Cervical cancer is a common malignancy in women. In developing countries, it is the first factor in female cancer mortality. In developed countries, the mortality rate has also been on the rise in recent years⋯. Cervical intraepithelial neoplasia (CIN) is a precancerous lesion that is closely related to cervical cancer. The evolution from cervical precancerous lesions to cancer is usually about 10 years. In recent years, a large number of epidemiological and molecular biological studies have shown that. Human papillomavirus (HPv) infection is one of the main causes of cervical cancer and precancerous lesions. Chen Ming, Department of Gynecology, General Hospital of Jinan Military Region
1. HPV structure and typing In 1974, Zur Hausen first proposed that HPV infection was closely related to cervical cancer. The HPV positivity rate in cervical cancer was reported to be as high as 99%. Currently, more than 100 HPV subtypes have been identified. A total of 27 species can be found in cervical cancer tissues [HPV belongs to the family Polyviridae, and is a cyclic diphasic DNA virus. The E6 and E7 transcriptional subunits are the oncogenes of the virus and encode the E6 and E7 proteins, which play a key role in viral replication. The oncogenic effect of the E6 protein is mainly through binding to the oncogene P53, which leads to inactivation of the P53 protein and promotes its degradation in the cell, thereby disrupting the detection point of the cell proliferation cycle. Ultimately, this leads to the proliferation cycle of cells infected with oncogenic HPV to continue to proliferate without the control of cell cycle detection sites. HPV cannot be cultured in animals due to the specificity of cervical epithelial cells that no longer divide, so the type cannot be determined by isolating the virus. Most HPV DNA is cloned directly from living tissue rather than from purified viral particles. And HPV has a narrow host cell spectrum, growing only in terminally differentiated skin or mucosal epithelial cells. HPV can be classified into cutaneous and mucosal classes based on their tissue heterophilicity. Within the mucosal category, they are further divided into low-risk and high-risk types based on their association with cervical cancer. The pathogenicity of different subtypes of HPV to cervical epithelium varies, with HPV.16, 18, 31, 33, 35 and 45 being high-risk types associated with high-grade CIN and cervical cancer, and HPV.6, 11, 34, 42, 43 and 44 being low-risk types associated with low-grade CIN and genital warts. The majority of the current literature reports that CIN I is mainly associated with HPV.6, 11, 31 and 35, while CIN 1I and CINIII are mainly associated with HPV.16, 18 and 33. The most common HPV types in cervical cancer are HPV-16 and 18.
2 .HPV infection and cervical precancer and cancer have been reported in studies. Less than 4% of normal women are infected with HPV. The detection rates in patients with CIN grade I, II and III are 30%, 55% and 65% respectively, while in cervical cancer the infection rate is basically 100%, indicating that the higher the CIN grade, the higher the HPV infection rate. In a survey of 8,000 women and a study of HPV DNA testing, it was found that 28% of the HPV DNA positive group developed CIN 1I or CINIII within 2 years, while only 3% of the negative group developed CIN I or CIN 1. Koutsky’s prospective study of women who were initially cytologically negative for HPV infection found that 28% of women who later presented positive for HPV infection developed CIN within 2 years, compared with 3% of women who were consistently negative for HPV infection. This suggests that after high-risk HPV infection, high-grade CIN can develop from low-grade CIN or from lesion-free epithelium in a relatively short period of time, and that high-risk HPV infection is an important factor contributing to the development or progression of CIN. On the other hand, some scholars have analyzed the cervical smears of 11,088 randomly obtained women and performed HPV DNA analysis on the cervical biopsies of 199 of them who developed CIN (120 of them were CIN grade I and 79 were CIN grade 1I and III) and found that 61% of CIN grade I had HPV infection and 74% of CIN grade 1I and III had HPV infection. Reproductive tract infection with high-risk HPV was the main factor for the high incidence of cervical cancer and CIN in local women. 100% of cervical cancer patients were positive for high-risk HPV infection, and about 97% of CIN grade II and CIN grade llI were positive. The rate of positivity in CIN grade I also reached 61.4%. It is generally believed that HPV DNA exists mainly in free form in benign lesions. A prospective study by Dalstein et al. showed that women with recurrent HPV infection have an increased risk of developing CIN grade II and III. A prospective study by Dalstein et al. showed that women with recurrent HPV infection had an increased risk of developing CIN grade II and III. None of the women with persistent HPV-negative or transient HPV infection progressed to CIN grade II or III during the follow-up. It is believed that persistent HPV infection plays an important role in the development of cervical lesions. It suggests that when HPV multiplication stops at a certain phase of the replication cycle, this persistent or recurrent HPV (especially high-risk types) infection may lead to cellular transformation to a malignant phenotype, which greatly increases the risk of developing cervical carcinoma in situ.
3 HPV infection and progression of cervical lesions Currently, whether HPV infection correlates with the occurrence and progression of cervical lesions is the focus of many studies. The relationship between HPV DNA levels measured by different methods and the progression of cervical lesions is still under debate. The results of some investigators show that. Moberg et al. concluded that high viral load increases the occurrence of HPV viral integration events and therefore, the risk of progression to invasive cancer increases with higher viral load. This may also be one of the reasons why viral load is also higher in those with high-grade lesions. However, it has also been reported in the literature that HPV DNA levels do not correlate with the progression of cervical lesions. The results of the study by Yeh Yun-Ying et al. showed that HPV DNA levels in patients with chronic cervicitis and CIN were measured. The difference in HPV DNA content between the two was not significant, i.e., there was no increasing trend in HPV DNA content as the degree of cervical lesions increased.
4 HPV infection outcome One study reported that the prevalence of HPV infection among 608 female college students was 43%. The average duration of HPV infection is 8 to 14 months, with more than 90% of cases resolving spontaneously within 2 years and less than 5% developing atypical hyperplasia of the cervix. In more than 90% of cases, the infection resolves within 2 years. About 1 percent of infected women develop external genital warts, and 5 percent or 10 percent develop CIN E. Since the vast majority of women with HPV infection do not develop malignancy, it is suggested that a single HPV infection may not be sufficient to cause cancer and that other factors should play an important role. Studies have suggested that the main factors affecting the regression of HPV infection include internal factors, the individual’s immune status, and external factors such as the subtype of HPV infection, duration of infection, and other factors such as smoking and sexual behavior of the male partner. After high-risk HPV infection. A large number of viruses keep replicating. The combination of self and external factors will eventually lead to cervical precancer and cancer. Therefore, it is especially important to strengthen the follow-up of HPV-infected women, relieve their mental fear, improve their own immunity and eliminate other high-risk factors, and monitor HPV and cervical exfoliation cell examination.