UNASSIGNED: Persistent human papillomavirus (HPV) infection remains a key risk factor for cervical cancer. HPV-based primary screening is widely recommended in clinical guidelines, and further longitudinal studies are needed to optimize strategies for detecting high-grade cervical lesions compared to cytology.
UNASSIGNED: From November 2015 to December 2023, 31,942 participants were included in the real-world observational study. Among those, 4,219 participants underwent at least two rounds of HPV tests, and 397 completed three rounds of HPV tests. All participants were tested for high-risk types of HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68 (hrHPV) and low-risk types of HPV6/11 genotyping. Some participants also received cytology or colposcopy with pathology.
UNASSIGNED: In the cross-sectional cohort, the prevalence of hrHPV and all HPV subtypes was 6.6% (2,108/31,942) and 6.8% (2,177/31,942), respectively. The three top hrHPV genotypes were HPV52 (1.9%), HPV58 (0.9%), and HPV16 (0.9%). Age distributions showed two peaks at 45-49 and 60-65 years. For the primary screening cohort, the hrHPV prevalence rate increased from 4.8% in 2015-2017 to 7.0% in 2020-2020 and finally reached 7.2% in 2023. For the longitudinal cohort study, the hrHPV prevalence rates in the repeated population (3.9, 5.3, and 6.0%) were lower than the primary hrHPV screening rates (6.6%), which indicated that repeated screening might decrease the prevalence rate. Methodologically, the hrHPV (89.5%) and the screening group of 16 subtypes (92.3%) demonstrated superior sensitivity than the cytology group (54.4%). Moreover, the longitudinal study indicated that the persistent hrHPV subgroup had a significantly higher (p = 0.04) incidence of high-grade squamous intraepithelial lesions and more histology progression events (7/17 vs. 0/5) than the reinfection group.
UNASSIGNED: The study indicates a rising high-risk HPV prevalence in Dongguan, with repeated screening reducing this trend. The findings support HPV-based primary screening and might guide HPV vaccination and cervical cancer prevention in South China.

Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women.
A total of 3251 hrHPV-positive women aged 30-82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated.
CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 -) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%).
PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals.
ChiCTR2100048972. Registered on 19 July 2021.

OBJECTIVE: Low-grade squamous intraepithelial lesion (LSIL) is one of two categories of cervical intraepithelial lesions. Given that controversy exists regarding its management, this comparative study aimed to evaluate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating LSIL of the high-risk human papillomavirus (HR-HPV)-infected cervix.
METHODS: A total of 218 patients (25-45 years old) with cervical LSIL associated with HR-HPV who underwent ALA-PDT, loop electrosurgical excision procedure (LEEP), or observation only were included. The clearance rates of cervical LSIL and HR-HPV between the ALA-PDT, LEEP, and observation groups were compared at 6 and 12 months follow-up. Adverse reactions were also compared. The factors affecting the clearance on ALA-PDT of cervical LSIL were evaluated.
RESULTS: There were no statistically significant differences in lesion and HR-HPV clearance rates between the ALA-PDT and LEEP groups at 6 and 12 months. However, the lesion and HR-HPV clearance rates were significantly higher in the ALA-PDT group than that in the observation group. The adverse reaction rate was significantly lower in the ALA-PDT group than in the LEEP group.
CONCLUSIONS: For patients with cervical LSIL, the lesion and HR-HPV clearance rates after ALA-PDT were close to those after LEEP and significantly higher than in the observation group. Moreover, the adverse reaction rate for ALA-PDT was much lower than that for LEEP. Therefore, ALA-PDT provides a new option for the minimally invasive treatment of cervical LSIL.

Objective: To investigate the triaging efficacy of the human papillomavirus (HPV) 16/18 E7 oncoprotein assay for high-grade cervical intraepithelial neoplasia (CIN2+) screening in HPV 16/18-positive patients in a tertiary hospital in China. Methods: We collected 476 cervical cell samples from women who tested positive for HPV 16/18 in the gynecological clinic of Peking Union Medical College Hospital between September 2018 and September 2022 and analyzed them by the HPV 16/18 E7 oncoprotein assay before colposcopy and biopsy. The study assessed the triaging efficacy of the HPV 16/18 E7 oncoprotein assay in HPV 16/18-positive patients by analyzing its performance against the gold standard of histologically confirmed CIN2+. Results: The positive rate of the HPV 16/18 E7 oncoprotein assay was 41.0% (114/278) in the negative for intraepithelial lesions and malignancy/CIN1 group and 80.3% (159/198) in the CIN2+ group. For triage of women with a positive HPV 16/18 test for CIN2+ detection, the HPV 16/18 E7 oncoprotein assay had a sensitivity, specificity, positive predictive value, and negative predictive value of 80.3%, 59.4%, 58.5%, and 80.9%, respectively. Furthermore, longitudinal follow-up of five patients showed a good correlation between the expression of the HPV 16/18 E7 oncoprotein and cervical lesion grades. Conclusions: As a triage method for HPV 16/18-positive patients, the HPV 16/18 E7 oncoprotein assay improves the specificity, reduces the colposcopy referral rate, and has the potential for long-term monitoring of high-grade CIN.

