cervical cancer

子宮頚癌

WordNet

1. relating to or associated with the neck
2. of or relating to the cervix of the uterus; "cervical cancer"
3. type genus of the family Cancridae (同)genus Cancer
4. the fourth sign of the zodiac; the sun is in this sign from about June 21 to July 22 (同)Cancer the Crab, Crab
5. (astrology) a person who is born while the sun is in Cancer (同)Crab
6. a small zodiacal constellation in the northern hemisphere; between Leo and Gemini
7. any malignant growth or tumor caused by abnormal and uncontrolled cell division; it may spread to other parts of the body through the lymphatic system or the blood stream (同)malignant neoplastic disease

PrepTutorEJDIC

1. (子宮などの)頚(けい)部の(にできた)
2. 〈U〉〈C〉『がん』 / 〈U〉〈C〉害悪 / 《Cancer》(星座の)カニ座

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/22 07:29:28」(JST)

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Cervical Cancer
Location of cervical cancer and an example of normal and abnormal cells
Classification and external resources
Specialty	Oncology
ICD-10	C53
ICD-9-CM	180
OMIM	603956
DiseasesDB	2278
MedlinePlus	000893
eMedicine	med/324 radio/140
NCI	Cervical cancer
MeSH	D002583

Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on there are typically no symptoms. 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.

Human papillomavirus (HPV) infection appears to be involved in the development of more than 90% of cases; most people who have had HPV infections, however, do not develop cervical cancer. 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. Cervical cancer typically develops from precancerous changes over 10 to 20 years. There are a few types of cervical cancer. About 90% are squamous cell carcinomas, 10% are adenocarcinoma and a small number are other types. Diagnosis is typically by cervical screening followed by a biopsy. Medical imaging is then done to determine whether or not the cancer has spread.

HPV vaccines protect against between two and seven high-risk strains of this family of viruses and may prevent up to 90% of cervical cancers. As there still is a risk of cancer, guidelines recommend continuing regular Pap smears. Other methods of prevention include: never having sex or having few sexual partners and the use of condoms. Cervical cancer screening using the Pap smear or acetic acid can identify precancerous changes which when treated can prevent the development of cancer. Treatment of cervical cancer may consist of some combination of surgery, chemotherapy and radiotherapy. 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 cause of cancer and the fourth most common cause of death from cancer in women. In 2012, it was estimated that there were 528,000 cases of cervical cancer, and 266,000 deaths. This is about 8% of the total cases and total deaths from cancer. Approximately 70% of cervical cancers occur in developing countries. In low income countries it is the most common cause of cancer death. In developed countries, the widespread use of cervical screening programs has dramatically reduced rates of cervical cancer. In medical research, the most famous cell line known as HeLa was developed from cervical cancer cells of a woman named Henrietta Lacks.

Signs and symptoms

The early stages of cervical cancer may be completely free of symptoms. Vaginal bleeding, contact bleeding (one most common form being bleeding after sexual intercourse), or (rarely) a vaginal mass may indicate the presence of malignancy. Also, moderate pain during sexual intercourse and vaginal discharge are symptoms 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/or (rarely) leakage of urine or feces from the vagina.

Causes

In most cases, cells infected with the HPV virus heal on their own. In some cases, however, the virus continues to spread and becomes an invasive cancer.

Cervix in relation to upper part of vagina and posterior portion of uterus., showing difference in covering epithelium of inner structures.

Infection with some types of human papilloma virus (HPV) is the greatest risk factor for cervical cancer, followed by smoking. Other risk factors include human immunodeficiency virus. Not all of the causes of cervical cancer are known, however, and several other contributing factors have been implicated.

Human papillomavirus

Human papillomavirus type 16 and 18 are the cause of 75% of cervical cancer globally while 31 and 45 are the cause of another 10%.

Women who have many sexual partners (or who have sex with men who have had many other partners) have a greater risk.

Of the 150-200 types of HPV known, 15 are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), 3 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).

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. It is common to have multiple strains at the same time, 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.

Smoking

Cigarette smoking, both active and passive, increases the risk of cervical cancer. Among HPV-infected women, current and former smokers have approximately 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. There are a few different ways that smoking can increase the risk in women which can be by direct and indirect methods of inducing cervical cancer. A direct way of contracting this cancer is a smoker has a higher chance of CIN3 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 more of a 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 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 approximately three times the incidence of invasive cancer, and those who used them for 10 years or longer have approximately 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 approximately 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

Cervical cancer seen on a T2 weighted saggital MR image of the pelvis.

