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Journal of Gynecologic Oncology logoLink to Journal of Gynecologic Oncology
. 2026 Apr 29;37(5):e98. doi: 10.3802/jgo.2026.37.e98

Chemotherapy plus camrelizumab for fertility preservation (NACI-F) in FIGO stage IB1 cervical cancer: a multicenter, single-arm, phase 2 trial

Yingjie Hu 1,2,*, Shuting Chen 1,2,*, Hanxu Cheng 1,2, Yingyan Han 1,2, Chaoyang Sun 1,2, Gang Chen 1,2, Jing Chen 1,2,†, Kezhen Li 1,2,†,✉
PMCID: PMC13655340  PMID: 42172490

Abstract

Background

The increasing prevalence of cervical cancer in younger women highlights the need for personalized fertility-preserving treatment strategies. Current fertility preservation approaches for early-stage cervical cancer primarily involve cervical conization and radical trachelectomy. However, removing part or all of the cervix can negatively impact reproductive outcomes. These procedures increase the risk of preterm birth and miscarriage, and sometimes require additional surgery due to positive margins. Combined chemotherapy and immune checkpoint inhibitor (ICI) therapy has demonstrated promising efficacy and tolerability in treating locally advanced cervical cancer. However, its role as a non-surgical, fertility-sparing treatment for stage IB1 disease remains unclear.

Methods

This multicenter, single-arm, phase II trial is designed to evaluate the efficacy and safety of combining chemotherapy with camrelizumab as a fertility-preserving strategy for patients with International Federation of Gynecology and Obstetrics 2018 stage IB1 cervical cancer. Key inclusion criteria include: 1) pathologically confirmed cervical squamous cell carcinoma, 2) transformation zone of TZ1 or TZ2, 3) programmed death-ligand 1 combined positive score ≥1, and 4) age 18–45 with a desire to preserve fertility. Key exclusion criteria include being unable to achieve pregnancy even with assisted reproductive technology; autoimmune disease requiring systemic therapy; and prior exposure to ICIs or contraindications to study drugs. A total of 40 patients will be recruited from multiple centers across China. Enrolled patients will receive 1 cycle of chemotherapy (nab-paclitaxel + cisplatin), 2 cycles of chemotherapy combined with camrelizumab, and 3 cycles of camrelizumab alone. Those who achieve tumors ≤2 cm, no new lesions, and a biopsy-proven pathological response will undergo cervical conization combined with pelvic lymphadenectomy or pelvic lymphadenectomy alone. The primary endpoint is the pathological complete response rate. Secondary endpoints include the negative human papillomavirus conversion rate, pregnancy rate, miscarriage rate, live birth rate, preterm birth rate, adverse events, quality of life, event-free survival, and overall survival.

Trial Registration

ClinicalTrials.gov Identifier: NCT06289062

Keywords: Uterine Cervical Neoplasms, Fertility Preservation, Immunotherapy, Conization, Combined Modality Therapy

INTRODUCTION

Cervical cancer is the fourth most common malignancy among women globally, with approximately 40% of patients of reproductive age [1]. According to data from the National Health Service (NHS) Cervical Screening Program in England, among patients with International Federation of Gynecology and Obstetrics (FIGO) staging data, approximately 90% of cases in women aged 20 to 29 were diagnosed at stage IB or earlier [2]. As fertility preservation becomes an increasingly important consideration, it is imperative to ensure oncologic safety while identifying appropriate fertility-sparing strategies for young women who strongly desire to conceive.

Cervical conization is a standard fertility-sparing treatment for stage IA disease, but the optimal approach for stage IB1 remains undefined. Current guidelines recommend stratified management based on individual risk factors, suggesting either cervical conization or radical trachelectomy (RT) [3,4]. Nevertheless, partial or complete cervical excision often adversely affects reproductive outcomes, rendering patients with “organs without function.” RT requires parametrial resection and is associated with severe surgical complications and impaired obstetric outcomes, including late miscarriage and preterm birth rates of 20%–57%, as well as increased incidences of cervical stenosis and uterine prolapse [5,6,7,8]. Although conization offers comparable oncologic safety and superior obstetric results in low-risk patients, residual lesions are detected in 21.4%–32.2% of specimens, often necessitating additional surgery [9,10]. Furthermore, the probability of preterm birth following conization remains 2.27 times greater than that in untreated colposcopy cohorts, with a concomitant preterm rate of 16.3% [11]. These limitations underscore the necessity for less invasive, fertility-preserving modalities.

