Transient HPV infections are very common and most of them are cleared by the body’s superb immunity, while the risk of developing cervical intraepithelial neoplasia and cervical cancer is much higher after persistent infection with HR-HPV than in the general population. 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 infections are very common and most of them are cleared by the body’s superb immunity, while the risk of developing cervical intraepithelial neoplasia and cervical cancer is much higher after persistent infection with HR-HPV than in 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. (A) 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 the 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 symmetric 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, highly specific, has multiple antigenic epitopes, can induce neutralizing antibodies in animals, and is often used as a target antigen for prophylactic vaccines and is a major 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. (2) Genotyping characteristics and pathogenic mechanism of HPV 1. The pathogenicity of HPV is related to its subtypes At present, for in situ and invasive carcinoma of the uterine cervix, 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 contain 17 types, including 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82, and other unclassified oncogenic genotypes 6 and 11. 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 HPV16 and HPV18 is more common, and HPV16 in particular is more 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 on high-risk types have shown that among the low-risk HPV types, HPV6 and HPV11 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 scenarios: a high risk of pre-existing CIN and cervical cancer, and 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 of HPV carcinogenesis and cervical cancer susceptibility Studies at home and abroad almost unanimously agree that HPV infection is not necessarily carcinogenic, and it takes 5-10 years from HPV infection to cervical cancer production, during which the body’s immunity is enhanced and the virus can regress in 80% of infected patients on its own, especially in young women, and the risk of disease is mainly dependent on the specific subtypes of HPV, and during this process A series of transitions can occur, and it can be said that cervical cancer is a common infection with few adverse outcomes. 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, and once HPV has entered the basal cells, the viral capsid loosens 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. HPV- DNA content increases with the severity of cervical lesions, and the risk of carcinogenesis increases with the increase of viral load. (3) 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 implementation of secondary prevention of cervical cancer. There are three available detection methods, the traditional Pap Smear method, which has been significantly reduced in application and is still used in some economically less developed areas, and the liquid-based cytology test (ThinPrep pap test), which has been developed in the past 10 years or so. However, the subjective test cannot avoid the influence of subjective human factors, which limits its development and promotion. The value of HR-HPV clinical typing test, which is 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 low human factors, and 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-DNA HC2 testing in combination with liquid-based cytology for primary screening of cervical cancer in women over 30 years of age. 2012, the American Cancer Society ASC, the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) recommended HPV-DNA HC2 testing for primary screening of cervical cancer in women aged 30 to 65 years. In April 2014, the FDA adopted the first application of HPV testing alone to screen for cervical cancer in women over 25 years of age, an approach that could directly impact the prevalence of cytology in cervical cancer screening, highlighting the importance of high-risk HPV testing in cervical cancer screening. There are two main HR-HPV testing methods commonly used in China at this stage, one is the more mature hybridization capture (HC2) for HR-HPV DNA quantification, and the other is HPV typing by gene chip technology using a combination of polymerase chain reaction (PCR) and reverse dot hybridization (RDB). Since both can provide different information about HPV infection in the reproductive tract, they are widely used in screening and follow-up of cervical disease. 1. HC2 test: 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-HPV DNA HC2 and cytology have shown a higher rate of 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 so that the target molecules across the low-density gene chip membrane that has been fixed nucleic acid probes, rapid hybridization. It can simultaneously detect 23 subtypes of HPV-DNA, including 18 high-risk subtypes: 16, 18, 31, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 83, MM4. 5 low-risk subtypes: 6, 11, 42, 43, 44. (D) HPV infection high-risk factors Studies have shown that the distribution of HPV subtypes is influenced by several factors. The distribution of HPV subtypes is influenced by several factors and varies among 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 status, income, contraceptive method, number of pregnancies, mode of delivery, number of births, and other infections in the combined reproductive tract may be associated with HPV infection. In recent years, the focus of HPV research has shifted 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 infections.