Biopsy

The pap smear can be used as a screening test, but is false negative in up to 50% of cases of cervical cancer. Confirmation of the diagnosis of cervical cancer or pre-cancer 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. Medical devices used for biopsy of the cervix include punch forceps, SpiraBrush CX, SoftBiopsy or Soft-ECC.

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 (LEEP) and 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 including ultrasound, CT scan and MRI have been used to different extent in order to look for alternating disease/spread of tumor/effect on adjacent structures. Typically they appear as heterogeneous mass in the cervix.

Precancerous lesions

Histopathologic image (H&E stain) of carcinoma in situ (also called CIN III), stage 0. The normal architecture of stratified squamous epithelium is replaced by irregular cells that extend throughout its full thickness. Normal columnar epithelium is also seen.

Cervical intraepithelial neoplasia, the potential precursor to cervical cancer, is often diagnosed on examination of cervical biopsies by a pathologist. For premalignant dysplastic changes, the CIN (cervical intraepithelial neoplasia) grading is used.

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 (CIS). The term, Cervical Intraepithelial Neoplasia (CIN) was developed to place emphasis on the spectrum of abnormality in these lesions, and to help standardise treatment. 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 smear (cytopathology) results. Among the Bethesda results: Low-grade Squamous Intraepithelial Lesion (LSIL) and High-grade Squamous Intraepithelial Lesion (HSIL). An LSIL Pap may correspond to CIN1, and HSIL may correspond to CIN2 and CIN3, however they are results of different tests, and the Pap smear results need not match the histologic findings.

Cancer subtypes

Histologic subtypes of invasive cervical carcinoma include the following: Though squamous cell carcinoma is the cervical cancer with the most incidence, the incidence of adenocarcinoma of the cervix has been increasing in recent decades.

• squamous cell carcinoma (about 80-85%)
• adenocarcinoma (about 15% of cervical cancers in the UK)
• adenosquamous carcinoma
• small cell carcinoma
• neuroendocrine tumour
• glassy cell carcinoma
• villoglandular adenocarcinoma

Non-carcinoma malignancies which can rarely occur in the cervix include

• melanoma
• lymphoma

Note that the FIGO stage does not incorporate lymph node involvement in contrast to the TNM staging for most other cancers.

For cases treated surgically, information obtained from the pathologist can be used in assigning a separate pathologic stage but is not to replace the original clinical stage.

Staging

Main article: Cervical cancer staging

Cervical cancer is staged by the International Federation of Gynecology and Obstetrics (FIGO) staging system, which is based on clinical examination, rather than surgical findings. It allows only the following diagnostic tests to be used in determining the stage: palpation, inspection, colposcopy, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous urography, and X-ray examination of the lungs and skeleton, and cervical conization.

• Stage 1A cervical cancer

• Stage 1B cervical cancer

• Stage 2A cervical cancer

• Stage 2B cervical cancer

• Stage 3B cervical cancer

• Stage 4A cervical cancer

• Stage 4B cervical cancer

Prevention

Screening

Cervical screening Test Vehicle in Taiwan

Main articles: Cervical screening and Pap test

Checking the cervix by the Papanicolaou test, or Pap smear, for cervical cancer has been credited with dramatically reducing the number of cases of and mortality from cervical cancer in developed countries. Pap smear screening every 3–5 years with appropriate follow-up can reduce cervical cancer incidence by up to 80%. Abnormal results may suggest the presence of pre cancerous changes allowing examination and possible preventive treatment. The treatment of low-grade lesions may adversely affect subsequent fertility and pregnancy. Personal invitations encouraging women to get screened are effective at increasing the likelihood they will do so. Educational materials also help increase the likelihood women will go for screening, but they are not as effective as invitations.

According to the 2010 European guidelines, the age at which to start screening ranges between 20–30 years of age, "but preferentially not before age 25 or 30 years", and depends on burden of the disease in the population and the available resources.

In the United States it is recommended that screening begin at age 21, regardless of age at which a woman began having sex or other risk factors. Pap tests should be done every three years between the ages of 21 and 65. In women over the age of 65, screening may be discontinued if there was no abnormal screening results within the previous 10 years and no history of CIN 2 or higher. HPV vaccination status does not change screening rates. Screening can occur every 5 years between aged 30–65 when a combination of cervical cytology screening and HPV testing is used and this is preferred. However, it is acceptable to screen this age group with a Pap smear alone every 3 years. Screening is not beneficial before age 25 as there is a very low rate of disease. Screening is not beneficial in women older than 60 years if they have a history of negative results.

