The incidence of cervical cancer is higher in developing countries and backward regions, with more than 100,000 new cases per year in China and about 500,000 new cases worldwide. Transient HPV infection is very common and most of them will be automatically cleared by the body’s superb immunity, while the risk of developing cervical intraepithelial neoplasia and cervical cancer after persistent infection with HR-HPV is much higher than that of the general population. The risk of developing cervical intraepithelial neoplasia and cervical cancer after persistent infection with HR-HPV is much higher than that of the general population. I. Molecular and biological characteristics of HPV HPV is a closed double-stranded epitheliophilic DNA virus with a genome of about 7.9 kb, a molecular weight of 5×106 Daltons, a diameter of 50~55 nm, and no envelope, which is nucleus dormant in nature and can infect different parts of human skin and mucous membrane causing different lesions and is suitable for living in a humid and warm environment. HPV consists of the early phase region (E region), the late phase region (L region) and the long control region (LCR). Studies in molecular biology suggest that the E region (E1, E2, E4-E7) of HPV has the major oncogenes E6 and E7 proteins. E6 blocks apoptosis by inhibiting P53, and E7 can bind to pRb to make the cell cycle runaway, which is an important molecular mechanism for cancer development. The nuclear shell is symmetrical 20-sided and consists of 72 capsids, which are composed of two major capsid proteins, L1 and L2, encoded by the L region, of which L1 accounts for about 80% of the capsid proteins, is highly conserved and specific, has multiple antigenic epitopes, can induce neutralizing antibodies in animals, and is often used as a target antigen for prophylactic vaccines and is the main component in vaccine development. L2 is a minor coat protein with less content and more variation, and can produce cross-reactivity. The LCR region has no coding ability and contains many cellular transcriptional binding sites, which can regulate viral transcription and replication. HPV genotyping characteristics and pathogenic mechanism 1. HPV pathogenicity is related to its subtypes At present, for cervical carcinoma in situ and invasive carcinoma, more than 200 HPV species are identified, mainly based on the DNA homology of the L1 region in the viral genome as the basis for classification. About 40 of these subtypes can infect the genital tract. Some high-risk HPV types with oncogenic potential for cervical cancer are classified. The high-risk types reported in the previous literature basically all contain 17 types including 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66,, 68, 73, 82, and other oncogenic genotypes that are not classified6, 11, etc. Some genotypes have not reached consensus on categorization. Studies have shown that infection with high-risk HPV types can lead to malignant tumors of the reproductive tract. In cervical cancer, persistent infection with HPV 16 and HPV 18 is more common, and HPV 16 is particularly common and has a significantly higher risk of causing cervical lesions than other high-risk types. HPV-18 is another common high-risk HPV type and is more commonly seen in adenocarcinoma. Studies targeting high-risk types are currently available on low-risk HPV types, HPV6 and HPV11, which are generally not associated with malignant lesions and are associated with the vast majority of anal genital warts. Previous studies have shown that positive high-risk HPV types suggest two conditions: a high risk of pre-existing CIN and cervical cancer; an increased risk of CIN and cervical cancer in the next 10 years, while negative HPV predictive values suggest a reduced risk of cervical cancer. 2. Genetic epidemiological evidence on the mechanism of HPV carcinogenesis and cervical cancer susceptibility Studies at home and abroad almost unanimously agree that HPV infection does not necessarily cause cancer, and it takes 5-10 years from HPV infection to cervical cancer production, during which the body’s immunity is enhanced and 80% of infected patients’ viruses can subside on their own, especially in young women, and the risk of disease is mainly dependent on the specific subtypes of HPV, and a series of transitions can occur in this process A series of transitions can occur during this process, and it can be said that cervical cancer is a rare adverse outcome of a common infection. It is believed that the virus enters the cells of the basal layer of the epithelium through micro-incisions in the mucosa of the genital tract. Once HPV has entered the basal cells, the viral capsid is loosened and circular DNA enters the nucleus, where it replicates in the nucleus of the host cell. Replication of viral free DNA in basal cells is relatively tightly regulated and this replication is dependent on the differentiation of epithelial cells. Dominant infection occurs when HPV-infected cells begin to differentiate and move upward