Cervical cancer is the most common gynecological malignancy. The high incidence age of in situ cancer is 30 to 35 years old, and that of invasive cancer is 45 to 55 years old; in recent years, there is a trend of its incidence becoming younger. The common application of cervical cytology screening in recent decades has enabled early detection and treatment of cervical cancer and precancerous lesions, and the incidence and mortality rate of cervical cancer have been significantly reduced.
I. Etiology may be related to the following factors.
1.Viral infection
High-risk HPV infection is the main risk factor for cervical cancer. 90% or more of cervical cancers are associated with high-risk HPV infection.
2.Sexual behavior and number of births
Multiple sexual partners, first sexual intercourse <16 years old, young age at first birth, multiple pregnancies and multiple births are closely related to the occurrence of cervical cancer.
3.Other biological factors
Chlamydia trachomatis, herpes simplex virus type II, trichomonas and other pathogens play a synergistic role in the pathogenesis of cervical cancer caused by high-risk HPV infection.
4.Other behavioral factors
Smoking as a synergistic factor of HPV infection can increase the risk of cervical cancer. In addition, poor nutrition and poor hygiene can also influence the occurrence of the disease.
II. 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. Patients with cervical canal type are easy to be missed or misdiagnosed because of normal cervical appearance. With the development of lesions, the following manifestations may appear.
1.Symptoms
(1) Vaginal bleeding: contact bleeding in the early stage and irregular vaginal bleeding in the middle and late stage. The amount of bleeding varies according to the size of the lesion and the invasion of the interstitial vessels, and may cause hemorrhage if the large vessels are invaded. Younger patients may also present with prolonged periods and increased menstrual flow; older patients often have irregular vaginal bleeding after menopause. Generally, the exogenous type presents with vaginal bleeding earlier and with more bleeding; the endogenous type presents with the symptoms later.
(2) Vaginal discharge: Most patients have vaginal discharge, which is white or bloody, thin like water or rice slop, or smells fishy. In advanced stage, due to necrosis of cancer tissue and infection, there may be large amount of rice-soup-like or pus-like foul-smelling leucorrhea.
(3) Late symptoms: Different secondary symptoms may appear according to the extent of cancer foci 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 the late stage, there may be anemia, cachexia and other symptoms of systemic failure.
2.Signs
Carcinoma in situ and micro-infiltrating carcinoma may have no obvious foci, and the cervix may be smooth or only columnar epithelial ectopic. Different physical signs may appear with the development of the disease. Ectogenous cervical cancer can be seen as polyp-like or cauliflower-like superfluous organisms, often accompanied by infection, and the tumor is brittle and prone to bleeding; endogenous cervical cancer can be seen as cervical hypertrophy, hardness and cervical canal expansion; 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 can be seen on the vaginal wall or the vaginal wall is hardened; when the parametrial tissue is involved, thickened, nodular, hard or frozen pelvic tissue can be found on double or triple examination.
3.Pathological types
(1) Squamous carcinoma: It is classified into grade III according to histological differentiation. Grade Ⅰ is highly differentiated squamous carcinoma, grade Ⅱ is moderately differentiated squamous carcinoma, grade Ⅲ is lowly differentiated squamous carcinoma, which is mostly undifferentiated small cells.
(2) Adenocarcinoma: It accounts for 15%-20% of cervical cancer. There are 2 main histological types.
(1) Mucinous adenocarcinoma: the most common type, which originates from columnar mucus cells of the cervical duct, and can be seen microscopically as glandular structure with multi-layered glandular epithelial cell hyperplasia, obvious heterogeneous hyperplasia, and nuclear schizophrenia, with cancer cells protruding into the glandular lumen in a papillary pattern. It can be divided into high, medium and low differentiated adenocarcinoma.
(2) Malignant adenoma: also known as slightly deviated adenocarcinoma, it is a highly differentiated mucosal adenocarcinoma of the cervical duct. There are many adenocarcinomas with different sizes and variable morphology, with punctate protrusions into the deep interstitial layer of human cervix.
(3) Adenosquamous carcinoma: It accounts for 3% to 5% of cervical cancer. It is formed by the differentiation of reserve cells to both glandular cells and squamous cells. The cancer tissue contains both adenocarcinoma and squamous carcinoma components.
4.Metastasis route
Direct spread and lymphatic metastasis are the main routes of metastasis, while hematogenous metastasis is less common.