Liquid-based cytology is another potential screening method. Although it was probably intended to improve on the accuracy of the Pap test, its main advantage has been to reduce the number of inadequate smears from around 9% to around 1%. This reduces the need to recall women for a further smear. The United States Preventive Services Task Force supports screening every 5 years in those who are between 30 and 65 years when cytology is used in combination with HPV testing.

Pap smears have not been as effective in developing countries. This is in part because many of these countries have an impoverished health care infrastructure, too few trained and skilled professionals to obtain and interepret Pap smears, uninformed women who get lost to follow-up, and a lengthy turn-around time to get results. These realities have resulted in the investigation of cervical screening approaches that use fewer resources and offer rapid results such as visual inspection with acetic acid or HPV DNA testing.

Barrier protection

Barrier protection and/or spermicidal gel use during sexual intercourse decreases cancer risk. Condoms offer protection against cervical cancer. Evidence on whether condoms protect against HPV infection is mixed, but they may protect against genital warts and the precursors to cervical cancer. They also provide protection against other STIs, such as HIV and Chlamydia, which are associated with greater risks of developing cervical cancer.

Condoms may also be useful in treating potentially precancerous changes in the cervix. Exposure to semen appears to increase the risk of precancerous changes (CIN 3), and use of condoms helps to cause these changes to regress and helps clear HPV. One study suggests that prostaglandin in semen may fuel the growth of cervical and uterine tumors and that affected women may benefit from the use of condoms.

Abstinence also prevents HPV infection.

Vaccination

There are two HPV vaccines (Gardasil and Cervarix) which reduce the risk of cancerous or precancerous changes of the cervix and perineum by about 93% and 62%, respectively. The vaccines are between 92% and 100% effective against HPV 16 and 18 up to at least 8 years.

HPV vaccines are typically given to women age 9 to 26 as the vaccine is only effective if given before infection occurs. The vaccines have been shown to be effective for at least 4 to 6 years, and it is believed they will be effective for longer; however, the duration of effectiveness and whether a booster will be needed is unknown. The high cost of this vaccine has been a cause for concern. Several countries have considered (or are considering) programs to fund HPV vaccination.

Since 2010, young women in Japan have been eligible to receive the cervical cancer vaccination for free. In June 2013, the Japanese Ministry of Health, Labor and Welfare mandated that, before administering the vaccine, medical institutions must inform women that the Ministry does not recommend it. However, the vaccine is still available at no cost to Japanese women who choose to accept the vaccination.

Nutrition

Vitamin A is associated with a lower risk as are vitamin B12, vitamin C, vitamin E, and beta-carotene.

Treatment

The treatment of cervical cancer varies worldwide, largely due to large variances in disease burden in developed and developing nations, 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.

Microinvasive cancer (stage IA) may be treated by hysterectomy (removal of the whole uterus including part of the vagina). For stage IA2, the lymph nodes are removed as well. Alternatives include local surgical procedures such as a loop electrical excision procedure (LEEP) or cone biopsy. For 1A1 disease, a cone biopsy (aka cervical conization) is considered curative.

If a cone biopsy does not produce clear margins (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. 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, 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.

A radical trachelectomy can be performed abdominally or vaginally and there are conflicting opinions as to which is better. A radical abdominal trachelectomy with lymphadenectomy usually only requires a two to three day hospital stay, and most women recover very quickly (approximately six weeks). Complications are uncommon, although women who are able to conceive after surgery are susceptible to preterm labor and possible late miscarriage. It is generally recommended to wait at least one year before attempting to become pregnant after surgery. Recurrence in the residual cervix is very rare if the cancer has been cleared with the trachelectomy. Yet, it is recommended for women 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.

• Diagram showing the area removed with a posterior exenteration

• Diagram showing the area removed with a total exenteration operation

• Diagram showing the area removed with an anterior exenteration operation

Brachytherapy for cervical cancer

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 in order to reduce the risk of relapse.

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.

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. Combination treatment has significant risk of neutropenia, anemia, and thrombocytopenia side effects. Hycamtin is manufactured by GlaxoSmithKline.

Prognosis

Prognosis depends on the stage of the cancer. There is a high chance of a survival rate around 100% for women with microscopic forms of cervical cancer. With treatment, the 5-year relative survival rate for the earliest stage of invasive cervical cancer is 92%, and the overall (all stages combined) 5-year survival rate is about 72%. These statistics may be improved when applied to women newly diagnosed, bearing in mind that these outcomes may be partly based on the state of treatment five years ago when the women studied were first diagnosed.

With treatment, 80 to 90% of women with stage I cancer and 60 to 75% of those with stage II cancer are alive 5 years after diagnosis. Survival rates decrease to 30 to 40% for women with stage III cancer and 15% or fewer of those with stage IV cancer 5 years after diagnosis.

