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🏥 | Do you know "the cause of cervical cancer"? Investigating awareness of women in their 20s


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Do you know "the cause of cervical cancer"? Investigating awareness of women in their 20s

 
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Approximately 73 in 1 people in their lifetime are diagnosed with cervical cancer (* 1).
 

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Cervical cancer

Cervical cancer(Uterus cancer,British: cervical cancer) IsCervixと 呼 ば れ るuterusOccurs from the exit ofcancer..Malignant epithelial lesions (cancer) that occur there[1].

The frequency of occurrence is high in developing countries.Onset is high in the 20s to 40s, and death is rare under the age of 25, especially in the elderly.The main cause issexual intercourseInfected byHuman papillomavirus There is a (HPV) infection.Although HPV is usually eliminated by immunity in most people, persistent infections can occur, increasing the risk of cervical cancer.HPV infection has been confirmed in 87.4% of people with cervical cancer[2]..Survival is higher than cancers in other parts of the body, and screening can reduce mortality by up to 80%.

Since the progression is slow, a diagnosis such as every 3 years is recommended, and a diagnosis is made when a test is required."Mother killer (mother killer)Mother killer) ”. As of 2021, about 3000 people die from cervical cancer every year in Japan (2018 diagnoses in 10,978, 2019 deaths in 2,921).[3][4][5][6][7].

Epidemiology

2007 yearswho According to a (WHO) report, it is estimated that about 50 people worldwide develop cervical cancer annually and about 27 die.The frequency of cervical cancer is high in Africa, South Asia, Southeast Asia, Latin America, and the Caribbean coast.[2].

According to the data released by the Japan Society of Obstetrics and Gynecology in 2018, the number of cervical cancer patients in Japan per year is about 1, and the number of deaths is about 1.[9].

The prevalence of cervical cancer by age increases from the late 20s to around 40 and then level off.[10]..Recent changes in the total number of uterine cancers in Japan show an increase in the number of uterine cancers under 39 years old (most uterine cancers under 39 years old are cervical cancers, and most endometrial cancers are 40 years old. Occurs after age).Under the age of 39, cervical cancer has the second highest prevalence after breast cancer.

The main deceased group is the elderly.According to the 2010-2012 death data in the United Kingdom, there are seven deaths a year from cervical cancer under the age of 25, but 7 deaths aged 65 and over, accounting for more than half of all age groups.[11]..According to Japanese data, the number of deaths peaks, especially around the age of 80.[2].

Higher survival rate than cancer in other parts of the body[12]..It progresses slowly, with a survival rate of 95% if cervical cancer is treated early, and a survival rate close to 100% before that.[13].

In January 2021, the National Cancer Research Center, a national research and development corporation, found that a baby with cervical cancer in her mother's cervical cancer was caused by inhaling sheep's water mixed with cancer cells from her mother's cervical cancer into her lungs immediately after giving birth. Presented two cases of lung cancer in children due to the transfer of cancer cells to the lungs of children[14].. The first group of boys could be treated with immunotherapeutic agents, while the second group of boys had their lung cancer removed by surgery.It is reported that the two mothers were diagnosed with cancer after and during childbirth and subsequently died.[15].

Cause

The greatest risk factors for some typesHuman papillomavirus (HPV) infection.continuesmokingIs[16], Various other causes are involved[17].

Human papillomavirus

Human papillomavirus types 16 and 18 account for 75% of the world's causes of cervical cancer, and types 31 and 45 account for 10%.[18].

All types of HPV infection have been confirmed in 87.4% of people with cervical cancer in Japan[2]..Reliable PCR / sequence studies show that type 16-18 is detected in nearly 50% of cervical cancers[2]..The predominant site is the area where squamous epithelialization occurs, and about 90% of patients with squamous epithelialized cancer.[1]..CervixSquamous epithelial cancerIs called human papillomavirusTumor virusCaused by an infection.

There are more than 100 types of HPV, which are roughly divided into two types: skin infection type and mucosa infection type.Cervical cancer is called high-risk HPV among mucosal infectious HPVsSexual intercourseInfected by some HPVs are caused by long-term infection.However, there is an onset even if you have no experience of sexual intercourse.

The types of HPV classified as high-risk types are 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82.[19].

