There have been recent, significant changes in strategies and policies for elimination of cervical cancer and advances in research of human papillomavirus (HPV)-related diseases and their prevention and control. Based on the latest national and international research, and building on a consensus published in 2019, we developed an expert consensus on immunoprophylaxis of cervical cancer and other human papillomavirus-related diseases (2025 edition) in order to provide clinicians, disease prevention and control professionals, and vaccination staff a reference for the prevention and control of cervical cancer and other HPV-related diseases and systematic, comprehensive evidence-based support for the scientific use of HPV vaccines to optimize their prevention effectiveness.
Humans ; Uterine Cervical Neoplasms/virology* ; Papillomavirus Vaccines/therapeutic use* ; Papillomavirus Infections/prevention & control* ; Female ; Consensus ; Papillomaviridae/immunology* ; Vaccination ; Human Papillomavirus Viruses

Persistent infection with high-risk human papillomavirus(HR-HPV) is the primary etiological factor in cervical lesions and cervical cancer. Toll-like receptors(TLRs), as important pattern recognition receptors of the innate immune system, play a key role in the persistence of cervical HR-HPV infection. The "latent pathogen theory" in traditional Chinese medicine(TCM) holds that latent pathogens have both "latent" and "triggered" characteristics, which closely resemble the persistent infection and latent pathogenic potential of cervical HR-HPV. Guided by the "latent pathogen theory" and using contemporary immunological techniques, this paper explores the bidirectional immunomodulatory effects of TLRs in the persistence of cervical HR-HPV infection and their relationship with latent pathogens. The results indicate that TLRs play a crucial role in immune recognition and modulation. Dysregulation and overactivation of TLRs can induce chronic inflammation, allowing cervical HR-HPV to persist and evade immune detection. TLR dysfunction, coupled with a deficiency in healthy Qi that prevents the expulsion of pathogens, is a critical factor in the pathogenicity of latent pathogens. Restoring healthy Qi to modulate the immune functions of TLRs emerges as an important strategy for clearing cervical HR-HPV infection. By harmonizing the spleen and kidney and regulating immune balance, it is possible to reverse cervical HR-HPV infection, providing a scientific basis for clinical research.
Humans ; Toll-Like Receptors/genetics* ; Female ; Papillomavirus Infections/genetics* ; Papillomaviridae/immunology* ; Persistent Infection/genetics* ; Uterine Cervical Neoplasms/immunology* ; Animals ; Medicine, Chinese Traditional ; Cervix Uteri/immunology* ; Human Papillomavirus Viruses

We aim to study the semen carriage of human papillomavirus (HPV) and evaluate its association with patient characteristics. We conduct a single-center cohort study at Amiens University Hospital Center (Amiens, France). From May 1 to October 31, 2021, 461 men consulting for infertility and with semen analysis data were included. Each participant gave his written informed consent for the use of laboratory, demographic, clinical, and lifestyle data. A proportion of the semen samples were sent to a virology laboratory for HPV screening in a polymerase chain reaction (PCR) assay. In univariate and multivariate analyses with a logistic regression model, HPV + and HPV - groups were compared with regard to semen characteristics (including the DNA fragmentation index and the sperm decondensation index) and demographic, clinical, and lifestyle variables. Semen HPV carriage was detected in 22.3% of the patients. High-oncogenic-risk HPV genotypes were predominant (57.6%). Multivariate analysis showed that HPV carriage was significantly associated with the presence of at least one abnormal spermogram dinging (according to the 6 th World Health Organization criteria), with an adjusted odds ratio (OR) of 4.10 (95% confidence interval [CI]: 2.32-7.25, P < 0.001). A statistically significant association was also found for the type of infertility (OR: 1.61, 95% CI: 1.00-2.57, P = 0.05), the presence of varicocele (OR: 3.99, 95% CI: 1.48-10.71, P = 0.01), and a history of cryptorchidism, testicular ectopia, or monorchidism (OR: 3.54, 95% CI: 1.07-11.66, P = 0.04). Infection with a single HPV genotype or multiple HPV genotypes was significantly associated with at least one abnormal spermogram finding for all HPV oncogenic risk groups (OR: 3.93, 95% CI: 2.08-7.41, P < 0.001; and OR: 4.11, 95% CI: 1.58-10.68, P = 0.01, respectively). The association between sperm HPV carriage and the risk of infertility was statistically significant in a multivariate analysis (OR: 5.63, 95% CI: 3.16-10.01, P < 0.001) and after adjustment for the propensity score (OR: 6.10, 95% CI: 3.33-11.21, P < 0.001). Our results suggest that semen HPV carriage has an impact on male fertility. Sperm screening for HPV might be a useful addition to the work-up for male infertility.
Humans ; Male ; Adult ; Infertility, Male/epidemiology* ; Papillomavirus Infections/complications* ; Semen/virology* ; Semen Analysis ; Prevalence ; Papillomaviridae/genetics* ; Cohort Studies ; Spermatozoa/virology* ; Middle Aged ; France/epidemiology* ; Human Papillomavirus Viruses

