce the risk of relapse.[citation needed]
Brachytherapy for cervical cancer
Larger early-stage tumors (IB2 and IIA more than 4 cm) may be treated with radiation therapy and cisplatin-based chemotherapy, hysterectomy (which then usually requires adjuvant radiation therapy), or cisplatin chemotherapy followed by hysterectomy. When cisplatin is present, it is thought to be the most active single agent in periodic diseases.[81] Such addition of platinum-based chemotherapy to chemoradiation seems not only to improve survival but also reduces risk of recurrence in women with early stage cervical cancer (IA2-IIA).[82]
Advanced-stage tumors (IIB-IVA) are treated with radiation therapy and cisplatin-based chemotherapy. On June 15, 2006, the US Food and Drug Administration approved the use of a combination of two chemotherapy drugs, hycamtin and cisplatin, for women with late-stage (IVB) cervical cancer treatment.[83] Combination treatment has significant risk of neutropenia, anemia, and thrombocytopenia side effects.[citation needed]
There is insufficient evidence whether anticancer drugs after standard care help women with locally advanced cervical cancer to live longer.[84]
For surgery to be curative, the entire cancer must be removed with no cancer found at the margins of the removed tissue on examination under a microscope.[85] This procedure is known as exenteration.[85]
No evidence is available to suggest that any form of follow‐up approach is better or worse in terms of prolonging survival, improving quality of life or guiding the management of problems that can arise because of the treatment and that in the case of radiotherapy treatment worsen with time.[86] A 2019 review found no controlled trials regarding the efficacy and safety of interventions for vaginal bleeding in women with advanced cervical ca
Microinvasive cancer (stage IA) may be treated by hysterectomy (removal of the whole uterus including part of the vagina).[citation needed] For stage IA2, the lymph nodes are removed, as well. Alternatives include local surgical procedures such as a loop electrical excision procedure or cone biopsy.[]
If a cone biopsy does not produce clear margins[73] (findings on biopsy showing that the tumor is surrounded by cancer free tissue, suggesting all of the tumor is removed), one more possible treatment option for women who want to preserve their fertility is a trachelectomy.[74] This attempts to surgically remove the cancer while preserving the ovaries and uterus, providing for a more conservative operation than a hysterectomy. It is a viable option for those in stage I cervical cancer which has not spread; however, it is not yet considered a standard of care,[75] as few doctors are skilled in this procedure. Even the most experienced surgeon cannot promise that a trachelectomy can be performed until after surgical microscopic examination, as the extent of the spread of cancer is unknown. If the surgeon is not able to microscopically confirm clear margins of cervical tissue once the woman is under general anesthesia in the operating room, a hysterectomy may still be needed. This can only be done during the same operation if the woman has given prior consent. Due to the possible risk of cancer spread to the lymph nodes in stage 1B cancers and some stage 1A cancers, the surgeon may also need to remove some lymph nodes from around the uterus for pathologic evaluation.[citation needed]
A radical trachelectomy can be performed abdominally[76] or vaginally[77] and opinions are conflicting as to which is better.[78] A radical abdominal trachelectomy with lymphadenectomy usually only requires a two- to three-day hospital stay, and most women recover very quickly (about six weeks). Complications are uncommon, although women who are able to conceive after surgery are susceptible to preterm labor and possible late miscarriage.[79] A wait of at least one year is generally recommended before attempting to become pregnant after surgery.[80] Recurrence in the residual cervix is very rare if the cancer has been cleared with the trachelectomy.[75] Yet, women are recommended to practice vigilant prevention and follow-up care including Pap screenings/colposcopy, with biopsies of the remaining lower uterine segment as needed (every 3–4 months for at least 5 years) to monitor for any recurrence in addition to minimizing any new exposures to HPV through safe sex practices until one is actively trying to conceive.[citation needed]
Early stages (IB1 and IIA less than 4 cm) can be treated with radical hysterectomy with removal of the lymph nodes or radiation therapy. Radiation therapy is given as external beam radiotherapy to the pelvis and brachytherapy (internal radiation). Women treated with surgery who have high-risk features found on pathologic examination are given radiation therapy with or without chemotherapy to reduce the risk of relapse.[citation needed]
Brachytherapy for cervical cancer
Larger early-stage tumors (IB2 and IIA more than 4 cm) may be treated with radiation therapy and cisplatin-based chemotherapy, hysterectomy (which then usually requires adjuvant radiation therapy), or cisplatin chemotherapy followed by hysterectomy. When cisplatin is present, it is thought to be the most active single agent in periodic diseases.[81] Such addition of platinum-based chemotherapy to chemoradiation seems not only to improve survival but also reduces risk of recurrence in women with early stage cervical cancer (IA2-IIA).[82]
Advanced-stage tumors (IIB-IVA) are treated with radiation therapy and cisplatin-based chemotherapy. On June 15, 2006, the US Food and Drug Administration approved the use of a combination of two chemotherapy drugs, hycamtin and cisplatin, for women with late-stage (IVB) cervical cancer treatment.[83] Combination treatment has significant risk of neutropenia, anemia, and thrombocytopenia side effects.[citation needed]
There is insufficient evidence whether anticancer drugs after standard care help women with locally advanced cervical cancer to live longer.[84]
For surgery to be curative, the entire cancer must be removed with no cancer found at the margins of the removed tissue on examination under a microscope.[85] This procedure is known as exenteration.[85]
No evidence is available to suggest that any form of follow‐up approach is better or worse in terms of prolonging survival, improving quality of life or guiding the management of problems that can arise because of the treatment and that in the case of radiotherapy treatment worsen with time.[86] A 2019 review found no controlled trials regarding the efficacy and safety of interventions for vaginal bleeding in women with advanced cervical ca
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