Comparison Of HR-HPV Infection Prognosis Characteristics And Risk Prediction Between Women With Normal And Low Grade Cervical Intraepithelial Neoplasia

Objective:Persistent infection of high-risk human papillomavirus(HR-HPV)is the main etiological factor for cervical cancer and precancerous lesions.Women with normal cervix(NC)but abnormal cytology are at high risk for HR-HPV infection,while low-grade cervical intraepithelial neoplasia(CIN1)is an early stage of cervical precancerous lesions and can undergo bidirectional metastasis.Obviously,normal cervical(NC)and CIN1 women who are infected with HR-HPV have a risk of developing cervical cancer,but it is unclear what characteristic changes and major differences in the prognosis of HR-HPV infection are in these two populations.Therefore,it is important to identify the changes and prognosis characteristics of HR-HPV infection in NC women and CIN1 women in the early stages of cervical carcinogenesis,and to conduct risk prediction based on factors that affect the prognosis,in order to effectively prevent the occurrence and development of cervical carcinogenesis.This study conducted a two-year follow-up observation on NC and CIN1 women in the community married women cohort established by the research group in the early stage,with the aim of exploring the characteristics of HR-HPV infection and conducting risk prediction,in order to open up new ideas for in-depth research on HR-HPV infection and prevention and control of cervical cancer.Methods:In the community married women cohort established earlier by the research group,1503 women with pathologically confirmed cervical normal(NC)and 564 women with low grade cervical intraepithelial neoplasia(CIN1)were selected as the study subjects for a two-year follow-up observation.On the basis of collecting baseline data of all study subjects,HPV typing was performed on cervical exfoliated cells of the study subjects at baseline and within two years of follow-up using flow cytometry.The results of HPV testing between baseline and two years of follow-up were compared to determine the clearance of HR-HPV infection and the prognosis of HR-HPV persistent infection(homotypic persistent infection,heterotypic persistent infection,persistent single infection,persistent multiple infections).By analyzing the HR-HPV clearance rate and the persistent infection rate of HR-HPV in NC and CIN1 women during the entire follow-up period,the characteristics and differences of the prognosis of HR-HPV infection in NC and CIN1 women were revealed.SPSS 26.0software was used for statistical description and analysis.The software R 4.1.0 was used to construct a random survival forest model to explore important characteristic factors that affect the prognosis of HR-HPV infection,and the ROC curve was used to evaluate its value.A nomogram model was constructed to predict the risk of HR-HPV infection prognosis.The C-index and calibration curve were used to complete the detection and evaluation of the discrimination and calibration of the nomogram model.Statistical significance was set atα=0.05.Results:1.Analysis of HR-HPV infection: At baseline,the HR-HPV infection rate of 1 503 NC women was 24.0%,with the top five types of HPV16,52,58,53,and 51 in order of infection rate;The infection rate of HR-HPV among 564 CIN1 women was 28.4%,and the top five types of infection rate were HPV16,58,52,18,and 56.The prevalence of HR-HPV infection in NC women during the two year follow-up period was 18.4%,with the top five types of HPV16,58,52,39,and 18 in turn;The infection rate of HR-HPV in CIN1 women is 27.5%,and the top five types of infection rate are HPV16,58,52,53,and 39.2.HR-HPV infection prognosis analysis: Within two years of follow-up,the HR-HPV clearance rates for NC and CIN1 women were 67.8% and 51.1%,respectively,and the persistent infection rates were 32.2% and 56.4%,respectively.In both NC and CIN1 women,the clearance rate of HPV16 is the lowest,and the persistent infection rate is the highest.The clearance rate of HPV16 in NC women(5.7%)is higher than that in CIN1 women(4.5%),and the persistent infection rate of HPV16 in CIN1 women(13.5%)is higher than that in NC women(8.3%).Homotypic and single HR-HPV are more likely to develop persistent infection in NC and CIN1 women than heterotypic and multiple HR-HPV.3.Analysis of influencing factors on the prognosis of HR-HPV infection: In NC women,bathing frequency >1 time/week can reduce the risk of persistent HR-HPV infection,while age ≥50 years old,menstrual sex,and husband smoking can increase their risk.High school education and above can reduce the risk of persistent HR-HPV infection.Age ≥50 years can increase the risk of persistent HR-HPV infection.Contraception can increase the risk of persistent HR-HPV infection.Bathing frequency >1 time/week can reduce the risk of persistent single/multiple HR-HPV infection.Menstrual sex can increase the risk of persistent single HR-HPV infection.In CIN1 women,washing the vagina after sex and bathing >1 time/week can reduce the