In many cases, even if infected with HPV, HPV is eliminated from the body by immunity. Most HPV infections disappear spontaneously within 2 years, but because immunity is difficult to induce, they are infected many times.In about 10% of people, the infection is prolonged (persistent infection). Persistent infection of HPV causes abnormalities (dysplasia) in cervical cells in some of them, and after 10 years or more on average, a small part (1% or less of infected people) has dysplasia. Progresses from cervical cancer.

Other diseases caused by HPV includeCondyloma acuminata,WartsThere is.In addition, due to oral sex with HPV infected people, etc.Oral CancerThere are reports that it increases the risk of.

smoking

Current or past smokers have a two to three times higher risk of invasive cervical cancer, and second-hand smoke is associated with an increased risk but less so.[20].

Other

It is associated with about 5 times the risk when using oral contraceptives for 9 to 3 years and about 10 times over 4 years.[20].

Two to three times more likely to have one or two full-term pregnancies than a woman who has never been pregnant if she is already infected with HPV.[20].


Organization type

Most areCervixOccurs inSquamous epithelial cancerIs.Mucinous adenocarcinoma (derived from cervical columnar epithelium)Squamous epithelial cancerOther than that, there are relatively many. , Serous adenocarcinoma, Adenosquamous carcinoma,Mucoepidermoid cancer, Frosted glass-like cell carcinoma,Adenoid cystic carcinomaand so on.

Sort

Clinical stage classification of cervical cancer (Nissan Women 2011, FIGO 2008)
Progressive stageMessage
I
Cancer is localized to the cervix (whether or not body infiltration is considered)
IA Invasive cancer that can only be diagnosed histologically
Macroscopically obvious lesions, even superficial infiltrationsIBTo be the period.Infiltration shall be such that the measured depth of stromal infiltration is within 5 mm and the spread in the vertical direction does not exceed 7 mm.The depth of infiltration shall not exceed 5 mm as measured from the basement membrane of the superficial epithelium where infiltration is observed.Invasion of the vessel (vein or lymphatic vessel) does not change the stage of progression.
IA1Stroma infiltration depth within 3 mm and spread no more than 7 mm
IA2Stroma infiltration depth exceeds 3 mm but within 5 mm and spread does not exceed 7 mm
IBClinically obvious lesions confined to the cervix, or IA1Things that exceed the period
IB1Lesions less than 4 cm
IB2Lesions over 4 cm
II
Cancer that has spread beyond the cervix but has not reached the pelvic or subvaginal 1/3
IIBCancer has spread to the vaginal wall but not to parauterine tissue
IIB1If the lesion is 4 cm or less
IIB2Lesions over 4 cm
IIB3Those with parauterine tissue infiltration
IIIThe cancer reaches the pelvic wall and there is no non-cancerous part between the cancer and the pelvic wall.
Or the infiltration of the vaginal wall reaches the bottom 1/3
IIIAVaginal wall infiltration reaches the lower third, but not the pelvic wall
IIIBParauterine infiltration reaching the pelvic wall or with hydronephrosis or non-functional kidney
IVCancer that crosses the small pelvic cavity or affects the bladder and rectal mucosa
IVAThose with infiltration of the bladder or rectal mucosa
IVBThings that extend beyond the small pelvic cavity

* [Cervical Cancer Handling Regulations 3rd Edition (2012)]] Japan Cancer Treatment Society[21]More quoted and modified.

symptom

Many lack subjective symptoms at the stage of atypical epithelium, carcinoma in situ, and early invasive cancer[1]..When the cancer progresses to become invasive cancerIllegal bleeding(Contact bleeding) is seen[1].

Medical examination

The most distinctive feature of cervical cancer is that it is a cancer with a clear cause and can be prevented.is thisDysplasiaThis is because (lesions before cervical cancer) can be detected, and the onset of cancer can be prevented by detecting and treating at the stage of dysplasia by regular cervical cancer screening.Mortality can be reduced by up to 80% with screening[13].

(English editionIt is,Useless medical careThe Pap test is mentioned in the Choosing Wisery campaign to control sexual activity, and even if you are sexually active, you do not need to be tested until you are 21 years old, and you need to be tested between 21-65 years old. Every 30 years until the age of 3 and every 5 years after that[22].

