Efficacy Analysis of Paiteling in Treating Persistent High-Risk Human Papillomavirus after Cervical Cancer Surgery

Summary

This retrospective cohort study evaluates the clinical efficacy of Paiteling, a Traditional Chinese Medicine compound, compared to recombinant human interferon gel in treating persistent high-risk human papillomavirus (HR-HPV) infection following cervical cancer surgery.

Abstract

Persistent infection with high-risk human papillomavirus (HR-HPV) following cervical cancer surgery poses a significant risk for disease recurrence and progression to vaginal intraepithelial neoplasia. This retrospective cohort study evaluated the comparative efficacy of Paiteling, a Traditional Chinese Medicine compound, versus recombinant human interferon gel in treating persistent HR-HPV infection post-hysterectomy. Thirty-six patients with persistent HR-HPV positivity were allocated to either Paiteling (n = 17) or interferon (n = 19) treatment groups. Comprehensive assessment included HPV DNA load, ThinPrep cytologic test results, and colposcopic findings at baseline, 6-month, and 12-month follow-ups. At 6 months, the interferon group demonstrated significantly higher cure rates (68.4% vs 17.6%, ²= 7.646, p = 0.006). However, a remarkable reversal was observed at 12 months, with Paiteling achieving superior clearance rates (94.1% vs 63.2%, ²=4.976, p = 0.044). Multivariable analysis confirmed Paiteling treatment as a strong predictor of HPV clearance (adjusted OR = 9.52, 95% CI: 1.11–220.32, p = 0.039). Subgroup analysis revealed consistent treatment effects across all HPV genotypes. Adverse events were mild and self-limiting, with no significant differences between groups (29.4% vs 10.5%, p. = 0.226). This study demonstrates Paiteling’s superior long-term efficacy for persistent postoperative HR-HPV infection, characterized by a unique delayed-but-sustained response pattern. The multi-targeted mechanism, favorable safety profile, and sustained viral clearance support Paiteling’s potential as an effective therapeutic option in postoperative management, though validation through larger prospective trials is warranted.

Introduction

Cervical cancer remains a significant global health burden, with persistent infection by high-risk human papillomavirus (HR-HPV) established as its primary cause¹. While surgical intervention is a cornerstone treatment for early-stage disease, persistent or re-emergent HR-HPV infection post-surgery poses a serious risk for cancer recurrence and the development of vaginal intraepithelial neoplasia (VAIN)². The key to ensuring long-term surgical success and improving patient survival lies in the effective clearance of residual HPV. The clinical challenge is substantial; studies indicate that a significant proportion of patients, reported between 10% to 25%, may remain HR-HPV positive after conization or hysterectomy, placing them in a high-risk category for disease recurrence³. This persistence is often attributed to the presence of residual virus in the vaginal vault or multifocal field changes that are not completely eradicated by localized surgical excision. Current conventional strategies for managing persistent HPV, including laser and cryotherapy, are often limited by factors such as tissue trauma and variable efficacy⁴. Furthermore, immunomodulators like interferon, while widely used, can exhibit inconsistent long-term clearance rates, potentially due to the development of antiviral resistance or failure to fully restore local immune surveillance in the postoperative microenvironment⁵.  