Persistent high-risk human papillomavirus (hrHPV) infection is associated with most cervical cancers. This study aims to investigate the prevalence of and independent risk factors for hrHPV infection among women residing in rural areas of Shanxi Province, China.
Data from the records of the cervical cancer screening programs for rural women in Shanxi Province were retrospectively collected. Women receiving primary HPV screening between January 2014 and December 2019 were included. The detection rate of hrHPV was calculated, and the independent risk factors for hrHPV infection were analyzed by multivariate logistic regression.
Among the women included, the overall infection rate of hrHPV was 14.01% (15,605/111,353), with the top five subtypes being HPV16 (24.79%), HPV52 (14.04%), HPV58 (10.26%), HPV18 (7.25%), and HPV53 (5.00%). The independent risk factors for hrHPV infection were specific geographical regions, testing years, older age, lower education level, inadequate previous screening, bacterial vaginosis, trichomonas vaginitis, and cervical polyps.
Rural women over 40 years of age, especially those who had never received screening, have a significantly increased risk for hrHPV infection and should be the target population with priority in cervical cancer screening.

Although vaginal microbiota (VM) may interact with human papillomavirus (HPV) infection and clearance, longitudinal data remain very limited. We aimed to investigate the association between VM at baseline and the clearance of high-risk HPV (HR-HPV) infection within 12 months. Cervical swabs were collected at diagnosis from 85 patients with HR-HPV infection and histologically confirmed cervical lesions, including cervicitis, low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion. Microbiome analysis was performed using 16S rRNA gene sequencing. Among the 73 women included in the analyses, HPV clearance was observed in 58.9% of the patients within 12 months. No significant difference was observed between the HPV-cleared and HPV-uncleared groups regarding age, disease stage, HPV subtype, VM community state types, and VM diversity (α and β). Women with the depletion of enterococcus ASV_62 and enrichment in Lactobacillus iners at baseline were less likely to have HPV clearance at month 12. Further analysis revealed a significant negative association between high abundance of L. iners and HPV clearance in patients who received non-operative treatment (OR = 3.94, p = 0.041), but not in those who received operative treatment (OR = 1.86, p = 0.660). Our findings provide new evidence for the potential role of VM in the persistent HR-HPV infections.

UNASSIGNED: To assess the efficacy and safety of focused ultrasound (FU) for high-risk human papillomavirus (HR-HPV) infection-related cervical low-grade squamous intraepithelial lesions (LSIL).
UNASSIGNED: Of 185 patients who met the inclusion criteria for this prospective study from October 2020 to November 2021, 95 received FU and 90 were followed up only. At the six-month follow-up, the HR-HPV clearance and LSIL regression rates of the groups were compared and factors affecting HR-HPV clearance were analyzed. The safety and side effects of FU were evaluated.
UNASSIGNED: No significant difference was found in the baseline clinical data between the two groups (p > 0.05). At the six-month follow-up, the HR-HPV clearance rates were 75.6% in the FU group and 25.6% in the observation group (p = 0.000). The LSIL regression rates were 89.5% in the FU group and 56.4% in the observation group (p = 0.000). Multivariate logistic regression analysis showed that the HR-HPV clearance rate in the FU group was 9.03 times higher than that in the observation group (95% confidence interval [CI], 3.75-21.73, p = 0.000), and the clearance rate of single-type HR-HPV infections was 5.28 times higher than that of multi-type infections (95% CI, 1.83-15.23, p = 0.002). The mean intraoperative bleeding was 1.8 ± 0.6 (1-3) mL; the mean intraoperative pain score was 2.6 ± 1.0 (1-6).
UNASSIGNED: For patients with HR-HPV infection-related histological LSIL, FU can eliminate HR-HPV infection and cause lesions to regress in a short time, with few adverse effects and good tolerance.

