Cervical cancer is one of the major malignant tumors that endanger women’s health worldwide and the most common malignant tumor of the reproductive system in Chinese women. Since the 1950s, Pap smears and cervical cancer screening and treatment have been widely carried out in China, which have significantly reduced the incidence and mortality rate of cervical cancer. However, in recent years, due to the increase of human papillomavirus (HPV) infection, the incidence of cervical cancer in China is on the rise again, and the patients tend to be younger. Zhang Youzhong, Gynecologic Oncology, Qilu Hospital, Shandong University
High-risk factors of cervical cancer incidence
(1) Infection factors
1) Human papillomavirus (HPV): At present, domestic and foreign studies have confirmed that HPV is the main cause of cervical cancer. there are more than 100 subtypes of HPV, and squamous cervical cancer is mainly related to types 16, 18 and 31, while adenocarcinoma is mainly related to types 18 and 16. HPV is mainly transmitted through sexual intercourse, skin contact, etc.
2) Herpes simplex virus (HSV): HSV-2 is currently considered to be a synergistic factor in the development of cervical cancer.
3) Other pathogens: cytomegalovirus (CMV), syphilis spirochetes, trichomonas, chlamydia, fungal and other infections may also be related to the development of cervical cancer.
(2) Factors related to sexual life and marriage and childbirth
1) Early sexual life and early marriage: Those who have early sexual life (i.e. sexual life before the age of 16) and early marriage (marriage before the age of 20) are sensitive to the stimulation of carcinogenic factors because their lower reproductive tract is not yet mature, and once they are infected with certain bacteria or viruses, they are prone to cervical cancer.
2) Multiple sexual partners, active sex life, unclean sex life: increase the chance of invasion of HPV, HSV-2, CMV, etc. and lead to higher incidence of cervical cancer.
3) Premature birth, multiple births and close births: cervical laceration, erosion, cervical ectropion and chronic cervicitis caused by childbirth increase the risk of cervical cancer.
4) Male sexual behavior and related factors: women whose spouses have a history of STD, extramarital sexual partners, and HPV infection have a high incidence of cervical cancer. In addition, men whose ex-wives have had cervical cancer are at high risk, and the incidence of cervical cancer is significantly higher in women who have sexual contact with them.
(3) Chronic cervical diseases
Chronic cervical diseases such as chronic cervicitis, cervical warts and postpartum cervical laceration may be related to cervical cancer and have the potential risk of cancer.
(4) Other
The development of cervical cancer is also related to endocrine, circumcision of sexual partner, smoking, economic status, family history of tumor, diet and other factors. Long-term use of oral contraceptives (>4 years) may increase the risk of cervical cancer, while the use of barrier contraceptive methods such as condoms and spermicidal diaphragms may reduce the incidence of cervical cancer.
Cervical precancerous lesions
Cervical intraepithelial neoplasia (CIN) is a general term for precancerous lesions of the cervix, including CIN1, CIN2 and CIN3, of which CIN2-3 is the true meaning of cervical precancerous lesions. If left untreated, about 10% of cervical intraepithelial neoplasia usually progress to cervical cancer after 5-10 years.
Early diagnosis of cervical cancer and precancerous lesions
(1) Medical history: Women with the above-mentioned high-risk factors are the high-risk group for cervical cancer and its precancerous lesions, so they should pay special attention and have regular gynecological examination and cytological examination.
(2) Clinical manifestations
Most of cervical atypical hyperplasia and preclinical carcinoma (carcinoma in situ and early invasive carcinoma) have no special symptoms and signs. Some patients have increased leucorrhea, contact bleeding or irregular vaginal bleeding. In contrast, invasive carcinoma of the cervix generally has symptoms of vaginal bleeding and increased vaginal discharge.
1) Vaginal bleeding: Young patients often show contact bleeding, which occurs after sexual intercourse or gynecological examination. In early stage, the amount of vaginal bleeding is small, which may only be white with blood or vaginal drip-like bleeding; in advanced cases, the lesion is large and shows multiple vaginal bleeding. In addition, young patients may also present with irregular menstruation, such as shortened cycles, prolonged periods and increased menstrual flow; older patients present with irregular vaginal bleeding after menopause.