Human papilloma virus (HPV), a cancer-causing DNA virus, is a most common sexually transmitted virus and one of the major public health problems worldwide currently. Although HPV infection is relatively common in men, routine HPV detection is still difficult to be applied in clinical practice due to the lack of standard HPV detection methods and the complexity of its detection. Recent studies have explored the relationship between HPV and genitourinary tumors, revealed different results because of geographic differences, histological subtypes and detection methods, and stressed the importance of clarifying the role of HPV in the development and progression of genitourinary tumors. This review focuses on the complicated relationship of HPV with male genitourinary tumors, reveals its main carcinogenic mechanisms, and presents a new insight into the impact of HPV on the genitourinary system.
Humans ; Male ; Papillomavirus Infections/virology* ; Papillomaviridae ; Urologic Neoplasms/virology*

Female ; Humans ; Adenocarcinoma in Situ ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections ; Cervix Uteri/pathology* ; Adenocarcinoma/pathology* ; Papillomaviridae ; DNA, Viral

The study employed network Meta-analysis to evaluate the efficacy and safety of Chinese patent medicines combined with recombinant human interferon α-2b(interferon) in the treatment of cervical human papillomavirus(HPV) infections. The relevant randomized controlled trial(RCT) published from inception to May 8, 2024 were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science. The modified Jadad scale and the Cochrane risk of bias tool were used to evaluate the quality of the included studies, and RevMan 5.4, R 4.3.3, and Stata 17 were used for data analysis. A total of 105 RCTs were included, involving 12 732 participants and 7 Chinese patent medicines: Baofukang Suppository, Compound Seabuckthorn Seed Oil Suppository, Huangqi Shengmai Decoction, Kangfu Gel, Kangfuyan Capsules, Kushen Gel, and Puling Penyankang Granules. Network Meta-analysis yielded the following results:(1)For improving the negative conversion rate of HPV, SUCRA top-ranked intervention was Puling Penyankang Granules + interferon.(2) For shortening vaginal discharge time, SUCRA top-ranked intervention was Compound Seabuckthorn Seed Oil Suppository + interferon.(3) For reducing the serum level of hypersensitive C-reactive protein(hs-CRP), SUCRA top-ranked intervention was Baofukang Suppository + interferon.(4) For elevating the serum level of CD~+_4 T cells, SUCRA top-ranked intervention was Baofukang Suppository + interferon.(5) For elevating the serum level of CD~+_8 T cells, SUCRA top-ranked intervention was Kangfuyan Capsules + interferon.(6) For improving the CD~+_4/CD~+_8 ratio, SUCRA top-ranked intervention was Compound Seabuckthorn Seed Oil Suppository + interferon.(7)In terms of reducing serum tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), recurrence rate at 6 months after treatment, and incidence of adverse events, there were no significant differences between the interventions when compared pairwise. The cluster analysis revealed that Puling Penyankang Granules + interferon, Baofukang Suppository + interferon, Kangfu Gel + interferon, and Huangqi Shengmai Decoction + interferon simultaneously improved the negative conversion rate of HPV and reduced the incidence of adverse events. The findings suggested that Chinese patent medicines combined with interferon were effective in treating cervical HPV infection by enhancing the negative conversion rate, shortening the vaginal discharge time, and improving the levels of hs-CRP and T lymphocyte subsets. However, due to the limitations of sample size and quality of the included studies, these conclusions require further validation by studies with larger sample sizes and higher quality.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Papillomavirus Infections/virology* ; Interferon alpha-2/administration & dosage* ; Recombinant Proteins ; Drug Therapy, Combination ; Randomized Controlled Trials as Topic ; Antiviral Agents/administration & dosage* ; Interferon-alpha ; Papillomaviridae/physiology*

