Cervical intraepithelial neoplasia (CIN) is a precancerous lesion caused by persistent infection with high-risk human papillomavirus (HPV), closely linked to the progression to cervical cancer (1). CIN is classified into low-grade (LSIL or CIN I) and high-grade lesions (HSIL, encompassing CIN II and III) (2). Persistent infection with high-risk HPV subtypes such as HPV16 and 18 is a key risk factor for developing high-grade CIN and cervical cancer (2–4). Untreated high-grade CIN has a risk of progression to invasive cancer, with CIN II having a 18% progression rate and CIN III ranging from 22 to 40% within 30 years (3, 5, 6). Globally, the incidence of HSIL in reproductive-aged women continues to rise, reaching 498/100,000 in recent Chinese data (7). Given this risk, current WHO and ASCCP guidelines recommend surgical excision—most commonly cold knife conization (CKC), laser conization, or the loop electrosurgical excision procedure (LEEP)—as the standard treatment (8–10). Conization, depending on cone size, is also considered a fertility-sparing treatment, albeit with variable obstetric impact (10–12). Surgical interventions, though effective, come with risks such as bleeding, infection, and scarring (13), as well as potential complications like cervical insufficiency, stenosis, and preterm birth in women of reproductive age (14, 15). As fertility preservation becomes an increasing concern for women of reproductive age, there is a growing demand for conservative alternatives for high-grade CIN (14).

Non-surgical strategies—including photodynamic therapy, immunomodulatory agents, and Traditional Chinese Medicine (TCM)—are attracting interest for their potential to avoid cervical tissue loss (10, 16–18). Among TCM approaches, external therapies such as fumigation, rubbing, and soaking with plant-derived preparations have been reported to achieve local viral clearance without the tissue damage associated with surgery (16, 17). Paiteling, a pure TCM formulation, has shown encouraging results in treating HPV infection and condyloma acuminatum (17, 19–21), yet its role in managing high-grade CIN remains unexplored. Here, we present a retrospective review of two cases of reproductive-age women with biopsy-confirmed HSIL and concomitant vaginal and cervical condyloma acuminatum, successfully managed with topical Paiteling.

High-grade cervical intraepithelial neoplasia (CIN II–III, HSIL) carries a low likelihood of spontaneous regression and a lifetime risk of progression to invasive cancer of 22%–40% (3, 5, 6). Accordingly, both the WHO and ASCCP recommend excisional treatment as the gold standard (8, 9). Nevertheless, excisional procedures may be followed by persistent high-risk human papillomavirus (hr-HPV) infection in up to 68% of patients, with ongoing viral persistence markedly increasing recurrence risk (4, 23). Furthermore, meta-analyses have demonstrated that prior excision is associated with significantly elevated risks of adverse obstetric outcomes, including a 1.78–3.78-fold increase in preterm birth, a 1.99-fold increase in premature rupture of membranes, and a 1.94-fold increase in low birth weight infants compared with women without prior excision (11, 14, 24).

Medical and other non-excisional approaches, such as topical immunomodulators (e.g., imiquimod), photodynamic therapy, and Traditional Chinese Medicine formulations, may avoid cervical tissue loss and thus potentially mitigate these obstetric risks (10, 16–18). Topical imiquimod and photodynamic therapy, which have shown lesion regression rates of 50%–80% in selected patients (25, 26). The APL-1702 (a photodynamic therapy drug-device combination) phase III trial also reported favorable HPV clearance and safety outcomes in a large HSIL cohort (27). Emerging robotic-assisted precision excision techniques also aim to minimize tissue removal while ensuring complete lesion eradication, aligning with the principles of non-excisional therapies that prioritize fertility preservation and reduction of obstetric complications (28, 29). In addition, adjuvant HPV vaccination has been shown to significantly lower the recurrence of high-grade CIN, with odds ratios of 0.33 for CIN II + and 0.28 for CIN III, underscoring its potential role in secondary prevention (30). Compared with these modalities, Paiteling represents a non-invasive, cost-effective alternative with potential antiviral and immunomodulatory effects, and without the need for specialized equipment. Our report suggests that Paiteling may offer comparable histological and virological remission, with minimal systemic adverse effects. However, the oncologic safety of non-excisional strategies remains less well established, with limited high-quality evidence on long-term recurrence rates, particularly in HSIL. Therefore, both oncologic safety and obstetric outcomes must be weighed when comparing medical and excisional approaches. Treatment selection should be individualized, balancing reproductive goals against the need to minimize cancer progression risk, ideally within the framework of shared decision-making and close post-treatment surveillance.

Paiteling, a topical formula developed by the Chinese Academy of Medical Sciences, combines Brucea javanica, Isatis tinctoria, Hedyotis diffusa, Sophora flavescens, and Cnidium monnieri (20, 21) (Supplementary Table 2). The alkaloids, flavonoids and quassinoids in these herbs synergistically lyse infected epithelial cells; shed necrotic debris removes latent HPV, while sea-buckthorn oil constituents (anthocyanins, quercetin) dampen inflammation and support re-epithelialisation (31). Paiteling down-regulates E6/E7 transcription, blocks PI3K/Akt signaling, and triggers apoptosis in cervical cancer lines (21, 32).

Clinical evidence—although limited to low-grade disease—has been encouraging. Cure rates of 92%–100% for condyloma acuminatum and 89% for LSIL have been reported, with minimal pain and no scarring (17, 19–21, 33). Our two HSIL cases extend these findings: topical Paiteling cleared hr-HPV and achieved durable histological remission without compromising cervical architecture. To the best of our knowledge, this is the first report on the use of Paiteling in biopsy-confirmed HSIL coexisting with genital warts. These preliminary observations are encouraging but warrant cautious interpretation. The study is inherently constrained by its retrospective nature, two-case sample size, single-center setting, absence of a comparator group, and relatively limited follow-up duration, which together limit the generalizability of the findings. Obstetric outcomes were not evaluated, and any conclusions regarding safety remain provisional. The evaluation of lesion regression in this report relied on histopathological clearance and HPV negativity. Future studies should incorporate standardized, validated outcome scoring systems for treatment response—such as the Lower Anogenital Squamous Terminology (LAST) criteria or immunologic markers to enhance objectivity and clinical translatability. Given the 12- to 16-month follow-up, our study cannot determine long-term recurrence or progression risk, particularly as latent HPV reactivation may occur beyond the follow-up horizon. Accordingly, our findings should be interpreted as preliminary, and long-term surveillance is essential for drawing definitive conclusions about sustained remission. No systemic side effects were reported in our cases; however, detailed safety data, particularly regarding systemic absorption, endocrine disruption, or reproductive toxicity of Paiteling, are lacking. Preclinical pharmacokinetic studies and reproductive toxicity models are warranted before wider clinical adoption, particularly in women seeking future pregnancies. Rigorous, randomized controlled trials incorporating virological endpoints and long-term obstetric follow-up are required to establish the efficacy, optimal regimen, and safety profile of this approach in reproductive-age women who decline or are ineligible for excisional therapy. Furthermore, optimal management of CIN should be grounded in comprehensive patient counseling, formal documentation of informed consent, and ethics committee oversight, ensuring that patients are fully apprised of the potential risks and benefits of all therapeutic options, and that autonomy is upheld throughout the decision-making process.

Topical Paiteling may be a promissing non-excisional option for selected women with HSIL who prioritize fertility preservation. Rigorous clinical trials are required to establish efficacy, safety, and obstetric impact.