Recent genomic studies underscore the importance of considering population-specific genetic backgrounds in disease management and therapeutic development. The Hmong people, an ethnic minority group primarily located in southern China and Southeast Asia, exhibit unique genetic lineages and adaptation histories as revealed by genome-wide analyses⁶, and specific genetic susceptibilities to infectious diseases within Hmong communities highlight how population genetics can influence health outcomes⁷. These findings align with broader efforts, such as the Chinese Pangenome Consortium, which aims to create inclusive genomic references by sequencing diverse ethnic groups, thereby addressing disparities in genomic medicine⁸. Simultaneously, educational research highlights the need to broaden participation in STEM among underrepresented groups, including Hmong students, to ensure diverse perspectives in scientific research and healthcare⁹. In this context, Traditional Chinese Medicine (TCM) has garnered attention as a valuable resource for new drug development, offering potential benefits such as fewer side effects and lower cost¹⁰. Paiteling, a compound TCM preparation containing ingredients like honeysuckle and Sophora flavescens., has been used clinically to treat HPV infections¹¹. Recent studies have additionally demonstrated the robust clinical efficacy of Paiteling versus recombinant human interferon gel in treating persistent HR-HPV infections¹². Its proposed mechanisms include promoting the shedding of virus-infected cervical epithelial cells and inducing apoptosis in cancerous cells through the inhibition of the E6/E7-PI3K/Akt signaling pathway¹³. The multi-targeted approach of Paiteling is particularly relevant given the complex pathogenesis of HPV persistence. Beyond its direct effects on viral oncogenes, emerging evidence suggests that its active components may also modulate the local tumor microenvironment, potentially inhibiting pro-inflammatory pathways that support viral replication¹⁴. For instance, the suppression of Topoisomerase IIα-mediated secretion of IL-6 and IL-8, key cytokines in viral persistence, represents a plausible complementary mechanism that warrants further investigation¹⁵. This multifaceted action may provide a therapeutic advantage over single-target modalities, especially in the context of postoperative residual disease, where multiple pathogenic pathways are often involved.  

While previous studies have reported its efficacy against condyloma acuminatum, its effectiveness specifically for persistent HR-HPV infection following cervical cancer surgery requires further robust clinical investigation. This evidence gap is critical to address, as the postoperative anatomical and immunological milieu differs significantly from the primary infection setting. The healing tissues, altered local vascularity, and potential for biofilm formation present a unique therapeutic challenge that may respond differently to topical agents. It was hypothesized that Paiteling’s multi-targeted mechanism provides superior long-term HR-HPV clearance compared to interferon by specifically addressing this unique postoperative microenvironment. Therefore, the objective of this study was to retrospectively analyze and compare the clinical efficacy of Paiteling against the conventional therapy of recombinant human interferon gel in eradicating persistent HR-HPV in post-surgical cervical cancer patients, aiming to provide a novel, conservative local therapy for this high-risk cohort.

Protocol

This retrospective cohort study was conducted at Shengjing Hospital of China Medical University and approved by the Institutional Medical Ethics Review Committee (2023PS846K). The research adhered to the principles of the Declaration of Helsinki, and written informed consent was obtained from all participants before study enrollment. The reagents and the equipment used are listed in the Table of Materials.

1. Patient selection

A total of 36 patients who underwent hysterectomy for cervical malignancy were enrolled based on predefined criteria. Inclusion criteria comprised: age 32–76 years; documented preoperative HR-HPV positivity; persistent HR-HPV positivity at the 6-month postoperative follow-up; and the absence of colposcopic or histopathological abnormalities. Exclusion criteria included: acute genital tract inflammation; renal or hepatic dysfunction; inability to comply with follow-up requirements; cardiopulmonary abnormalities; and detection of HSIL/LSIL.

2. Treatment procedure and dosing regimen

Patients allocated to the Paiteling treatment group received therapy administered in 7-day cycles, typically spanning 4–8 cycles. The therapeutic protocol involved three progressive stages tailored to lesion regression and visual inspection with acetic acid findings. In the first stage, healthcare professionals applied a local wet dressing with Paiteling solution for 15 min, three consecutive days per week, with sea buckthorn oil administered on intervening days to facilitate wound healing. This initial phase continued for 1–8 weeks until the complete resolution of visible lesions. The second stage involved the continuation of the application protocol for 3–6 weeks to consolidate therapeutic effects. Finally, the third maintenance stage involved dressings with a 2% diluted Paiteling solution applied for 10 min daily during the first month, transitioning to an every-other-day application for the subsequent 2 months. Conversely, patients in the interferon treatment group received recombinant human interferon gel administered via .a graduated vaginal applicator. The gel was applied to the cervical surface and cervical canal at a standardized dosage of 1 g per session every other day for a 3-month duration. Patients maintained recumbency for approximately 30 min post-application to optimize drug retention. For both treatment groups, follow-up evaluations were conducted three months post-treatment cessation.  