Successful nonsurgical management models have emerged in other malignancies. For instance, oral high-dose progestin achieves pathological complete response (pCR) in over 80% of early endometrial cancer lesions, with live birth rates ranging from 69% to 82%, establishing endometrial cancer fertility preservation as a benchmark in gynecologic oncology [12]. In mismatch repair-deficient rectal cancer, a watch-and-wait strategy following neoadjuvant immunotherapy has enabled some patients to avoid radical surgery [13]. So, is it possible to achieve pCR with conservative therapy in cervical cancer, thereby reducing the need for surgery? Neoadjuvant chemotherapy (NACT) is currently a non-standard treatment option used before radical surgery in cases of locally advanced cervical cancer to reduce tumor size and improve surgical rate, while preserving ovarian function without radiation exposure. It is also employed as an adjunct therapy either before or after fertility-sparing surgery. However, NACT alone achieves limited efficacy, with pCR rates of 8.5% in stage IB3–IIA2 and only 26% in one small IB1 cohorts [14,15]. Such relative low rate of pCR is insufficient to achieve the objective of replacing surgery with chemotherapy alone and ensuring complete tumor eradication, underscoring more efficient therapeutic agents.

The remarkable efficacy of immunotherapy in solid tumors has led to the development of a novel neoadjuvant treatment paradigm that combines chemotherapy with immune checkpoint inhibitor (ICI) agents. This combination has significantly improved pCR rates across multiple solid tumor types. Camrelizumab, a programmed death receptor 1 (PD-1) inhibitor, is among these agents and has demonstrated efficacy in neoadjuvant regimens for non-small cell lung cancer [16], locally advanced esophageal squamous cell carcinoma [17], and locally advanced gastric or gastroesophageal junction adenocarcinoma [18]. Our team’s prior research has demonstrated that the incorporation of immunotherapy into NACT regimens (NACI trial) results in an increase in pCR rates, from 8.5% to 38%, among patients diagnosed with locally advanced cervical cancer [14,19]. These results suggest that chemoimmunotherapy has the potential to provide a higher pCR rate and non-surgical treatment alternatives for patients with early-stage disease.

Considering these factors, this study aims to evaluate the efficacy of chemoimmunotherapy in stage IB1 cervical cancer to enhance pCR rates and explore its potential as a non-surgical fertility-preserving therapeutic strategy.

MATERIALS AND METHODS

1. Objectives

To furnish the initial prospective evidence that endorses the utilization of chemoimmunotherapy as a treatment strategy that aims to preserve fertility in patients diagnosed with stage IB1 cervical cancer.

2. Trial design

The study is designed as a multicenter, single-arm, phase II trial evaluating the efficacy and safety of combining chemotherapy with camrelizumab as a fertility-preserving strategy for patients with programmed cell death ligand 1 (PD-L1) positive FIGO stage IB1 cervical squamous cell carcinoma. The trial is scheduled to be conducted across 15 tertiary hospitals in China. The primary analyses are scheduled to occur 4 months after the final patient completes treatment, with additional analyses to be conducted following the completion of both 3- and 5-year follow-up periods.

PD-L1 expression will be assessed at a central laboratory using the PD-L1 immunohistochemistry 22C3 pharmDx assay (Agilent Technologies, Santa Clara, CA, USA). Combined positive score (CPS) will be calculated as the number of PD-L1-positive cells (including tumor cells, lymphocytes, and macrophages) divided by the total number of tumor cells, multiplied by 100. Only patients with a CPS ≥1 will be eligible for enrollment. Enrolled patients will receive 1 cycle of priming chemotherapy (nab-paclitaxel plus cisplatin), followed by 2 cycles of combination chemoimmunotherapy (nab-paclitaxel, cisplatin, and camrelizumab), and then 3 cycles of immunotherapy (camrelizumab) (Fig. 1). Each treatment cycle is 21 days in duration. Detailed information regarding drug dosage and administration is provided in the “Treatment” section.