According to the International Federation of Gynecology and Obstetrics, survival improves when radiotherapy is combined with cisplatin-based chemotherapy.

As the cancer metastasizes to other parts of the body, prognosis drops dramatically because treatment of local lesions is generally more effective than whole body treatments such as chemotherapy.

Interval evaluation of the woman after therapy is imperative. Recurrent cervical cancer detected at its earliest stages might be successfully treated with surgery, radiation, chemotherapy, or a combination of the three. Thirty-five percent of women with invasive cervical cancer have persistent or recurrent disease after treatment.

Average years of potential life lost from cervical cancer are 25.3 (SEER Cancer Statistics Review 1975-2000, National Cancer Institute (NCI)). Approximately 4,600 women were projected to die in 2001 in the US of cervical cancer (DSTD), and the annual incidence was 13,000 in 2002 in the US, as calculated by SEER. Thus the ratio of deaths to incidence is approximately 35.4%.

Regular screening has meant that pre cancerous changes and early stage cervical cancers have been detected and treated early. Figures suggest that cervical screening is saving 5,000 lives each year in the UK by preventing cervical cancer. About 1,000 women per year die of cervical cancer in the UK. All of the Nordic countries have cervical cancer screening programs in place. Pap smear was integrated into clinical practice in the Nordic countries in the 1960s.

Epidemiology

Age-standardized death from cervical cancer per 100,000 inhabitants in 2004.

  no data

  <2.4

  2.4-4.8

  4.8-7.2

  7.2-9.6

  9.6-12

  12-14.4

  14.4-16.8

  16.8-19.2

  19.2-21.6

  21.6-24

  24-26.4

  >26.4

Worldwide

Worldwide, cervical cancer is both the fourth most common cause of cancer and deaths from cancer in women. In 2012, it was estimated that there were 528,000 cases of cervical cancer, and 266,000 deaths. It is the second most common cause of female specific cancer after breast cancer accounting for around 8% of both total cancer cases and total cancer deaths in women. Approximately 80% of cervical cancers occur in developing countries.

United States

An estimated 12,900 new cervical cancers and 4,100 cervical cancer deaths will occur in the United States in 2015. In the United States, it is the 8th most common cancer of women. The median age at diagnosis is 48. Hispanic women are significantly more likely to be diagnosed with cervical cancer than the general population. In 1998, about 12,800 women were diagnosed in the US and about 4,800 died. In 2014 there was an estimated 12,360 new cases were expected to be diagnosed, and about 4,020 were expected to die of cervical cancer. Among cancers of the female reproductive tract it is less common than endometrial cancer and ovarian cancer. The rates of new cases in the United States was 7 per 100,000 women in 2004. Cervical cancer deaths decreased by approximately 74% in the last 50 years, largely due to widespread Pap smear screening. The annual direct medical cost of cervical cancer prevention and treatment prior to introduction of the HPV vaccine was estimated at $6 billion.

EU

In the European Union, there were about 34,000 new cases per year and over 16,000 deaths due to cervical cancer in 2004.

UK

Cervical cancer is the twelfth most common cancer in women in the UK (around 3,100 people were diagnosed with the disease in 2011), and accounts for 1% of cancer deaths (around 920 people died in 2012). With a 42% reduction from 1988-1997 the NHS implemented screening programme has been highly successful, screening the highest risk age group (25–49 years) every 3 years, and those ages 50–64 every 5 years.

Canada

In Canada, an estimated 1,300 women will be diagnosed with cervical cancer in 2008 and 380 will die.

Australia

In Australia, there were 734 cases of cervical cancer (2005). The number of women diagnosed with cervical cancer has dropped on average by 4.5% each year since organised screening began in 1991 (1991–2005). Regular two-yearly Pap tests can reduce the incidence of cervical cancer by up to 90% in Australia, and save 1,200 Australian women dying from the disease each year.

India

In India,the number of people with uterine cervix cancer are rising but overall the age adjusted rates are decreasing. Study have shown that improvement of education in the female population has improved the survival of people with cancers of uterine cervix.