(1) Direct spread is the most common, in which the cancer tissue infiltrates locally and spreads to adjacent organs and tissues. It often involves the vaginal wall downward and rarely involves the cervical canal upward to the official cavity; the cancer foci spread to both sides and can involve the paracervical and paravaginal tissues to the pelvic wall; when the cancer foci press or invade the ureter, it can cause ureteral obstruction and hydronephrosis. In late stage, it may spread to the bladder or rectum, forming vesicovaginal fistula or rectovaginal fistula.
(2) Lymphatic metastasis: local infiltration of cancer foci invades lymphatic vessels and forms tumor emboli, which enter local lymph nodes with lymphatic drainage and spread within lymphatic vessels. The primary group of lymphatic metastasis includes parametrium, paracervical, foramen ovale, internal iliac, external iliac, common iliac and presacral lymph nodes; the secondary group includes deep and superficial inguinal lymph nodes and para-aortic lymph nodes.
(3) Hematogenous metastasis is less common, but in advanced stage, it may metastasize to lung, liver or bone, etc.
III. Examination
1.Cervical smear cytology examination
It is the main method of cervical cancer screening and should be taken in the transformation zone of the cervix.
2.Cervical iodine test
The normal cervical vaginal squamous epithelium is rich in glycogen, which is brown or dark brown after staining with iodine solution, while the unstained area indicates that the epithelium lacks glycogen and may have lesions. Biopsy in the iodine non-staining area can improve the diagnosis rate.
3.Colposcopy
Cervical biopsy should be performed under colposcopic observation when the cervical scraping cytology is Pap grade III or above and TBS classification is squamous intraepithelial neoplasia.
4.Cervical and cervical canal biopsy
It is a reliable basis to confirm 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 scraper should be used to scratch the cervical canal and the scrapings should be sent for pathological examination.
5.Cervical conization
It is suitable for those who have repeatedly positive cervical smear and negative cervical biopsy; or those who have cervical intraepithelial neoplasia on cervical biopsy and need to exclude infiltrating cancer. Cold knife excision, loop electric excision or condensing electric knife excision can be used.
IV. Diagnosis
Diagnosis can be confirmed based on medical history, symptoms, gynecological examination and/or colposcopy and cervical tissue biopsy.
Differential diagnosis
Confirmation of diagnosis is based on cervical biopsy. Attention should be paid to differentiate from various cervical lesions with similar clinical symptoms or signs.
1. Benign cervical lesions
Cervical columnar epithelial ectopic, cervical polyp, cervical endometriosis and cervical tuberculous ulcer, etc.
2.Benign cervical tumors
Cervical submucosal leiomyoma, cervical canal leiomyoma, cervical papilloma, etc.
3.Malignant tumors of the cervix
Primary malignant melanoma, sarcoma and lymphoma, metastatic cancer, etc.
VI. Treatment
Appropriate individualized treatment plan is formulated according to the 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
1.Surgical treatment
Surgery is mainly used for early stage cervical cancer patients.
Commonly used surgical procedures include: total hysterectomy; subextensive total hysterectomy and pelvic lymph node dissection; extensive total hysterectomy and pelvic lymph node dissection; abdominal para-aortic lymphadenectomy or sampling. Younger patients with normal ovaries may be preserved. For young patients who require preservation of fertility, conical hysterectomy or radical hysterectomy is feasible in particularly early stage. Different procedures are chosen according to the different stages of the patient.
2.Radiotherapy
①Patients in the middle and late stage.
②Early stage patients whose general condition is not suitable for surgery.
③Pre-operative radiotherapy for large cervical lesions.
④Adjuvant treatment for high-risk factors found in pathological examination after surgical treatment.
3.Chemotherapy
It is mainly used for patients with advanced stage or recurrent metastasis. In recent years, surgery combined with preoperative neoadjuvant chemotherapy (intravenous or arterial infusion chemotherapy) is also used to shrink tumor lesions and control subclinical metastasis, as well as to sensitize radiotherapy. Commonly used chemotherapeutic drugs include cisplatin, carboplatin, paclitaxel, bleomycin, isocyclophosphamide, fluorouracil, etc.
VII. Prognosis
It is closely related to the clinical stage and pathological type. Those with lymph node metastasis have poor prognosis. Early cervical adenocarcinoma is prone to lymphatic metastasis and has a relatively poor prognosis. In conclusion, early treatment has a better prognosis.
Prevention
Popularize the knowledge of cancer prevention, carry out sexual health education, and promote late marriage and less childbirth.
2. Pay attention to high-risk factors and high-risk groups, and seek medical treatment promptly if there are abnormal symptoms.
3. Early detection and treatment of cervical intraepithelial neoplasia and interruption of cervical invasive cancer.
4.Sound and play the role of women’s cancer prevention and health care network, carry out cervical cancer screening, achieve early detection, early diagnosis and early treatment.