Cervical cancer is one of the common gynecological malignancies and is the second most common malignancy among women after breast cancer. According to worldwide statistics, about 400,000-500,000 women suffer from cervical cancer every year, and 100,000 women are detected with cervical cancer in China every year. Although cervical cancer has long attracted the attention of medical professionals and the mortality rate has dropped from 36/100,000 to 8/100,000, the number of new cases is still high every year and there is a trend of rejuvenation. Cervical cancer is still one of the main causes of death from cancer in women, which puts forward higher requirements. Screening and prevention of cervical cancer must be emphasized and persisted in order to reduce the incidence and mortality of cervical cancer.
1. Causes and risk factors of cervical cancer
1.1 The etiology of cervical cancer has a long history of research and is related to early marriage, early childbirth, multiple births, multiple abortions and multiple sexual partnerships.
It is related to low literacy level, poor nutrition and cervical inflammation; it is related to the decrease of body immunity caused by long-term use of contraceptive pills; in recent years, it has been studied that it is related to human papillomavirus (HPV) infection, and HPV can be detected through HPV testing on cervical cancer tissues. This proves that the main cause of cervical cancer is infection with HPV virus.
1.2 HPV viruses HPV viruses are variable-linked DNA viruses containing approximately 7900 base pairs and are classified into many types based on their genomic nucleic acid sequences, with some 40 or more types associated with reproductive tract infections. HPV types are classified into high-risk HPV and low-risk HPV according to their cancer risk. high-risk HPV types include HPV16.18.31.35.39.45.52.56.58.59.68 and low-risk HPV types include HPV6.11.41.42.44.81 and so on. The above types of HPV are associated with the occurrence of cervical cancer and cervical intraepithelial lesions (CIN). The highest rate of HPV16.18 infection was found in cervical cancer tissue specimens, with HPV16 accounting for 50% and HPV18 for 14%. HPV16 infection is associated with an increased risk of cervical high squamous epithelial lesion (ASC-H) and cervical cancer.
HPV infection is a sexually transmitted disease, with peak infection at the age of 18-28. HPV16 infection is increased in people who have frequent sex or multiple sexual partners and can be infected with one or more types of HPV at the same time. HPV infection can occur without any obvious symptoms and can disappear on its own after 8-10 months. In case of low immunity, repeated infection, persistence of HPV, especially when infected with high-risk type HPV, it can cause cervical intraepithelial lesions and cervical cancer.
2. Screening for cervical cancer
The main causes and predisposing factors of cervical cancer have been identified, and therefore it is a preventable disease. Through screening
technology, early detection and early treatment can be achieved, and even the disease can be cured.
2.1 Screening methods for cervical cancer
2.1.1 Cytological screening of cervical cancer
2.1.1.1 Cervical exfoliative cytology is the earliest method used for cervical cancer screening. It is a simple and easy method with low cost, and is a practical method for screening in economically less developed countries and regions and large groups. The method involves gently scraping the cells at the squamous epithelial junction of the ectocervix with a wooden spatula, applying them to a slide, fixing them immediately with 95% alcohol, and staining them afterwards. The cells were analyzed and evaluated by the case specialist. Care was taken to avoid vaginal douching and the use of lubricants prior to sampling. If there is secretion on the surface of the cervix, gently wipe it off with a rolling ball before taking the material. Avoid excessive scraping force causing cervical trauma and bleeding, which may affect the results of the reading. The smear should be applied 1-2 times in one direction to avoid repeated smears. The high false-positive rate of cervical scraping cytology is mainly due to the low number of exfoliated cells and mucus in the sampling, which affects the scraping results.
2.1.1.2 Liquid-based cytology (TCT) and automated cytology reading system can compensate for the deficiencies of cervical smear. The method is to use a fine silk brush placed in the cervical canal about 1 cm rotate 4-5 turns and then remove, immediately put the brush into the cell preservation solution, the cervical cells removed from the brush all stay in the preservation solution bottle, remove the mucus and inflammatory cells, avoid the overlap of cells, make the structure of cells in the wave film clear and easy to identify. It improves the detection rate of abnormal cells and avoids missed diagnosis and misdiagnosis. The cytology automatic reading system is to re-screen and confirm the diagnosis of a cell smear from the initial screening. Especially when atypical squamous cells of undetermined significance, atypical squamous cells that cannot exclude highly squamous epithelial lesions and low-grade squamous intraepithelial lesions, the false-positive rate is reduced, the accuracy is improved, and the efficiency is also improved.