History

• 400 BCE - Hippocrates noted that cervical cancer was incurable
• 1925 - Hinselmann invented the colposcope
• 1928 - Papanicolaou developed the Papanicolaou technique
• 1941 - Papanicolaou and Trout: Pap smear screening began
• 1946 - Aylesbury spatula was developed to scrape the cervix, collecting the sample for the Pap smear
• 1951 - First successful in-vitro cell line, HeLa, derived from biopsy of cervical cancer of Henrietta Lacks
• 1976 - Harald zur Hausen and Gisam found HPV DNA in cervical cancer and genital warts; Hausen later won the Nobel Prize for his work
• 1988 - Bethesda System for reporting Pap results was developed
• 2006 - First HPV vaccine FDA was approved

Epidemiologists working in the early 20th century noted that cervical cancer behaved like a sexually transmitted disease. In summary:

1. Cervical cancer was noted to be common in female sex workers.
2. It was rare in nuns, except for those who had been sexually active before entering the convent. (Rigoni in 1841)
3. It was more common in the second wives of men whose first wives had died from cervical cancer.
4. It was rare in Jewish women.
5. In 1935, Syverton and Berry discovered a relationship between RPV (Rabbit Papillomavirus) and skin cancer in rabbits. (HPV is species-specific and therefore cannot be transmitted to rabbits)

These historical observations suggested that cervical cancer could be caused by a sexually transmitted agent. Initial research in the 1940s and 1950s attributed cervical cancer to smegma (e.g. Heins et al. 1958). During the 1960s and 1970s it was suspected that infection with herpes simplex virus was the cause of the disease. In summary, HSV was seen as a likely cause because it is known to survive in the female reproductive tract, to be transmitted sexually in a way compatible with known risk factors, such as promiscuity and low socioeconomic status. Herpes viruses were also implicated in other malignant diseases, including Burkitt's lymphoma, Nasopharyngeal carcinoma, Marek's disease and the Lucké renal adenocarcinoma. HSV was recovered from cervical tumour cells.

A description of human papillomavirus (HPV) by electron microscopy was given in 1949, and HPV-DNA was identified in 1963. It was not until the 1980s that HPV was identified in cervical cancer tissue. It has since been demonstrated that HPV is implicated in virtually all cervical cancers. Specific viral subtypes implicated are HPV 16, 18, 31, 45 and others.

In work that was initiated in the mid 1980s, the HPV vaccine was developed, in parallel, by researchers at Georgetown University Medical Center, the University of Rochester, the University of Queensland in Australia, and the U.S. National Cancer Institute. In 2006, the U.S. Food and Drug Administration (FDA) approved the first preventive HPV vaccine, marketed by Merck & Co. under the trade name Gardasil.

Society and culture

Australia

In Australia, Aboriginal women are more than five times more likely to die from cervical cancer than non-Aboriginal women, suggesting that Aboriginal women are less likely to have regular Pap tests. There are several factors that may limit indigenous women from engaging in regular cervical screening practices, including sensitivity in discussing the topic in Aboriginal communities, embarrassment, anxiety and fear about the procedure. Difficulty in accessing screening services (for example, transport difficulties) and a lack of female GPs, trained pap smear providers and trained female Aboriginal Health Workers are also issues.

The Australian Cervical Cancer Foundation (ACCF), founded in 2008, promotes 'women’s health by eliminating cervical cancer and enabling treatment for women with cervical cancer and related health issues, in Australia and in developing countries.' Ian Frazer, one of the developers of the Gardasil cervical cancer vaccine, is the scientific advisor to ACCF. Janette Howard, the wife of former Australian Prime Minister John Howard, was diagnosed with cervical cancer in 1996, and first spoke on her battle with the disease in 2006.

United States

A 2007 survey of 3,076 American women found only 40% had heard of HPV infection and less than half of those knew it causes cervical cancer.

References

Further reading

• Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, Zahaf T, Innis B, Naud P, De Carvalho NS, Roteli-Martins CM, Teixeira J, Blatter MM, Korn AP, Quint W, Dubin G (2004). "Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial". Lancet 364 (9447): 1757–65. doi:10.1016/S0140-6736(04)17398-4. PMID 15541448. 
• Peto J, Gilham C, Fletcher O, Matthews FE (2004). "The cervical cancer epidemic that screening has prevented in the UK". Lancet 364 (9430): 249–56. doi:10.1016/S0140-6736(04)16674-9. PMID 15262102. 

External links

• Cervical cancer at DMOZ

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 浸潤子宮頸癌：疫学、危険因子、臨床症状、および診断 invasive cervical cancer epidemiology risk factors clinical manifestations and diagnosis
• 2. 早期子宮頸癌のマネージメント management of early stage cervical cancer
• 3. 子宮頸癌生存者に対するアプローチの概要 overview of approach to cervical cancer survivors
• 4. 局所進行性子宮頸癌のマネージメント management of locally advanced cervical cancer
• 5. 子宮頸癌のスクリーニング screening for cervical cancer

English Journal

• Graphene blended with SnO₂ and Pd-Pt nanocages for sensitive non-enzymatic electrochemical detection of H₂O₂ released from living cells.

