Cervical cancer (cervical cancer) is the most common gynecological malignancy. The high incidence age of in situ cancer is 30~35 years old and invasive cancer is 50~55 years old. In recent 40 years, due to the common application of cervical cytology screening, cervical cancer and precancerous lesions can be detected and treated early, and the incidence and mortality rate of cervical cancer have been significantly reduced.
1.Etiology and pathogenesis
The causes are not fully understood, but may be related to the following factors.
Sexual behavior and number of births: Sexual activity, first sexual intercourse <16 years old, early childbirth and multiple births are closely related to the occurrence of cervical cancer. The development of the cervix in adolescence is immature and more sensitive to carcinogens. The number of childbirth increases, cervical trauma also increases, and there are changes in endocrine and nutrition in childbirth and pregnancy, which increase the risk of developing cervical cancer; the immunity of pregnant women is lower, and the detection rate of hpv-dna is high. Women who have sexual contact with men who have penile cancer, prostate cancer or whose sexual partners have had cervical cancer are also vulnerable to cervical cancer.
Viral infection: High-risk HPV infection is a major risk factor for cervical cancer. 90% or more of cervical cancers are associated with high-risk HPV infection. There are more than 120 known subtypes of HPV, among which subtypes 6, 11, 42, 43 and 44 are low-risk and generally do not induce cancer; subtypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56 or 58 are high-risk. High-risk HPV subtypes produce E6 and E7 oncoproteins, which bind to oncogenes P53 and Rb in host cells, leading to cell cycle dysregulation and carcinogenesis.
In addition, herpes simplex virus type II and human cytomegalovirus may also have a relationship with cervical carcinogenesis. Others: There is some protection for those who apply barrier contraceptive method. Smoking can increase the effect of HPV infection.
2.Classification
The clinical staging criteria of the International Federation of Gynecology and Obstetrics (FIGO) are used. Clinical staging is performed before treatment and is not changed after treatment.
FIGO clinical staging of cervical cancer
O stage in situ carcinoma (pre-infiltrative carcinoma) Ⅰ stage official cervical carcinoma confined to the uterus (extension to the official body will be ignored) ⅠA stage microscopic infiltrative carcinoma, all lesions visible to the naked eye, including superficial infiltration, are ⅠB ⅠA1 interstitial infiltration depth <3mm, horizontal spread ≤7mm ⅠA2 interstitial infiltration depth 3-5mm, horizontal spread ≤7mm ⅠB stage naked eye visible carcinoma foci confined to the cervix, or microscopic lesions > IA2 ⅠB1 maximum diameter of carcinoma visible to the naked eye ≤4cm ⅠB2 maximum diameter of carcinoma visible to the naked eye >4cm Stage II tumor beyond the uterus, but not reaching the pelvic wall or not reaching the lower 1/3 of the vagina IIA without paraphernalia infiltration IIB with paraphernalia infiltration Stage III tumor extending to the pelvic wall and/or involving the lower 1/3 of the vagina and/or causing hydronephrosis or renal nonfunction IIIA tumor involving the lower 1/3 of the vagina.
No extension to the pelvic wall IIIB tumor extended to the pelvic wall and/or caused hydronephrosis or renal non-functioning stage IVA tumor invaded the bladder mucosa or rectal mucosa and/or beyond the true pelvis stage IVB distant metastasis 3 pathology squamous cell invasive carcinoma accounted for 80%~85% of cervical cancer.
3.Macroscopic examination
Microscopic infiltrating carcinoma has no obvious abnormalities when observed by the naked eye, or resembles ectopic cervical columnar epithelium. With the development of lesions, four types can be formed. Ectopic type: the most common type, the cancer foci grow outward in papillary or cauliflower-like shape, with brittle tissue and bleeding easily when touched. It often involves the vagina. Endogenous type: The cancer foci infiltrate deeper into the cervical tissues, the surface of the cervix is smooth or there is only columnar epithelium ectopic, the cervical hypertrophy becomes hard and barrel-shaped. It often involves the parametrial tissue.
4.Clinical manifestations
Early stage cervical cancer often has no obvious symptoms and signs, and the cervix may be smooth or difficult to distinguish from cervical columnar epithelial ectopic. Cervical canal type patients are easily missed or misdiagnosed because of normal cervical appearance. As the lesion progresses, the following manifestations may occur.
Symptomatic vaginal bleeding: early stage is mostly contact bleeding; late stage is irregular vaginal bleeding. The amount of bleeding varies according to the size of the lesion and the invasion of the interstitial blood vessels, and can cause hemorrhage if it erodes large blood vessels. Young patients may also show prolonged menstrual period and increased menstrual flow; elderly patients often have irregular vaginal bleeding after menopause. Generally, exophytic cancer bleeds earlier and more frequently; endophytic cancer bleeds later.