Cervical cancer screening rate by country (2010)[23]
CountryScreening consultation rate
米 国85.0%
Germany78.7%
France71.1%
South Korea68.7%
United Kingdom68.5%
Australia56.8%
Japan37.7%

The test method for cervical cancer screening conducted in Japan isCytologyAnd HPV test.BothWHOIt is a test method that has been confirmed to be effective as a screening test for cervical cancer.However, as of 2019, the only screening method that can be recommended for cervical cancer screening in Japan is "cytodiagnosis," and methods that include HPV testing are not recommended as countermeasure-type screening (resident screening).[24].

Cytology

Cytology is a test to determine if there are any abnormal cells that may be suspected of cervical cancer.A test method in which cells collected from the cervix are stained with a dye and observed under a microscope for abnormal cells.The test result is (Japan Maternal Protection Medical Association, CurrentJapan Obstetrician and Gynecologist Association), According to the classification, it was judged as one of the following.

Japanese mother classification
Inspection resultsClassesDescriptionJudgment[25]
negativeIIt is normal.A1
negativeIIAbnormal cells are found but benign.A1
False positiveIIIaAssume mild to moderate dysplasia.C1
False positiveIIIbAssume advanced dysplasia.C1
PositiveIVAssume carcinoma in situ.C1
PositiveVAssume invasive cancer (microinvasive cancer).C1

For class IIIa and above (C1 as judged by the Association for Preventive Medicine of Japan), a detailed examination is performed.The detection rate of cancer or precancerous lesions by cytology is estimated to be about 70%.Other known methods for describing cytological results include the Papanicolaou (Class) classification, WHO classification, and CIN classification.

From 25, the Japan Society of Obstetricians and Gynecologists unified the report to the international standard "Bethesda System 2013 Compliant Cervical Cytology Report Form" (Bethesda System, Medical Association Classification).[25].

HPV inspection

The HPV test is a test to determine the presence or absence of high-risk HPV infection, which is the cause of cervical cancer.A test method to determine HPV infection using cells collected from the cervix as in cytology. A little less than 30% of people over the age of 10 are judged to be HPV positive. The detection rate of cancer or precancerous lesions by HPV test is estimated to be about 95%.When cytology and HPV testing are used together, the detection rate of cancer or precancerous lesions is almost 100%.

Human papillomavirus(HPV) infection is the cause of all cervical cancers[26]..Most women are eliminated from the body within 18 months of infection and become negative.High risk type[27]For people with long-term infections (eg, types 16,18,31,45), HPV affects DNA, so(English editionIs more likely to develop.

英国National Health Service(NHS) has added "HPV triage" to its screening program.This means that if the initial screening test shows borderline results or low-grade abnormal cells, additional tests for HPV will be done. If HPV is shown to be present, it will be called for a retest, but if HPV is not present, resume the normal screening schedule as if there were no abnormalities.[28].

Study on the accuracy of HPV test reports:

  • Sensitivity 88% -91% (when detecting CIN3 or higher)[29], ~ 97% (when detecting CIN2 +)[30]
  • Specificity 73-79% (CIN3 or higher detected)[29], ~ 93% (CIN2 + detection)[30]

Adding a more sensitive HPV test may reduce specificity[31]..With reduced specificity, the result is that the number of false-positive tests increases, and in many women without the disease,ColposcopyIncreased risk of invasive treatment[32] And unnecessary treatment increases.valuablescreeningThe test requires a balance between sensitivity and specificity in order for the person with the disease to be correctly identified.

Regarding the role of HPV testingRandomized controlled trialSo I compared HPV with colposcopy. HPV testing is as sensitive as direct colposcopy and at the same time reduces the number of speculums required[33]..Randomized controlled trials suggest that HPV testing may be done after abnormal cytology or before cervical cytology.[30].

In a study published in 2007,Pup testInflammatory by doingCytokineIt suggests that it may provoke a response, initiate immunological clearance of HPV, and reduce the risk of cervical cancer.Even women who had ever done a Pap test had a low incidence of cancer. A statistically significant decrease in HPV positivity was correlated with the number of Pap tests taken in a lifetime[34].

The HPV test was able to reduce the incidence of cervical intraepithelial neoplasia or cervical cancer detected in subsequent screening tests in a randomized controlled trial of women aged 32-38 years.The relative risk reduction was 41.3%.For patients at similar risk to those in this study (63% had CIN2-3 or cancer), the absolute risk is reduced by 26%. 3.8 patients must be treated for one to benefit (number required for treatment = 1). To adjust for high or low risk results for CIN 3.8-2click here.