• Fu Y1, Huang D1, Li C1, Zou L1, Ye B2.
• Analytica chimica acta.Anal Chim Acta.2018 Jul 19;1014:10-18. doi: 10.1016/j.aca.2018.01.067. Epub 2018 Feb 7.
• PMID 29523247

• Using MRI cell tracking to monitor immune cell recruitment in response to a peptide-based cancer vaccine.

• Tremblay ML1, Davis C1, Bowen CV1,2,3, Stanley O1, Parsons C1, Weir G4, Karkada M5, Stanford MM4,6, Brewer KD1,2,3,7,6.
• Magnetic resonance in medicine.Magn Reson Med.2018 Jul;80(1):304-316. doi: 10.1002/mrm.27018. Epub 2017 Nov 29.
• PMID 29193231

• E7 oncoprotein of human papillomavirus: Structural dynamics and inhibitor screening study.

• Aarthy M1, Kumar D2, Giri R2, Singh SK3.
• Gene.Gene.2018 Jun 5;658:159-177. doi: 10.1016/j.gene.2018.03.026. Epub 2018 Mar 10.
• PMID 29535023

Japanese Journal

• Association of Combined Tobacco Smoking and Oral Contraceptive Use With Cervical Intraepithelial Neoplasia 2 or 3 in Korean Women

• Journal of Epidemiology advpub(0), 2016
• NAID 130005101375

• 臨床の広場 子宮頸癌術後の補助療法について : 現状と今後の展望

• 産婦人科の進歩 67(4), 410-413, 2015-10
• NAID 40020613884

• 子宮頸癌検診細胞診における異形成細胞検出法

• センシングフォーラム資料 32, 171-176, 2015-09-10
• NAID 40020609128

Related Links

• Cervical cancer - Wikipedia, the free encyclopedia

Cervical cancer is the term for a malignant neoplasm arising from cells originating in the cervix uteri. One of the most common symptoms of cervical cancer is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms ...

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リンク元	「子宮頚癌」「cervix cancer」「cancer of the cervix」
関連記事	「cervical」「cancer」

「子宮頚癌」

　　[★]

英

cervical cancer, cancer of the cervix, cancer of the uterine cervix, uterine cervical cancer, endocervical carcinoma

ラ

carcinoma colli uteri

同

子宮頸癌

関

子宮頚部、子宮、腫瘍

概念

• 子宮頚部に発生した癌

疫学

• 95%扁平上皮癌、5%腺癌。腺癌の割合は年々増えてきている。

• 腺癌は若年者で多く、高分化型腺癌である。原因は不明

• 子宮頚癌：子宮体癌＝90：10　←　とにかく子宮頚癌が多い
• 50歳前後

病因

• 子宮頚癌の99%にヒトパピローマウイルス(HPV)が認められ、HPVの関与が大きい。

HPV遺伝子型の16,18型で7割を占める。他のハイリスク型は31,33,35,45,52,58である。

• 感染者の90%が治癒するが、10%は持続感染する。
• 持続感染者の一部が5-10年を経て異形成から子宮頚癌に進展する。

病理

扁平上皮癌

• 扁平-円柱上皮接合部 squamocolumnar junction SCJの円柱上皮下より発生する。この部位に予備細胞があり、この細胞が扁平上皮化生することにより生じる。
• HIV感染により異型細胞(コイロサイトーシス)を生じる。基底細胞に異型細胞が認められればCIN1(下層1/3),CIN2(下層2/3),CIN3(表層以外),CIS(CIN3,全層),微小浸潤癌と進展していく。

腺癌

• 腺上皮類似の細胞より構成され、腺管形成傾向を示す。表層では乳頭状に、深部では腺管形成を示して増殖する。粘液を産生している細胞が認められる。
• 腺癌は手術で根治治療できない場合、放射線や化学療法が奏効しづらく予後不良である。

リスクファクター

• 発展途上国在住、活発な性行動、低所得階級、多産婦、喫煙、ピル、ステロイド、HIV、眼瞼親身受診、他のSTD

症状

• 初期：上皮内癌(臨床進行期では0期)および微小浸潤癌(Ia期)のほとんどが無症状(⇔子宮体癌では不正出血)　←　検診が重要となる　
• 浸潤癌：不正性器出血、接触出血あるいは帯下など
• 周辺臓器浸潤：骨盤痛、血尿、下血