Vaginal discharge: Most patients have white or bloody vaginal discharge, thin like water or rice slop, with fishy odor. In advanced stage, due to necrosis of cancer tissue with infection, there may be large amount of rice-soup-like or purulent foul-smelling leukorrhea. Late symptoms: Different secondary symptoms may appear according to the extent of cancer involvement.
Such as frequent urination, urgent urination, constipation, swelling and pain of lower limbs, etc.; if the cancer presses or involves ureter, it may cause ureteral obstruction, hydronephrosis and uremia; in late stage, there may be anemia, cachexia and other symptoms of systemic failure. In situ carcinoma and micro-infiltrating carcinoma may have no obvious foci, and the cervix may be smooth or only columnar epithelial ectopic. Different signs may appear as the disease progresses. The exophytic type of cervical cancer may show polyp-like or cauliflower-shaped superfluous organisms, often accompanied by infection, with brittle texture and easy bleeding; the endophytic type shows cervical hypertrophy, hard texture and dilated cervical canal; in advanced stage, the cancer tissue is necrotic and falls off, forming ulcers or cavities with bad odor. When the vaginal wall is involved, superfluous growth or hardening of the vaginal wall can be seen; when the parametrial tissue is involved, thickened, nodular, hard or frozen pelvic tissue can be detected by double or triple examination.
5.Examination
Cervical scraping cytology: It is the main method of cervical cancer screening and should be taken in the transformation zone of the cervix. Cervical iodine test: The normal cervical vaginal squamous epithelium is rich in glycogen, which appears brown or dark brown after staining with iodine solution, while the non-staining area indicates that the epithelium there lacks glycogen and may have lesions. Biopsies taken from the iodine non-stained area can improve the diagnostic rate.
Colposcopy: Cervical biopsy should be performed under colposcopic observation for cervical biopsy of suspicious cancerous areas when the cytology of cervical smear is Pap grade III or above and TBS classification is squamous intraepithelial neoplasia. Cervical and cervical canal biopsy: It is a reliable basis for the diagnosis of cervical cancer and cervical precancerous lesions. The tissue taken should include interstitial and adjacent normal tissues. If the cervical smear is positive but the cervix is smooth or the cervical biopsy is negative, a small spatula should be used to scratch the cervical canal and the scrapings should be sent for pathological examination. Cervical conization: For those with multiple positive cervical smears and negative cervical biopsies; or those with cervical intraepithelial neoplasia on cervical biopsy who need to exclude invasive cancer. Cold knife excision, loop electric excision or condensing electric knife excision can be used.
6.Diagnosis
Diagnosis can be confirmed based on medical history, symptoms and examination and cervical biopsy. After diagnosis, chest X-ray, intravenous pyelogram, cystoscopy, proctoscopy, B-type ultrasonography and CT, MRI, PET and other imaging examinations are selected according to specific conditions.
Cervical smear cytology is the main method of cervical cancer screening and should be taken at the cervical transformation zone (see section I). Cervical iodine test Normal cervical vaginal squamous epithelium is rich in glycogen, which is brown or dark brown after staining with iodine solution; non-stained area indicates lack of glycogen in the epithelium there. There may be lesions. Biopsy of the iodine non-stained area may improve the diagnosis. Colposcopic examination of cervical scrapings with Pap grade III or higher and TBS classification of squamous intraepithelial neoplasia should be performed under colposcopic observation by selecting the suspected cancerous area for cervical biopsy.
Biopsy of the cervix and cervical canal is the most reliable basis to confirm the diagnosis of cervical cancer and cervical precancerous lesions. If there are obvious lesions in the cervix, biopsies can be taken from the cancerous lesions. If there is no obvious cancer suspicious area in the cervix, biopsies can be taken at the transformation zone 3, 6, 9 and 12 points 4 or under iodine test or colposcopy for pathological examination. The tissue taken should include interstitial and adjacent normal tissues.
If the abdominal cervical scraping is positive but the official neck is smooth or the cervical biopsy is negative, the cervical canal should be scratched with a small scraper and the scrapings sent for pathological examination. Cervical conization is suitable for those with multiple positive cervical scrapings and negative cervical biopsies; or those with cervical biopsies of carcinoma in situ requiring confirmation. Cold knife excision, loop electric excision (LEEP) or condensing electric knife excision can be used, and the excised tissues should be examined by continuous pathological section (24~36 sheets).
7.Differential diagnosis
It is mainly based on cervical biopsy to differentiate from various cervical lesions with clinically similar symptoms or signs. Including.