This study aims to establish a time-resolved fluorescence immunochromatography method for simultaneous determination of human papillomavirus (HPV) type 16 E6 and L1 protein concentrations. The amount of lanthanide microsphere-labeled antibodies, the concentration of coated antibodies, and the reaction time were optimized, and then a test strip for the simultaneous determination of the protein concentrations was prepared. The performance of the detection method was evaluated based on the concordance of the results from clinical practice. The optimal conditions were 8 μg and 10 μg of HPV16 L1 and E6-labeled antibodies, respectively, 1.5 mg/mL coated antibodies, and reaction for 10 min. The detection with the established method for L1 and E6 proteins showed the linear ranges of 5-320 ng/mL and 2-64 ng/mL and the lowest limits of detection of 1.78 ng/mL and 1.09 ng/mL, respectively. There was no cross reaction with human immunodeficiency virus (HIV), treponema pallidum (TP), or HPV18 E6 and L1 proteins. The average recovery rate of the established method was between 97% and 107%. The test strip prepared in this study showed the sensitivity, specificity, and diagnostic accuracy of 97.46%, 90.57%, and 95.32%, respectively, in distinguishing patients with cervical cancer and precancerous lesions from healthy subjects, with the area under the curve (AUC) of 0.980 1 and 95% Confidence Interval (CI) of 0.956 5 to 1.000 0. The time-resolved fluorescence immunochromatography combined with the test strips prepared in this study showed high sensitivity, high accuracy, simple operation, and rapid reaction in the quantitation of HPV16 E6 and L1 proteins. It thus can be used as an auxiliary method for the diagnosis and early screening of cervical cancer and precancerous lesions and the assessment of disease course.
Oncogene Proteins, Viral/immunology* ; Humans ; Chromatography, Affinity/methods* ; Female ; Human papillomavirus 16 ; Repressor Proteins/immunology* ; Capsid Proteins/immunology* ; Papillomavirus Infections/diagnosis* ; Fluorescence ; Uterine Cervical Neoplasms/virology*

Objective: To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma (ECA), and their assessment of patient prognosis. Methods: A retrospective study of 54 patients with ECA in the Cancer Hospital, Chinese Academy of Medical Sciences from 2005-2010 were performed. The cases of ECA were classified into two categories, namely human papillomavirus-associated adenocarcinoma (HPVA) and non-human papillomavirus-associated adenocarcinoma (NHPVA), based on the 2018 international endocervical adenocarcinoma criteria and classification (IECC). To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients, we used whole tissue section PCR (WTS-PCR) and HPV E6/E7 mRNA in situ hybridization (ISH) techniques, respectively. Additionally, we performed Laser microdissection PCR (LCM-PCR) on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of markers to identify HPVA and NHPVA. Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients' prognoses. Results: Of the 54 patients with ECA, 30 were HPVA and 24 were NHPVA. A total of 96.7% (29/30) of HPVA patients were positive for HR-HPV DNA and 63.3% (19/30) for HR-HPV E6/E7 mRNA, and 33.3% (8/24) of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected (0/24), and the differences were statistically significant (P<0.001). LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative, which was in good agreement with the E6/E7 mRNA ISH assay (Kappa=0.842, P=0.001). Analysis of the ROC results showed that the AUC of HR-HPV DNA, HR-HPV E6/E7 mRNA, and p16 to identify HPVA and NHPVA were 0.817, 0.817, and 0.692, respectively, with sensitivities of 96.7%, 63.3%, and 80.0% and specificities of 66.7%, 100.0%, and 58.3%, respectively. HR-HPV DNA identified HPVA and NHPVA with higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR=19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR=14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions: HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative.
Female ; Humans ; Papillomavirus Infections/diagnosis* ; Retrospective Studies ; Uterine Cervical Neoplasms/pathology* ; Prognosis ; Oncogene Proteins, Viral/genetics* ; Human Papillomavirus Viruses ; Adenocarcinoma/pathology* ; RNA, Messenger/genetics* ; Papillomaviridae/genetics* ; RNA, Viral/genetics*