検査

細胞診

• スクリーニング検査として行われる

ベセスダシステム	推定病変	用語説明	日母分類
NILM	非腫瘍性病変, 炎症	陰性	I/II
ASC-US	軽度扁平上皮内病変(LSIL)疑い	意義不明異型扁平上皮	II/IIIa
ASC-H	高度扁平上皮内病変(HSIL)疑い	高度病変を除外できない異型扁平上皮	III/IIIb
LSIL	HPV感染, 軽度異形成	軽度扁平上皮内病変	IIIa
HSIL	中等度異形成, 高度異形成, 上皮内癌	高度扁平上皮内病変	IIIa, IIIb, IV
SCC	扁平上皮癌（微小浸潤含む）	扁平上皮癌	V
AGC	腺異形成, 腺系病変疑い	異型腺細胞	III
AIS	上皮内腺癌	上皮内腺癌	IV
adenocarcinoma	腺癌	腺癌	V
other	その他のがん	その他の悪性腫瘍	V

HPV検査

• スクリーニング検査押して行われる
• 癌または前癌病変の発見率95%。細胞診と組み合わせると発見率は100%。

コルポ診

• コルポスコープと呼ばれる拡大鏡を用いて子宮頚部粘膜表面を拡大し、観察。
• 3-5%の酢酸を子宮頚部に接触させ、それによる変化も所見とする。

画像検査

• MRI

• T2：淡い高信号(中～高信号)。子宮頚部間質は低信号。このコントラスト差を利用して浸潤の程度を把握する。水平断ではstromal ring(子宮内腔を取り囲む低信号)の消失がみられる
• T1Gd造影：腫瘍は低信号となる。周囲組織浸潤を見積もるために使用される

臨床進行期

• 治療前に決定される

出典不明

子宮頸癌	0期(上皮内癌)			上皮内癌	・円錐切除(挙児希望) ・円錐切除or単純子宮全摘術(挙児希望なし)
	I期 子宮頚部に限局	Ia期 微小浸潤癌	Ia1期	(微小浸潤癌) 病理組織 間質浸潤 深さ3mm以内 幅7mmを超えない	・円錐切除(挙児希望) ・単純子宮全摘術(挙児希望なし)
			Ia2期	(微小浸潤癌) 病理組織 間質浸潤 深さ3-5mm以内 幅7mmを超えない	・(準)広汎子宮全摘術+骨盤リンパ節郭清術 ・広汎子宮全摘術
		Ib期	Ib1期	4cm以下	・広汎子宮全摘術
			Ib2期	4cmを超える	・広汎子宮全摘術 ・放射線療法 ・同時科学放射線療法
	II期 頸部を超えて進展かつ 骨盤壁or膣壁下1/3に達しない	IIa期		膣壁浸潤のみ	・広汎子宮全摘術 ・放射線療法 ・同時科学放射線療法
		IIb期		子宮傍組織浸潤のみ	・広汎子宮全摘術 ・放射線療法 ・同時科学放射線療法
	III期 骨盤壁に達するor 膣壁浸潤下1/3	IIIa期		膣壁浸潤下1/3	・放射線療法 ・同時科学放射線療法
		IIIb期		骨盤壁に達する	・放射線療法 ・同時科学放射線療法
	IV期 膀胱,直腸の粘膜へ浸潤or 小骨盤を超えて進展	IVa期		膀胱,直腸の粘膜へ浸潤	・放射線療法 ・同時科学放射線療法
		IVb期		小骨盤を超えて進展	・放射線療法 ・化学療法

妊娠と治療

• 0期(CIN), Ia期：分娩まで経過観察し、分娩後治療(円錐切除もしくは単純子宮全摘術)
• Ib期：原則的に広汎子宮全摘出術　　←　　妊娠継続は母体へのリスクが大きすぎるため(周辺臓器浸潤、転移など？)。

診断

• 診察＋検査で診断する。

• 視診、内診、直腸診、細胞診、コルポスコピー、組織診、尿路系検査、単純X線撮影、超音波検査、CT、MRI、腫瘍マーカー、リンパ管造影、ガリウムシンチグラム。

• 新臨床進行期分類(日産婦1997, FIGO 1994)(参考4)により治療前に病期を決定する。決定の根拠とできる診察＆検査は以下の通りである。触診、視診、コルポスコピー、診査切除、頸管内掻爬、子宮鏡、膀胱鏡、直腸鏡、排泄性尿路造影、肺及び骨のＸ線検査。なお、子宮頸部円錐切除術は臨床検査とみなす。

治療

• 子宮頚部円錐切除　：CIS, Ia
• 単純子宮全摘出術　：CIS, Ia
• 準広汎子宮全摘出術：CIS, Ia
• 広汎子宮全摘出術　：Ib, II, III
• 超広汎子宮全摘出術：IIIb
• 骨盤除臓術　　　　：IVa