Benign cervical lesions: ectopic columnar epithelium of the official cervix, cervical polyps, endometriosis of the cervix and tuberculous ulcers of the cervix; benign cervical tumors: submucosal leiomyoma of the official cervix, cervical canal leiomyoma, cervical papilloma, etc.; malignant cervical tumors: primary malignant melanoma, sarcoma and lymphoma, metastatic carcinoma, etc.
8.Treatment
Appropriate individualized treatment plan is formulated according to clinical stage, patient’s age, fertility requirements, general condition, medical technology level and equipment conditions. A comprehensive treatment plan based on surgery and radiotherapy, supplemented by chemotherapy, is adopted.
Surgery The advantage of surgery is that the ovaries and vaginal function can be preserved in young patients. It is mainly used for patients with early-stage cervical cancer (stage IA~IIA) stage IA1: total hysterectomy; stage IA2: modified radical hysterectomy and pelvic lymph node dissection; stage IB~ⅠA: radical hysterectomy and pelvic lymph node dissection; for those with cancer metastasis in the common iliac lymph nodes, abdominal para-aortic lymphadenectomy or sampling is performed. Young patients with normal ovaries can be preserved. For young patients who require preservation of fertility function. For stage ⅠA1, conical resection of official neck is feasible; for stage ⅠA2~ⅠB1, radical resection of official neck and pelvic lymphadenectomy is feasible for tumor diameter <2cm.
Radiation therapy is suitable for: stage IIB~IV patients; early stage patients whose systemic condition is not suitable for surgery; preoperative radiotherapy for large lesions of the organ and neck; adjuvant therapy for high-risk factors found in pathological examination after surgical treatment. Radiotherapy includes intracavitary irradiation and extracorporeal irradiation. Intracavitary irradiation uses post-mounted treatment machines with radiation sources such as 137 cesium (Cs) and 192 iridium (Ir). It is used to control the local primary lesion. Extracorporeal irradiation mostly uses linear gas pedals, 60 cobalt (Co), etc., to treat paracervical and pelvic lymph node metastases. Local intracavitary irradiation is used mainly in early cases. Extracorporeal irradiation is supplemented; in late stage, extracorporeal irradiation is mainly used, and intracavitary irradiation is supplemented. Chemotherapy is mainly used for patients with advanced stage or recurrent metastases, and in recent years, it is also used for preoperative intravenous or arterial infusion chemotherapy to shrink tumor lesions and control subclinical metastases, and also for radiotherapy sensitization.
Commonly used anti-cancer drugs include cisplatin, carboplatin, bleomycin, mitomycin, isocyclophosphamide, fluorouracil, etc. A platinum-based combination chemotherapy regimen is often used. For example, BVP (bleomycin, vincristine and cisplatin), BP (bleomycin and cisplatin), FP (fluorouracil and cisplatin), TP (paclitaxel and cisplatin), etc. Intravenous or arterial infusion chemotherapy can be used.
9.Prognosis
It is closely related to the clinical stage and pathological type. Those with lymph node metastasis have poor prognosis. Early stage of cervical adenocarcinoma is prone to lymphatic metastasis and has poor prognosis.
After treatment, 50% of recurrence of cervical cancer is within 1 year; 75%~80% is within 2 years. It should be reviewed once every 3 months within 2 years after treatment; once every 6 months within 3~5 years; and once a year from the 6th year. The follow-up includes pelvic examination, vaginal scraping cytology, chest X-ray and blood routine, etc.
10.Prevention
Popularize the knowledge of cancer prevention, carry out sexual health education, and advocate late marriage and less childbirth. Pay attention to high-risk factors and high-risk groups, and seek medical treatment promptly if there are abnormal symptoms. Actively treat sexually transmitted diseases, detect and treat CIN at an early stage, and interrupt the occurrence of cervical invasive cancer. To improve and play the role of women’s cancer prevention and health care network, to carry out cervical cancer screening for early detection, early diagnosis and early treatment. The China Cervical Cancer Prevention and Treatment Project, approved by the Department of Maternal and Child Health and Community Health of the Ministry of Health for a period of 10 years (2007~2016), was officially launched in July 2007. The objectives are to achieve a cervical cancer prevention and treatment awareness rate of more than 90% among the population covered within 10 years; to reduce the incidence of cervical cancer by 50%; and to reduce the mortality rate of cervical cancer by 50%. Recommended optimal screening protocols and general screening protocols. High-risk HPV-DNA testing can be used in combination with cytology methods. Colposcopy and multi-point cervical biopsy should be performed for positive high-risk HPV-DNA, positive cytology, or positive cytology only; negative cytology and positive high-risk HPV-DNA should be followed up at least once a year.