With HPV testPap inspectionResults and findings[35]
HPV inspectionPap inspection (Bethesda system)Explanation of cytodiagnosis results[36]Judgment
negativenegativeFindings normal or within normal rangeRe-examination within 5 years
AllnegativeFindings normal or within normal rangeRe-examination within 3 years
negativeMild (English edition(ASC-US)There are changes in the squamous epithelial cells.It is not possible to distinguish between benign and malignant
negativeMild (English edition (LSIL) (HPV infection, mild dysplasia)Mild abnormalities in squamous epithelial cellsRe-examination within 6-12 months
Without inspectionASC-USThere are changes in the squamous epithelial cells.It is not possible to distinguish between benign and malignant
PositivenegativeFindings normal or within normal range
Without inspectionLSILMild abnormalities in squamous epithelial cellsImmediatelyColposcopy
PositiveLSILMild abnormalities in squamous epithelial cells
AllAdvanced(English edition (ASC-H)Changes in squamous epithelial cells, suspected to be malignant
PositiveASC-USThere are changes in the squamous epithelial cells.It is not possible to distinguish between benign and malignant
All(English edition Lesion (HSIL)Severe abnormalities in squamous epithelial cells require immediate medical attention
AllSquamous epithelial cancer Suspicion (SCC)Suspected squamous cell carcinoma requires immediate medical attention
All(English edition (AGC)Changes are seen in the gland cells, and the possibility of malignant changes is suspected, so immediate consultation is required.

In February 2019, as the primary test for cervical cancer in England, compared with liquefied sample cytology (LBC method), the high-risk human papillomavirus (hrHPV) test showed cervical intraepithelial lesion (CIN). The superiority of the hrHPV test was shown, such as a 2% increase in the detection rate of grade 1 or higher (CIN3) and a 3% increase in the detection rate of cervical cancer, so it will be introduced nationwide by the end of 40 in England. Was reported to be aiming for[37][38].

Diagnosis

As a result of the examinationCytologyIf it is determined that a detailed examination is necessary, such as class IIIa or higher or persistent infection with HPV, a detailed examination will be conducted and a final diagnosis will be made.

In the detailed examination, colposcopy (colposcopy) is performed and a magnifying glass (Culpascope) To magnify the surface of the cervical mucosa 5 to 20 times and observe it.[39]..At that time, in order to clarify the lesion, 3% acetic acid is brought into contact with the cervix (acetic acid processing), and changes due to it are also found.[39].

If there is a suspected abnormality in the colposcopy, collect the tissue of that part and collect it.Tissue examinationA pathological examination is performed by (a so-called targeted histological examination).Although cancer is diagnosed and the clinical stage of progression is estimated by this examination histology, it is difficult to confirm carcinoma in situ and early invasive cancer.[40].

Conical resection is used for definitive diagnosis (and treatment) of highly atypical epithelial, carcinoma in situ, and early-stage invasive cancer[40].

In addition, a serological test (SCC) may be performed.[40].

prevention

HPV vaccine

The HPV vaccine can prevent many types of HPV infection that cause cervical, vaginal, and vulvar cancers.Vaccination is recommended from around 12 years old.Also, regularly after vaccinationPup testIs important to receive[41].. Vaccines to prevent HPV infection can be given at public expense without paying for regular vaccinations for girls from 6th grade to 1st grade of high school, but as of 2020, we are considering expanding the scope to boys who are voluntary vaccinations at their own expense. It was decided to do[42].

Periodic inspection

Pup test, HPV test, two tests are very effective in prevention.Pup test(Cervical cytology) is a test in which cells in the cervix are scraped off and microscopically examined to detect cancer cells and precancerous conditions (dysplasia before cancer). The HPV test checks for infection with HPV that causes cervical cancer.It is important to have these tests regularly between the ages of 21 and 65[41].

In America etc.SpeculumThere is a move to recommend self-checking the cervix using[43][44].

Other,Non smoking,コ ン ド ー ムUse of, limiting sexual partners may also reduce the risk of cervical cancer[41].