UNASSIGNED: The Chinese government has taken action to prevent cervical cancer by implementing the National Cervical Cancer Screening Programme in Rural Areas (NACCSPRA), which was launched in 2009. Numerous studies have demonstrated that long-term cervical cancer screening alters human papillomavirus (HPV) infection rates and cervical disease detection. Nearly 80 million women have been screened over 10 years, representing <30% of the target population; however, in some rural areas, such as Ordos City of Inner Mongolia Autonomous Region, Xiangyuan County of Shanxi Province, and Jinyun County, and Jingning County of Zhejiang Province, programs for prevention and treatment of cervical cancer have been implemented. Numerous studies have demonstrated that long-term cervical cancer screening alters rates of human papillomavirus (HPV) infection and cervical disease detection. In this study, we aimed to determine the infection rates of high-risk HPV (hrHPV) and the detection rate of cervical lesions; and changes in factors associated with cervical cancer, to provide scientific data to inform efforts to eliminate cervical cancer in rural areas.
UNASSIGNED: This was a cross-sectional, population-based, and multi-center survey. Populations from three rural areas of China (Ordos City of Inner Mongolia Autonomous Region, Xiangyuan County of Shanxi Province, and Jinyun County and Jingning County of Zhejiang Province) were selected and 9,332 women aged 20-64 years old were invited to participate in cervical cancer screening by both cytology and HPV testing. The outcomes assessed were: infection rates with hrHPV, HPV16, 18, 16/18, and other 12 hrHPV types (HPV 31,33,35,39,45,51,52,56,58,59,66 and 68); detection rates of cytological and histological lesions; and factors associated with HPV infection.
UNASSIGNED: A total of 9,217 women aged 45.62 ± 8.02 years were included in this study. Infection rates with hrHPV, HPV 16, 18, 16/18, and other 12 hrHPV types were 16.3%, 3.0%, 1.5%, 4.3%, and 13.6%, respectively. There were significant differences among the age-specific HPV infection rates (P < 0.05). Infection rates with hrHPV, 16, 18, 16/18, and the other 12 hrHPV types showed a single peak infection mode, with a peak age of 56-65 years old. Age, marital status, number of live births, education level, reproductive disease history, and a history of alcohol consumption were risk factors for hrHPV infection. The detection rate of cytological abnormalities was 12.98% in the study and was higher in women older than 56 years old. The detection rates of cervical intraepithelial neoplasia CIN2+ and CIN3+ in the population were 1.45% and 0.77%, respectively. The highest incidence rates of CIN2+ and CIN3+ were 32.12% and 17.51%, respectively, in the 41-45 years old group.
UNASSIGNED: Infection rates with hrHPV, HPV16, and cervical lesions among our screening population were lower than the mean level in rural areas of China. Infection rates with hrHPV, HPV16, 18, and 16/18 showed a single-peak infection pattern, with the peak age of infection being 56-65 years old. Risk factors for hrHPV infection were age, history of alcohol consumption, marital status, reproductive diseases, education level, and the number of live births. Based on these data, we recommend that cervical cancer screening be offered to women older than 30 years in rural areas, particularly those aged 41-45 years.

High-risk human papillomavirus (hrHPV) infection has been associated with a higher probability of progression to cervical cancer. However, several extensive studies have reported that the presence of hrHPV can lead to a better prognosis, but the mechanism of how this occurs is unclear. In this study, microbiological analysis was used to identify HPV infection as a factor for the prognosis of patients with cervical squamous cell carcinoma (CSCC). Comparing the interactions of HPV+ and HPV- malignant cells with immune cells as well as the trajectory of malignant cells either with or without HPV, we found that most of the HPV+ cells are well differentiated while HPV- cells appear to be hypo-fractionated. Using transcriptomic and immunostaining data, we validated a set of unfavourable molecules in the HPV- CSCC cells, including KRT16, ITGB1, CXCR1, VEGFA, CRCT1 and TNFRSF10B/DR5. This study provides a basis for the development of a rational post-operative follow-up programme and the development of an appropriate treatment plan for patients with cervical cancer.

Mycoplasma genitalium (MG) and Chlamydia trachomatis (CT) are the most common sexually transmitted pathogens, which can cause cervicitis, pelvic inflammation and infertility in female. In the present study, we collected the basic information, clinical results of leucorrhoea and human papillomavirus (HPV) infection of patients, who were involved in both MG and CT RNA detection in West China Second Hospital of Sichuan University from January 2019 to April 2021, ranging from 18 to 50 years old. The results showed that the infection frequencies of MG and CT were 2.6% and 6.5%, respectively. The infection rate of CT in gynaecological patients was significantly higher than that of MG (P < 0.001). Moreover, patients with CT infection often had symptoms of gynaecological diseases, while patients with MG infection remain often asymptomatic. By exploring the connection between MG or CT infection and vaginal secretions, we found that the infection of MG or CT promoted to the increase of vaginal leukocytes, and CT infection exacerbated the decrease of the number of Lactobacillus in the vagina. Further analysis suggested that independent infection and co-infection of MG or CT resulted in abnormal vaginal secretion, affecting the stability of vaginal environment, which may induce vaginal diseases. Unexpectedly, our study found no association between MG or CT infection and high-risk HPV infection. In conclusion, our study explored the infection of MG and CT among women in Southwest China for the first time, and revealed that the infection of MG or CT would affect the homeostasis of vaginal environment, which laid a foundation for the clinical diagnosis and treatment of MG and CT infection.