risk of persistent HR-HPV infection,while husband smoking and menopause can increase the risk.After sexual intercourse,vaginal washing can reduce the risk of persistent HR-HPV homotypic/heterotypic/single/multiple infections.The frequency of bathing >1 time/week can reduce the risk of persistent HR-HPV homotypic infection.Menopause can increase the risk of persistent HR-HPV homotypic/heterotypic/single/multiple infections.A history of gynecological surgery can increase the risk of persistent HR-HPV homotypic infection.Husband smoking can increase the risk of persistent HR-HPV single infection.4.Analysis of HR-HPV infection prognosis among different characteristic populations:Among NC women,age <50 years old,menopausal sex,husband non-smoking,bathing frequency >1 time/week,high school education or above,and non-contraceptives have higher HR-HPV clearance rates,while age ≥50 years old,menopausal sex,husband smoking,bathing frequency ≤1 time/week,junior high school education or below,and contraceptives have higher rates of persistent HR-HPV infection.Among CIN1 women,the clearance rate of HR-HPV was higher among those who had undergone vaginal washing after sexual intercourse,had a husband who did not smoke,had not menopause,had a bathing frequency of >1 time/week,and had no history of gynecological surgery.The rate of persistent HRHPV infection was higher among those who had not undergone vaginal washing after sexual intercourse,had a husband who smoked,had menopause,had a bathing frequency of ≤1time/week,and had a history of gynecological surgery.5.Risk prediction of persistent infection of HR-HPV: The random survival forest model shows that the importance of factors affecting persistent infection of HR-HPV among NC women is in the following order: menstrual sex,husband smoking,age ≥50 years old,bathing frequency >1 time/week,contraception,and high school or higher education level;Among CIN1 women,the order was husband smoking,menopause,vaginal washing after sex,history of gynecological surgery,and frequency of bathing >1 time/week.ROC showed that the AUC of the random survival forest model for NC and CIN1 women was 0.684(95%CI: 0.545-0.822)and 0.767(95%CI: 0.644-0.890),respectively.A risk prediction model for persistent infection of HR-HPV in NC and CIN1 women was constructed using the nomogram.The C-index of the model was 0.661 and 0.703,respectively.The calibration curve of the model was close to the ideal curve,and the calibration degree was good.Conclusion:1.After two years of follow-up,the infection rate of HR-HPV in NC and CIN1 women decreased,and the infection rate of HR-HPV in NC women before and after follow-up was lower than that in CIN1 women.Both NC and CIN1 women had HPV16,52,and 58 common types before and after follow-up.The main types of HR-HPV infection among local women were proposed,providing a targeted reference basis for the prevention and treatment of HRHPV infection.2.NC women have a higher clearance rate and a lower persistence rate of HR-HPV infection compared to CIN1 women,and homotypic and single HR-HPV are more likely to develop persistent infection compared to heterotypic and multiple HR-HPV in NC and CIN1 women.HPV16 is the most difficult type to clear and most prone to persistent infection in both NC and CIN1 women.It is suggested that strengthening the detection of HPV subtypes in women,paying close attention to homotypic and single infected individuals with HR-HPV,and paying attention to women who have been infected with HPV16 can help timely detect and prevent persistent infection of HR-HPV,effectively preventing the occurrence of cervical cancer.3.Older age,passive smoking,and poor sexual lifestyle are common risk factors for persistent HR-HPV infection in NC and CIN1 women.Good hygiene habits can help reduce the risk of persistent HR-HPV infection in women.Strengthening cultural education and improving contraceptive measures among NC women,as well as paying close attention to menopausal women and women with a history of gynecological surgery among CIN1 women,can effectively reduce the risk of persistent HR-HPV infection.It is suggested that attention should be paid to the above high-risk groups,and timely follow-up should be conducted.At the same time,efforts should be made to popularize knowledge related to HRHPV infection and cervical cancer prevention,and women should be reminded and urged to develop healthy lifestyles and good hygiene habits.4.Using a random survival forest model,important factors that should be given priority attention to persistent HR-HPV infection in NC and CIN1 women were identified.A risk prediction model for persistent infection of HR-HPV was constructed using a nomogram,which visualized the risk of persistent infection of HR-HPV in NC and CIN1 women and had certain predictive power.It provides a refined reference for predicting the continuous changes in HR-HPV infection in women with different characteristics,as well as enriches the prediction content of HR-HPV infection changes in the entire population.