Fig. 1. Trial schema.

Fig. 1

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ASCCP, American Society for Colposcopy and Cervical Pathology; FIGO, International Federation of Gynecology and Obstetrics; HSIL, high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion; NCCN, National Comprehensive Cancer Network; SLN, sentinel lymph node.

*Repeat conization to obtain negative margins is acceptable for fulfilling the ConCerV criteria.

Subjects will undergo comprehensive evaluations at baseline, prior to 3 cycles of single-agent immunotherapy, and 3 weeks after its completion. The aforementioned assessments will include magnetic resonance imaging (MRI), ThinPrep cytologic test (TCT), human papillomavirus (HPV) testing, and colposcopy with biopsy. All imaging will be assessed by independent central reviewers. Treatment will be discontinued in the event of any of the following criteria: a tumor diameter that exceeds 2 cm (as determined by the largest measurement on imaging or colposcopy), the emergence of new lesions, the absence of a pathological response, intolerable toxicity, the withdrawal of informed consent, or the investigator’s decision to terminate therapy. Pathological response is defined by either the absence of tumor cells or the presence of residual tumor cells demonstrating the following modifications: 1) neoplastic nuclei show enlargement in size with irregular outlines; 2) the cytoplasm is either intensely eosinophilic or clear with vacuolated or foamy appearance; and 3) multinucleated giant cells (foreign body-like) may be observed [20]. The study will be conducted in 2 stages:

  • Stage 1: Patients who are enrolled in the first stage and complete treatment with residual tumors ≤2 cm, no evidence of new lesions, and biopsy results showing pathological response will undergo cervical conization combined with pelvic lymphadenectomy or sentinel lymph node (SLN) mapping. Patients who meet the ConCerv criteria (repeat conization is allowed once to achieve negative margins) will undergo follow-up evaluations (including TCT, HPV testing, and colposcopy biopsy) at three months. Patients whose conization fails to meet the ConCerv criteria will proceed to radical trachelectomy.

  • Stage 2: Patients enrolled in this stage will receive subsequent treatment based on the imaging evaluation after 3 cycles of immunotherapy. Patients with tumors ≤2 cm, no new lesions, and a pathological response will undergo pelvic lymphadenectomy or SLN mapping. Patients with biopsy-confirmed low-grade squamous intraepithelial lesion (LSIL) or lower will undergo re-evaluation three months later using TCT, HPV testing, and a colposcopy biopsy. Patients with biopsy results indicating high-grade squamous intraepithelial lesion (HSIL) or higher will undergo cervical conization. If conization fails to meet the ConCerv criteria, radical trachelectomy will be performed. Follow-up evaluations will be conducted three months after conization or radical trachelectomy.

Histological examination of the conization samples and lymph node will be performed at a local laboratory. All patients undergoing SLN mapping will require ultrastaging of the lymph nodes.

All patients will undergo TCT, HPV testing, and colposcopy biopsy 3 months after treatment completion.

  • (1) For patients who previously underwent biopsy only: If TCT shows ≤LSIL and colposcopy biopsy confirms no LSIL or higher-grade lesions, attempts at pregnancy may be considered five months after discontinuation of immunotherapy. If biopsy reveals ≥LSIL or cytology indicates ≥HSIL, cervical conization is recommended. Subsequent management, including observation, pregnancy planning, or repeat surgery, should follow the American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines based on postoperative findings.

  • (2) For patients who previously underwent cervical conization: If TCT is ≤LSIL and colposcopy biopsy detects no LSIL or higher-grade lesions, pregnancy attempts may be initiated five months after cessation of immunotherapy. In cases where biopsy shows ≥LSIL or cytology is ≥HSIL, further treatment should be administered according to ASCCP guidelines.