2.1.2 HPV detection There are many methods, including cytology, spot blotting, fluorescence in situ hybridization, nucleic acid blotting in situ hybridization, hybridization capture, multiplex polymerase chain reaction amplification, and so on. Among them, hybridization capture method is highly sensitive, specific, simple and inexpensive to operate. The multi-polymerase chain reaction amplification method has high sensitivity, low specificity and high false positive rate.
2.1.3 Naked eye examination method It is to diagnose cervical lesions by applying a chemical solution to the cervix to stain it and directly observing the reaction of the cervical epithelium with the naked eye under the irradiation of ordinary light sources. one method is to use 3-5% glacial acetic acid staining method, referred to as VIA. apply glacial acetic acid for one minute and observe the reaction of the cervical epithelium to glacial acetic acid, the white area is the area with lesions. Another method is to use 5% iodine solution staining, or VILI. after applying iodine solution, the normal cervical epithelium stains mustard yellow, and the unstained area is the lesioned area. According to the color change based on the epithelium, it is not enough to diagnose cervical cancer and should be combined with cytological examination. Although the feasibility of cervical cancer screening by visual observation is low, it is still an effective method for primary screening of cervical cancer in less economically developed areas and areas with limited cytological examination techniques.
2.1.4 Colposcopy Colposcopy is a type of endoscope that allows direct visual observation of magnified cervical epithelial tissue. In order to improve the positive rate of biopsy and diagnostic accuracy, biopsies can be taken from the lesion area with the help of VIA and VILI, followed by ha cytological examination to achieve early detection and treatment.
2.2 Screening program and follow-up of cervical cancer
2.2.1 Screening population According to clinical data, the incidence of cervical cancer before the age of 19 is almost 0, and the incidence of cervical cancer after the age of 70 is low, so the screening population is generally located after 3 years of sexual intercourse to 70 years old.
2.2.2 Screening protocol Based on the above screening methods, it is possible to choose the HPV test + liquid-based cytological examination method is better. This protocol is highly sensitive, specific and has low leakage rate. In the initial screening patients found to be at high risk in colposcopy + cervical biopsy, a clear diagnosis has been made.
2.2.3 Follow-up time The results of the examination are followed up with regular review according to different situations.
If HPV negative and liquid-based cytology is negative, screening can be performed at an interval of 3-5 years;
If HPV-positive and liquid-based cytology is negative, screening should be done once a year;
If HPV negative and liquid-based cytology positive or both, colposcopy + cervical biopsy should be performed and repeated in one year or less if there is no suspicious lesion, and treatment should be performed if positive.
3. Clinical manifestations of cervical cancer Early stage is often asymptomatic and not obviously different from chronic cervicitis. Sometimes the cervix is smooth, especially when the lesion is located in the cervical canal, and the vaginal part of the cervix has normal appearance, so it is easy to be overlooked and misdiagnosed. The main manifestations are (1) vaginal bleeding (2) vaginal discharge (3) pain in advanced stage, painful difficulty in urination and defecation, cachexia, etc. On physical examination, it can be seen that the cervix is smooth or erosion or cauliflower-like swelling or ulcerated. Endophytic cervical cancer can be seen that the cervical canal is thickened and barrel-shaped with foul odor.
4. Prevention Cervical cancer is a malignant tumor with multiple causative factors and HPV infection as the main cause. Therefore, in terms of prevention, one should strengthen exercise, enhance physical fitness and improve resistance to disease; take good contraceptive measures, reduce the number of abortions and reduce cervical trauma and infection. HPV infection is the cause of cervical cancer, but HPV infection is suspected to be self-healing when the body is strong and the immunity is high. However, treatment should be given in case of each high-risk type or simultaneous infection with more than two types of HPV viruses. For cervical inflammation, physical therapy such as laser and cryotherapy is feasible for young women with Ⅰ and Ⅱ degrees of erosion. For those with III degree celiac disease and CIN 1-2, cervical conization is feasible. for young women with CIN 3, cervical conization is performed with cold knife, and pathological examination is performed to cut along for lesions and exclude invasive cancer residues. In older women, hysterectomy is feasible for those who do not need to preserve their reproductive function.
HPV vaccine is divided into prophylactic vaccine and therapeutic vaccine. The role of prophylactic vaccine is to induce the body to produce antibodies to prevent HPV infection. Therapeutic vaccines work by stimulating or inducing an immune response in the body through inoculation, thus inhibiting the virus and killing it. It is currently in clinical trials.