放射線療法

• 適応：(1)腫瘍切除後に顕微鏡的に癌の残存が疑われる、(2)リンパ節転移あり、(3)骨盤近くまで浸潤、(4)脈管内浸潤有り、(5)膣摘出不十分 (NGY.223)

QB Q-288

• 外部照射：(Ib1？～II)広汎子宮全摘術後に膣断端陰性
• 外部照射＋腔内照射(遠隔操作式後装填法 RALS)：(Ib1？～II)広汎子宮全摘術後に膣断端陰性、あるいはIII,IV期

ガイドライン2

進行期		外部照射（Gy）		腔内照射（Gy／ 回，A点線量）
		全骨盤	中央遮蔽
Ⅰ		0	45～50	'29／5
Ⅱ	小	0	45～50	'29／5
	大	20	30	'23／4
Ⅲ	小～中	20～30	20～30	'23／4
	大	30～40	20～25	'15／3～20／4
ⅣA		30～50	10～20	'15／3～20／4

総照射線量は進行期によって変わる。ガイドライン2によれば、外部照射は45-70Gyまでありうる。施設ごとに放射線治療のプロトコールは異なる。例えば、参考7を参照すると、外部照射は最大54Gyである。

合併症

ガイドライン2

• 急性期：悪心(放射線宿酔)、下痢、膀胱炎、皮膚炎(特に下方へ延長した照射野を設定した場合の会陰部)、白血球減少症
• 晩発性(grade3以上の頻度)：直腸炎(出血)(5?10%)、膀胱炎(出血)(5%以下)、小腸障害(腸閉塞)(5%以下)皮下組織繊維化・浮腫(下腹部)、腟粘膜の癒着・潰瘍、膀胱腟瘻、直腸腟瘻、骨折、下肢浮腫

予後

参考3

病期	症例数	５年相対生存率
I期	1137	92.1％
II期	447	69.8％
III期	428	48.9％
IV期	151	17.2％

ガイドライン

• 1. 子宮頸癌治療ガイドライン2007年版：

http://www.jsgo.gr.jp/guideline/keigan.html

• 2. 放射線治療計画ガイドライン・2008 - 日本放射線専門医会・医会，日本放射線腫瘍学会，日本医学放射線学会編集

http://www.kkr-smc.com/rad/guideline/2008/

参考

• 1. 癌ブロジェクト

http://www.gan-pro.com/public/cancer/cervical.html

• 3. がん情報サービス

http://ganjoho.jp/public/cancer/data/cervix_uteri.html

• 4. 臨床進行期分類（日産婦1997年、FIGO1994年）

http://plaza.umin.ac.jp/~jsog-go/CC/CC_youkou_main9.htm

• 5. ベセスダシステム

http://www.kawasaki-m.ac.jp/pathology2/pdf/Bethesda-moriya.pdf

• 6. [charged] Invasive cervical adenocarcinoma - uptodate [1]
• 7. 子宮頸癌の進行期別線量配分

http://web.sapmed.ac.jp/radiol/uterus.html

国試

• 105E059：治療。放射線治療を行う際、貧血を改善しないと効果が低下するから輸血すべし、らしい。
• 102I041：コルポスコピー所見で高度の白色上皮を呈する子宮頚部癌上皮内腫瘍(CIN)。細胞診ではクラスIIIb

「cervix cancer」

　　[★]

子宮頚癌、子宮頸癌、子宮頚部癌、子宮頸部癌

関

cancer of the cervix、cancer of the uterine cervix、cervical cancer、cervical carcinoma、cervical neoplasm、cervix carcinoma、cervix neoplasm、endocervical carcinoma、uterine cervical neoplasm、uterine cervix cancer

「cancer of the cervix」

　　[★]

子宮頚癌、子宮頸癌、子宮頚がん、子宮頸がん

関

cancer of the uterine cervix、cervical cancer、cervical carcinoma、cervical neoplasm、cervix cancer、cervix carcinoma、cervix neoplasm、endocervical carcinoma、uterine cervical neoplasm、uterine cervix cancer

「cervical」

　　[★]

• adj.

• 頚部の、頸部の、頚椎の、頸椎の、頚髄の、頸髄の、頚の、頸の、子宮頚部の、子宮頸部の

一般には首を表すが病名では子宮頚部を表すことが多いので注意

関

cervical cord、cervical region、cervical spinal cord、cervical spine、cervical vertebra、cervical vertebrae、cervix、cervix of uterus、cervix uteri、neck、uterine cervix、uterocervical、vertebrae cervicales

　 　 　

「cancer」

　　[★]

同

癌腫

関

tumor