  • (3) For patients who previously underwent radical trachelectomy: If TCT shows ≤LSIL and colposcopy biopsy identifies no LSIL or higher-grade lesions, pregnancy may be attempted five months after immunotherapy is discontinued. If biopsy shows ≥LSIL or cytology is ≥HSIL, recurrence of cervical cancer must be ruled out. For those diagnosed with vaginal intraepithelial neoplasia, individualized management should be guided by FIGO recommendations.

For patients in either stage, concurrent chemoradiotherapy (CCRT) is recommended if the lymph nodes are positive. Patients undergoing radical trachelectomy who meet the Sedlis criteria should receive adjuvant radiotherapy according to the National Comprehensive Cancer Network (NCCN) guideline.

In addition to the aforementioned biopsies, cervical exfoliated cell and peripheral blood samples will be collected at multiple time points to assess exploratory endpoints and to identify biomarkers predictive of favorable treatment response. Samples will be obtained at baseline, prior to combination chemoimmunotherapy, prior to single-agent immunotherapy, prior to post-immunotherapy biopsy assessment, and three months post-treatment.

The study was supervised by an independent data monitoring committee, and all data were deidentified prior to analysis. The primary endpoint results will be reported 4 months after the enrollment of the last patient, with a final 5-year follow-up analysis planned thereafter.

3. Endpoints

The primary endpoint is the pCR rate, defined as the proportion of patients showing no evidence of invasive tumor cells and pathologically confirmed negative lymph node metastases. Participants with missing pCR data (including those who experience disease progression or do not undergo surgery) will be classified as not having achieved pCR.

Secondary endpoints include the HPV negative conversion rate, pregnancy rate, miscarriage rate, live birth rate, preterm birth rate, incidence of adverse events (including surgical complications and adverse events related to chemotherapy and immunotherapy), quality of life (assessed using the EORTC QLQ-C30 [V3], QLQ-CX24, EQ-5D-5L VAS questionnaires), event-free survival (EFS), and overall survival (OS).

Exploratory endpoints comprise molecular profiling of cervical exfoliated cells (including HPV integration sites and DNA methylation status), cytopathological features, dynamics of plasma-free HPV DNA levels, as well as serial changes in serological immune-related factors and cellular components throughout treatment and during follow-up.

4. Eligibility criteria

Inclusion criteria

1) Clinical diagnosis of FIGO (2018) stage IB1 cervical cancer based on gynecological examination and MRI evaluation.

2) Pathologically confirmed diagnosis of cervical squamous cell carcinoma.

3) Transformation zone of TZ1 or TZ2 (the International Federation of Cervical Pathology and Colposcopy, 2011).

4) Positive PD-L1 expression (CPS ≥1).

5) Patient age ≥18 years and ≤45 years.

6) Eastern Cooperative Oncology Group score ≤1.

7) Laboratory tests: white blood cell ≥3.5×109/L, neutrophil ≥1.5×109/L, platelet ≥100×109/L, serum bilirubin ≤1.5 times the upper limit of normal, aminotransferase ≤1.5 times the upper limit of normal, and blood urea nitrogen and creatinine within normal limits.

8) Have a strong desire to give birth.

9) Willingness to sign the informed consent form, including compliance with the requirements and restrictions listed therein.

Exclusion criteria

1) Patients deemed unable to achieve pregnancy even with assisted reproductive technology after comprehensive evaluation by reproductive specialists, including but not limited to: ① Profoundly diminished ovarian reserve or complete failure of oocyte generation, defined by anti-Müllerian hormone <0.1 ng/mL, repeated follicle-stimulating hormone elevations ≥40 IU/L on ≥2 measurements 4–6 weeks apart, or prior ovarian stimulation cycles yielding no retrievable oocytes; ② Uterine environments incapable of supporting implantation or sustaining pregnancy, such as endometrial thickness <5 mm across ≥3 consecutive cycles without improvement despite standardized estrogen supplementation, or diffuse myometrial scarring and compromised uterine perfusion that fundamentally preclude normal implantation and gestational maintenance; ③ Severe systemic medical conditions for which pregnancy is considered contraindicated, including but not limited to advanced heart failure or severe pulmonary arterial hypertension; ④ Genetic or gonadal disorders that result in complete failure of oocyte or embryo development.