3. Efficacy evaluation and follow-up

The primary efficacy endpoint was HPV clearance at the 12-month follow-up, defined as a composite of HPV-DNA <1.0 pg/mL, normal cytological findings, and the absence of colposcopic abnormalities. HPV nucleic acid detection employed the second-generation hybrid capture methodology, enabling the genotyping of 14 high-risk HPV types. Analytical thresholds defined positivity at an HPV DNA content ≥1.0 pg/mL and negativity at <1.0 pg/mL, following standard specifications. ThinPrep cytologic test samples were collected using approved disposable cervical cell collection systems during non-menstrual intervals, with strict avoidance of vaginal medication preceding sampling. Cervical secretions were cleared using a saline wipe or cotton ball before specimen collection to minimize blood and mucus contamination. Cytological abnormalities were defined as findings of atypical squamous cells of undetermined significance or greater severity. Furthermore, patients with persistent HPV positivity underwent comprehensive colposcopic evaluation using standard equipment. The examination protocol included a systematic assessment of cervical coloration, vascular architecture, and tissue characteristics. Dynamic tissue responses were documented following acetic acid application, and iodine staining patterns were recorded (Figure 1).  

4. Statistical analysis

Data analysis utilized R software (version 4.5.1) with complementary packages including tidyverse, broom, survival, gtsummary, pROC, and logistf. Analytical approaches encompassed descriptive statistics, group comparisons using t-tests, Chi-square tests, or Fisher’s exact tests as appropriate, univariable and multivariable logistic regression, subgroup analysis employing Firth’s penalized likelihood method, and predictive modeling with ROC curve analysis. Statistical significance was established at p. < 0.05 (two-tailed). Due to the modest sample size, 95% confidence intervals for logistic regression models were estimated using the profile likelihood method, and corresponding p-values were derived from likelihood ratio tests.

Results

The final analytical cohort comprised 36 patients with persistent high-risk HPV infection following cervical cancer surgery, while baseline characteristics demonstrated general comparability between treatment groups (Table 1), a statistically significant age difference was noted (Interferon group: 56.0 ± 5.6 years vs. Paiteling group: 50.0 ± 5.0 years; p. = 0.005). As illustrated in Figure 2, participants were allocated to either Paiteling (n = 17) or interferon (n ...

Discussion

This study provides compelling evidence supporting the superior long-term efficacy of Paiteling compared to interferon in managing persistent HR-HPV infection following cervical cancer surgery. Paiteling is proposed as an effective, conservative local therapy specifically tailored for the unique postoperative microenvironment, an area that currently lacks standardized treatment guidelines. The findings reveal a remarkable temporal pattern: while interferon demonstrated better initial response rates at 6 months, Paiteling...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
5% Acetic Acid	Chemical reagent	Shenzhen Andoff High-Tech Co., Ltd.	Shenzhen
Disposable Cervical Sampling Brush	Medical device	Hangzhou Aipeng Medical Instruments Co., Ltd.	Hangzhou
High-Risk HPV Nucleic Acid Detection Kit	Diagnostic reagent	Chaozhou Hybribio Biochemistry Co., Ltd.	Chaozhou
Lugol's Iodine Solution	Chemical reagent	Shenzhen Andoff High-Tech Co., Ltd.	Shenzhen
Opto-electronic Colposcope	Laboratory equipment	Leica Microsystems	Wetzlar
Paiteling Solution	Herbal preparation	Beijing Paiteling Biotechnology Co., Ltd.	Beijing
R Software (version 4.5.1)	Statistical software	R Foundation for Statistical Computing	Vienna
Recombinant Human Interferon $\alpha$-2b Gel	Pharmaceutical preparation	Zhaoke Pharmaceutical Co., Ltd.	Hefei
Sea Buckthorn Oil	Herbal preparation	Shengjing Hospital Pharmacy	Shenyang
ThinPrep® System (JY-8000B)	Laboratory equipment	Beijing Beidou Xinghang Biotechnology Co., Ltd.	Beijing