HPV and sexual activity

HPV is sexual intercourse with infected people (vaginal sexual intercourse, anal sexual intercourse,Oral sex(Including) is likely to be transmitted, but sexual activity is not an essential activity for infection. Since HPV infection occurs through skin-to-skin contact, it can be transmitted without sexual activity (for example, by touching the anus or genital area with an infected hand), and even the same body can move from site to site.Therefore, it is possible to reduce the risk of HPV infection by "not contacting other people with the genitals", but the possibility of infection in other ways cannot be ruled out.[45].

Incorrect perceptions have led to the dissemination of false information related to cervical cancer and sexual activity, in February 2020.Katsuya Takasu"Cervical cancer can be prevented by putting on a condom for a moment."TwitterTweeted and spread, and many medical professionals pointed out an error in this information.[46].

治療

Treatment of dysplasia

Dysplasia is classified into mild dysplasia, moderate dysplasia, and severe dysplasia according to the degree.Carcinoma in situ is treated in the same way as severe dysplasia.

Mild dysplasia is usually not treated because HPV disappears spontaneously and the dysplasia is likely to heal spontaneously.

The treatment of moderate dysplasia in Japan is not constant.Follow-up and / or treatment,Japan Obstetrics and Gynecology Associationの治療指針では、16型、18型、31型、33型、35型、45型、52型、58型は癌化リスクが高く、治療を検討する指針となっている。特に16型、18型、33型のリスクが高い。治療法は病変部位を含め、子宮頸部の一部分を円錐状に切除する円錐切除術[47]Is common.Conization is almost completely cured without removing the uterus, but there is a possibility of recurrence.Postoperative because the uterus can be left妊娠-birthIt is said that there is almost no effect on.

Even in the case of severe dysplasia, treatment is performed by conization or the like.

Treatment for cervical cancer

The advanced stages of cervical cancer are classified into stage 0, stage IA1, stage IA2, stage IB1, stage IB2, stage IIA, stage IIB, stage IIIA, stage IIIB, stage IVA, and stage IVB in order from mild to mild.

Stage 0 (carcinoma in situ) is the stage in which the cancer remains in the mucosal layer and can be completely cured by conization as with dysplasia.However, if there is no desire to raise a baby, total hysterectomy may be performed.

In stage IA, if the degree is mild, the uterus can be left by conization, but if the lesion cannot be removed by conization, total hysterectomy is performed.

In the case of advanced cancer after stage IB, in addition to the uterusOvary,Fallopian tube, Around itLymph nodeOrgans such as are also removed.In Japan, surgery may be performed even in stage III and IV. In stage III, the arteries and veins are cut and removed from the root of the ligament, and in stage IVA, the bladder and rectum are also removed. There is also.

As postoperative treatment for stages IA to IVA, radiation therapy (+ chemotherapy) is given to the intermediate-risk group, and cisplatin and radiation therapy are given to the high-risk group.

For pelvic recurrence or retroperitoneal lymph node recurrence, radiation therapy should be given if radiation therapy has not been given.Surgery should be considered if resection is possible due to recurrence in the pelvis.

Chemotherapy should be considered in patients with recurrence and stage IVB other than the above.Cisplatin + paclitaxel combination therapy is standard, and carboplatin + paclitaxel combination therapy is also used in Japan based on the results of the JCOG0505 study. Based on the results of the GOG240 study, the combined use of bevacizumab will also be considered.

According to the US cervical cancer guidelines, after stage IA2Radiation therapyMonotherapy, radiation therapy after IB2 stagechemical treatmentCombination therapy is recommended.

Only Japan has selected a treatment method such as extensive hysterectomy + subsequent radiation therapy for stage IIb, and in Europe and the United States, treatment for swelling of the lower limbs and treatment for several years after treatment with postoperative irradiation. In consideration of the worsening of lymphedema in the pelvis that may occur during the treatment, definitive radiation therapy (± chemotherapy) with the same or better results is selected.[48]..Radical hysterectomy has the disadvantage that side effects such as ileus, lower limb lymphedema, and dysuria may occur after surgery.[49]..In a multicenter prospective study in Japan from 2004 to 2007, the 3-year survival rate of radiation monotherapy was 95%, which is equivalent to the treatment results in Europe and the United States, demonstrating the safety and efficacy of radiation monotherapy in Japan. rice field.[50][51]

Research case

Vaccines that return the stage of dysplasia are under development, some of which are oral vaccines using lactic acid bacteria.[52].

footnote

[How to use footnotes]

Source

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