2) Any active autoimmune disease or history of autoimmune disease requiring systemic treatment, including but not limited to autoimmune hepatitis, interstitial pneumonitis, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, thyroid dysfunction, asthma requiring bronchodilator intervention.

3) Prior treatment with immune checkpoint inhibitors, including anti-PD-1, anti-PD-L1, or other analogous agents; known hypersensitivity to any component of the investigational drug or other monoclonal antibodies.

4) History of human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.

5) Use of immunosuppressive medications or systemic corticosteroid therapy (>10 mg/day prednisone or equivalent) for immunosuppressive purposes within 14 days prior to study treatment initiation.

6) History of prior primary malignancy, or previous chemotherapy or pelvic radiation therapy.

7) Concurrent participation in other clinical trials.

8) Pregnant or breastfeeding females. Patients must agree to use effective contraception during the study and for at least 5 months after their last use of immune checkpoint inhibitors and for at least 6 months after their last use of chemotherapeutic agents. This requirement also applies if there is no confirmation of lesion removal or pathological response.

9) Uncontrolled comorbidities, including but not limited to: New York Heart Association class II or higher heart failure, severe/unstable angina, myocardial infarction within 6 months prior to study treatment, cerebrovascular accident or transient ischemic attack within 6 months prior to study treatment, any neurocognitive dysfunction, coagulation disorders (international normalized ratio >2.0, prothrombin time >16 seconds), bleeding tendency, or undergoing thrombolytic or anticoagulant therapy, abnormalities in hepatic or renal development or a history of surgery, or an active infection requiring systemic anti-infective therapy within 14 days prior to the first study dose.

10) Treatment with a live or attenuated vaccine within four weeks prior to the first study dose. However, an inactivated seasonal influenza virus vaccine is permitted.

11) Patients who have received an allogeneic bone marrow or solid organ transplant.

12) Drug and/or alcohol abuse.

13) Patients who, in the investigator’s opinion, are unlikely to comply with the study’s procedures, restrictions, and requirements may not participate in this study.

5. Sample size

Based on published clinical data, the pCR rate of neoadjuvant chemotherapy in patients with stage IB1 cervical cancer is approximately 26%. We hypothesize that the addition of a PD-1 inhibitor to chemotherapy will increase the pCR rate to 50%. The study is designed using Simon’s two-stage optimal design with a one-sided α of 0.025 and 80% power. In the first stage, 11 patients will be enrolled; if three or fewer achieve pCR, the trial will be terminated early for futility. Otherwise, an additional 25 patients will be enrolled in the second stage, yielding a total of 36 evaluable patients. If 15 or more of the 36 patients achieve pCR, the null hypothesis will be rejected, and the regimen will be considered effective, achieving a pCR rate of at least 50%. To account for an anticipated 10% dropout rate, the total sample size will be set at 40 patients.

6. Randomization and blinding

This trial is an open-label clinical trial and does not involve randomization.

7. Statistical methods

Baseline data analysis, as well as efficacy and safety evaluations, will be performed using the full analysis set (FAS), defined according to the intention-to-treat principle and including all participants who receive at least one dose of the study drug. The activity analysis set (AAS) comprise all participants in the FAS who substantially completed 6 cycles of treatment in strict adherence to the protocol and had records of cervical conization or biopsy-based pathological evaluation. Consistency between the FAS and AAS results will strengthen the reliability and robustness of the findings.