(2) Vaginal discharge: Most patients with invasive cervical cancer often complain of increased vaginal discharge, which is white or bloody, thin and watery, with fishy odor. In late stage, due to the breakdown of cancer, necrosis and shedding of tissues and secondary bacterial infection, there is often a large amount of purulent or rice-soup-like foul-smelling vaginal discharge.
(3) Physical examination
The correct diagnosis and clinical staging of cervical cancer highly depend on pelvic triad examination, i.e. careful and comprehensive examination of local cervical and adjacent pelvic tissues. Cervical precancerous lesions (CIN) can be smooth or have chronic cervicitis changes such as cervical erosion and cervical polyps during physical examination. With the growth and development of cervical invasive carcinoma, the local signs vary depending on the type. In the exophytic type, the cervical redundancy grows outward in the form of polyps or papillae with irregular surface, and when combined with infection, the surface is covered with grayish exudate and bleeds easily when touched. In the endogenous type, the cervix is enlarged and hard, the cervical canal is enlarged like a barrel, and the surface of the cervix is smooth or has shallow ulcers.
(4) Auxiliary examination
The early diagnosis of cervical cancer depends on various auxiliary examinations, each of which has its own advantages and disadvantages and must complement each other. At present, the combination of cervical cytology + multi-point cervical biopsy (iodine staining or colposcopy) + cervical canal scraping is generally accepted as the early diagnosis method at home and abroad.
(1) Cervical scraping cytology: This method is the most simple and easy to use diagnostic method, and has become the primary screening method for cervical cancer screening at home and abroad. Married or sexually active women should undergo cervical cytology examination regularly. The method of cervical cytology examination in Qilu Hospital adopts the new Pap smear technique (TCT), and the diagnostic standard of cervical cytology examination report adopts the TBS, which is significantly higher than the traditional Pap smear in terms of sensitivity, specificity and accuracy.
2) Colposcopy: Colposcopy is one of the important auxiliary diagnostic methods for CIN and early cervical cancer. Colposcopy is easy to operate, painless for patients, free from cross infection, and can provide reliable biopsy sites and take timely photos to preserve valuable clinical data, so it has the value of being promoted.
(3) Biopsy: The confirmation of CIN and cervical cancer is ultimately based on pathological examination of cervical biopsy. Cervical biopsy should be performed under colposcopic instructions with prior iodine test, and the most heavily lesioned area should be selected and biopsied at multiple points. LEEP biopsy can also be performed under colposcopic instructions.
(4) Cervical canal scraping (ECC): ECC can help to clarify whether there are lesions in the cervical canal or whether the cancer is involved in the canal. The indications are: pre- and post-menopausal women with abnormal cytology or clinically suspicious cancer; lesions extending into the cervical canal; multiple positive or suspicious cytology, negative or unsatisfactory colposcopy and negative microscopic biopsy.
5) Cervical conectomy: Cervical conectomy includes traditional cold knife conectomy (CKC) and loop electrosurgery of the cervix (LEEP or LLETZ). Multi-point biopsy of the cervix cannot completely replace cervical conization, especially for the diagnosis of microinvasive carcinoma (MIC) or excluding invasive carcinoma, which cannot be based on multi-point biopsy.
6) HPV examination
HPV clinical infection and subclinical infection are also included in CIN. HPV clinical infection refers to warts visible to the naked eye, while HPV subclinical infection (SPI) refers to warts that are not visible to the naked eye but are positive on cytology and visible on colposcopy. HPV-DNA testing for women over 30 years of age can be used for cervical cancer screening, ASC-US stratification and post-treatment testing.
7) Other ancillary tests
Chest X-ray, routine blood and urine tests, liver and kidney function tests, intravenous pyelogram, cystoscopy, proctoscopy, and CT, MRI, PET, etc. should be performed after the diagnosis is confirmed.
The early diagnosis of CIN and cervical cancer should be based on the “three-step” procedure of cervical cytology, colposcopy and pathological histological examination. In advanced stage cervical cancer, biopsy can be performed directly when the lesion is obvious.