within the epithelium, at which point a large number of copies of the HPV gene are produced, dependent on further differentiation of epithelial cells. The virus begins to self-aggregate, completes assembly in the epidermal cells and releases intact viral particles, which can be found on the skin surface when the epidermal cells are shed. the amount of HPV-DNA increases with the severity of cervical lesions and is accompanied by an increased risk of carcinogenesis with increasing viral load. HPV clinical testing and cervical cancer screening To improve the early prevention and treatment of cervical cancer, it is crucial to pay attention to cervical cancer screening and screening methods. Currently, new screening technologies are emerging along with the widespread development of secondary prevention of cervical cancer. There are three available detection methods, the traditional Pap smear (PapSmear) method, which has been significantly reduced in application and is still used in some economically less developed areas, and liquid-based cytology (ThinPreppaptest), which has been developed in the past 10 years or so, both of which have relatively high specificity in screening practice, however, due to the subjective detection method, it is impossible to avoid subjective human factors, which limits its development and promotion. The value of the HR-HPV clinical typing test, which is now widely respected internationally, has been widely accepted and incorporated into primary screening for cervical cancer because of its better negative predictive value, objective experimental method, relatively small human factors, and better reproducibility, which can compensate for the above deficiencies. The United States was the first country to use HPV testing for cervical cancer screening, and in 2003, the U.S. Food and Drug Administration (FDA) approved HPV-DNAHC2 testing combined with liquid-based cytology for primary and screening cervical cancer in women over 30 years of age. 2012, the American Cancer Society ASC, American Society for Colposcopy and Cervical Pathology (ASCCP) and American Society for Clinical Pathology (ASCP ) recommended combined cervical cytology and high-risk HPV testing as cervical cancer screening in a population of women aged 30 to 65 years to maximize the sensitivity of cervical cancer screening. in April 2014, the FDA adopted the first application of HPV testing alone to screen for cervical cancer in women aged 25 years and older, an approach that could directly impact the popularity of cytology in cervical cancer screening, highlighting the importance of high-risk HPV testing in cervical cancer screening. There are two main methods of HR-HPV testing commonly used in China at this stage, one is the more mature hybridization capture (HC2) widely used for quantitative HR-HPVDNA detection; the other is the HPV typing detection by gene chip technology using a combination of polymerase chain reaction (PCR) and reverse dot hybridization (RDB). Since both can provide different information on HPV infection in the reproductive tract of the subject respectively, they are more widely used in the screening and follow-up of cervical diseases. 1. HC2 assay: A qualitative HPV in vitro nucleic acid hybridization assay based on the principle of signal amplification using antibody capture and fluorescent chemical signal technology and genome-wide probes. This method can detect the overall level of DNA of 13 high-risk HPV types (16, 18, 31, 35, 39, 45, 51, 52, 56, 58, 59, 68). studies of combined screening of HR-HPVDNAHC2 with cytology have shown higher positive compliance and accuracy of the combined protocol with pathological examination results, reducing the rate of missed diagnosis. 2.HPV genotyping test: The principle is to take cervical exfoliated cells, PCR in vitro amplification of tissue cell DNA, and then use the human papillomavirus nucleic acid amplification typing test kit, using the nucleic acid molecular rapid hybridization instrument as a platform, according to the principle of import hybridization to make the target molecule cross on the low-density gene chip membrane that has been fixed with nucleic acid probes for rapid hybridization. HPV infection risk factors Studies have shown that the distribution of HPV subtypes is influenced by several factors and changes in different regions, environments and populations, and behaviors such as smoking, age at first sex, and number of sexual partners are important risk factors for HPV infection. In addition, age, education, occupation, economic income, contraceptive methods, number of pregnancies, mode of delivery, number of births, and other infections of the combined reproductive tract may be associated with HPV infection. The focus of research on HPV has shifted in recent years to the relationship between age and viral load and the severity of cervical lesions. Data from large samples of epidemiological surveys have shown that perimenopausal women also have a higher prevalence of high-risk HPV infection.