The safety set (SS) will include participants who receive at least one dose of the study drug, whereas the pregnancy outcome set (POS) will include participants with documented pregnancy intention during the follow-up period, excluding those without such intention before data lock. Safety analyses will be based on the SS, and fertility-related assessments will be conducted using the POS. Descriptive statistics will be applied according to variable type: continuous variables will be summarized as mean ± standard deviation or as median with interquartile range; categorical variables will be presented as frequencies and percentages; and time-to-event outcomes will be estimated using the Kaplan–Meier method to determine survival rates and median survival times. The primary endpoint will be analyzed using a one-sided significance level of α=0.025. Where appropriate, 2-sided 95% confidence intervals (CIs) will be reported for all estimates.

8. Treatment

Paclitaxel for injection (albumin-bound, nab-paclitaxel): Administered at 260 mg/m2 via intravenous infusion over 30 minutes on Day 1 of each cycle.

Cisplatin: Administered at 75–80 mg/m2 via intravenous infusion at a rate of 1 mg/min, divided between Day 1 and Day 2 of each cycle.

Nab-paclitaxel and cisplatin will be administered during 1 cycle of priming chemotherapy and 2 cycles of combination chemoimmunotherapy. There is a 21-day interval between chemotherapy cycles.

Camrelizumab: A PD-1 inhibitor (brand name AiRuiKa, SHR-1210) will be administered at a dose of 200 mg via intravenous infusion over 30–60 minutes. During the 2 cycles of combination chemoimmunotherapy, camrelizumab will be given 24 hours after completion of chemotherapy. During the subsequent 3 cycles of immunotherapy, camrelizumab will be administered on Day 1 of each 3-week cycle.

All the drugs used in this trial are approved and commercially available. Cisplatin has been in clinical use for nearly 2 decades. Nab-paclitaxel (brand names Keaili, Aiyue, and Ruibei) and camrelizumab have been available since receiving approval. The treatment regimen does not include any investigational or non-marketed agents.

9.Ethics

This study has been approved by the Institutional Review Board of Tongji Medical College, Huazhong University of Science and Technology (approval No.: 2024(S020)-1). Administrative authorization was obtained from all participating institutions prior to study initiation. Written informed consent will be obtained from all participants before enrollment. Any necessary protocol modifications will be implemented with subsequent IRB approval.

10. Trial registration ID

ClinicalTrials.gov Identifier: NCT06289062

DISCUSSION

This study represents the first prospective, multicenter clinical trial that investigates chemoimmunotherapy as a fertility-preserving, surgery-free strategy for stage IB1 cervical cancer. The approach introduces a paradigm shift from surgery-dominated management to a focus on organ- and function-preserving treatments.

An increasing proportion of cervical cancer diagnoses are being observed in younger women, underscoring the pressing need for treatment strategies that not only achieve optimal oncologic outcomes but also preserve fertility, particularly for those with childbearing aspirations. Current fertility-sparing approaches for early-stage cervical cancer typically involve surgical resection of cervical lesions. Nonetheless, these procedures present significant drawbacks, including risks of cervical incompetence, stenosis, and an increased likelihood of miscarriage and preterm birth [7].

The combination of ICI in neoadjuvant treatment has shown promising results in several solid tumors, including rectal cancer, where surgery-free treatment is now a feasible strategy [21]. Our group innovatively applied NACI regimen in patients with locally advanced cervical cancer, consisting of one cycle of priming chemotherapy, followed by two cycles of combined chemotherapy and immunotherapy. In that study, NACI therapy achieved a 98% overall objective response rate and a pathological response rate to 38% in FAS [19]. These findings suggest that incorporating ICI into conventional neoadjuvant chemotherapy may significantly increase the pCR rate, offering a new potential pathway for surgery-free fertility-sparing treatment in early-stage cervical cancer.