Objective: To investigate the natural regression and related factors of high-grade squamous intraepithelial lesion (HSIL) in the cervix of childbearing age women, and to evaluate the applicability of conservative management for future fertility needs. Methods: This study included 275 patients of reproductive age with fertility needs, who were diagnosed as HSIL by biopsy from April 30, 2015 to April 30, 2022, including 229 cases (83.3%) cervical intraepithelial neoplasia (CIN) Ⅱ and 46 cases (16.7%) CIN Ⅱ-Ⅲ. They were followed-up without immediate surgery in the First Affiliated Hospital of Nanjing Medical University. The median follow-up time was 12 months (range: 3-66 months). The regression, persistence and progression of lesions in patients with HSIL were analyzed during the follow-up period, the influencing factors related to regression and the time of regression were analyzed. Results: (1) Of the 275 HSIL patients, 213 cases (77.5%, 213/275) experienced regression of the lesion during the follow-up period. In 229 CIN Ⅱ patients, 180 cases (78.6%) regressed, 21 cases (9.2%) persisted, and 28 cases (12.2%) progressed. In 46 CIN Ⅱ-Ⅲ patients, 33 cases (71.7%) regressed, 12 cases (26.1%) persisted, and 1 case (2.2%) progressed to invasive squamous cell carcinoma stage Ⅰ a1. There was no significant difference in the regression rate between the two groups (χ²=1.03, P=0.309). (2) The average age at diagnosis, age <25 years old at diagnosis were independent influencing factor of HSIL regression in univariate analysis (all P<0.05). There was no significant difference between HSIL regression and pathological grading, the severity of screening results, human papillomavirus (HPV) genotype, colposcopy image characteristics, number of biopsies during follow-up and pregnancy experience (all P>0.05). (3) The median regression times for patients aged ≥25 years and <25 years at diagnosis were 15 and 12 months, respectively. Kaplan-Meier analysis showed that age ≥25 years at diagnosis significantly increased the median regression time compared to <25 years (χ²=6.02, P=0.014). Conclusions: For HSIL patients of childbearing age, conservative management without immediate surgical intervention is preferred if CINⅡ is fully evaluated through colposcopy examination. Age ≥25 years at diagnosis is a risk factor affecting the prognosis of HSIL patients.
Pregnancy ; Humans ; Female ; Adult ; Cervix Uteri/pathology* ; Uterine Cervical Neoplasms/pathology* ; Uterine Cervical Dysplasia/pathology* ; Biopsy ; Colposcopy/methods* ; Squamous Intraepithelial Lesions/pathology* ; Carcinoma in Situ/pathology* ; Papillomaviridae/genetics* ; Papillomavirus Infections/diagnosis* ; Squamous Intraepithelial Lesions of the Cervix/pathology*

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ²=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ²=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.
Female ; Humans ; Adult ; Middle Aged ; Cervix Uteri/pathology* ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections/diagnosis* ; Cell Wall Skeleton ; Persistent Infection ; Powders ; Uterine Cervical Dysplasia/pathology* ; Immunotherapy ; Papillomaviridae