To further enhance patient safety and improve response assessment, we incorporated insights from the “watch-and-wait” strategy used in rectal cancer following neoadjuvant therapy. Evidence indicates that an observation period of up to six months may be necessary to fully identify patients achieving a clinical complete response [21]. Therefore, we included 3 additional cycles of immunotherapy to consolidate antitumor immunity and allow sufficient time for accurate pathological response evaluation. In this study, patients may attempt pregnancy five months after the discontinuation of chemoimmunotherapy. Current evidence suggests that the impact of platinum-based chemotherapy on fertility is relatively modest. A recent study reported no significant difference in the five-year incidence of infertility between patients who received platinum-based chemotherapy and those who did not [22]. Although the clinical impact of ICIs on human reproduction remains incompletely elucidated, the NCCN guidelines recommend all patients of reproductive age use effective contraception during and for at least 5 months after the last dose of immunotherapy, which corresponds to at least 5–10 half-lives of the drug [23,24]. The prescribing information for camrelizumab recommends a shorter contraception period of 2 months after treatment completion; therefore, the five-month contraception interval adopted in this study is likely to provide an adequate margin of safety.

While fertility preservation is an important objective, our protocol integrates a systematic approach for the evaluation and surveillance of survival outcomes. Cytological abnormalities are an important risk factor for the underdiagnosis of HSIL in colposcopy-guided biopsies. The Kaiser Permanente Northern California study demonstrated that, among women with biopsy results reported as normal or ≤ cervical intraepithelial neoplasia grade 1 (CIN1), the risk of underlying CIN3+ correlated with preceding cytology findings [25]. In line with ASCCP guidelines [26], which recommend stratified management based on pre-colposcopy cytology, patients in our study with biopsy results ≤LSIL will undergo further risk-adapted evaluation. To improve diagnostic accuracy, imaging was used for preliminary screening, followed by multiple biopsies for pathological confirmation. A biopsy result of <LSIL was established as the threshold for defining pathological response to minimize the risk of undetected residual disease. Patients with LSIL findings in biopsy will be managed according to cytology-based stratification to ensure the absence of residual lesions after treatment.

This study has several limitations. Some patients may exhibit limited sensitivity to the chemoimmunotherapy regimen, necessitating additional treatment and potentially delaying definitive therapy. To mitigate this risk, we implemented a Simon 2-stage trial design and incorporated exploratory endpoints to identify predictive biomarkers. Although current evidence suggests that the impact of platinum-based chemotherapy on fertility is relatively modest, its potential impact on ovarian function cannot be overlooked. Additionally, ICIs may have the potential to impair both immediate and future fertility [27]. Therefore, this study includes serial monitoring of sex hormones and follicular development to evaluate the impact of the treatment regimen on ovarian reserve, thereby achieving a balance between anti-tumor efficacy and fertility preservation. Assisted reproductive technologies offer a viable backup option for fertility preservation. Moreover, the study population is limited to patients with PD-L1-positive squamous cell carcinoma. Generalization of the findings to broader populations will require further validation through larger and more diverse datasets.

In conclusion, this trial seeks to evaluate a novel fertility-preserving, surgery-free strategy for patients with stage IB1 cervical cancer. If successful, this approach may reshape clinical practice by offering a safe and structurally non-invasive alternative that aligns reproductive goals with oncologic safety.

Footnotes

Funding: This work was supported by the National Natural Science Foundation of China (82573513, 82401905), Hubei Provincial Science and Technology Program (2025BCB011, 2023BCA004), the China Postdoctoral Science Foundation (2025M772048), and the National Clinical Research Center of Obstetrics and Gynecology (2015BAI13B05). We thank Jiangsu Hengrui Medicine for providing camrelizumab free of charge. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the study.

Conflict of Interest: No potential conflict of interest relevant to this article was reported.

Author Contributions:
  • Conceptualization: S.C., C.G., L.K.
  • Formal analysis: C.J.
  • Funding acquisition: L.K.
  • Investigation: H.Y.1
  • Methodology: H.Y.1, C.H., C.J.
  • Resources: C.G., L.K.
  • Supervision: H.Y.2, S.C., C.G., L.K.
  • Validation: H.Y.2
  • Writing - original draft preparation: H.Y.1, C.S., C.J.
  • Writing - review & editing: H.Y.1, C.J.

1H.Y., Yingjie Hu; 2H.Y., Yingyan Han.

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Articles from Journal of Gynecologic Oncology are provided here courtesy of Asian Society of Gynecologic Oncology & Korean Society of Gynecologic Oncology and Colposcopy

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