Abstract
Objective
To preliminarily explore and validate the role of E7 oncoprotein self-sampling and self-testing in cervical cancer screening.
Methods
Approved by the Ethics Committee of Peking University First Hospital, 461 patients who underwent cervical cancer screening with abnormal screening results in the outpatient clinic from June 13, 2023 to August 29, 2023 were selected and participated in the clinical trial with informed consent. For E7 oncoprotein, the participants use self-sampling brushes to collect samples and perform testing by themselves. Self-sampling and self-testing of E7 oncoprotein detection, and cervical cancer cell cytology combined with high-risk HPV detection, were performed at the same time. The experimental steps were performed according to the instructions of the E7 Protein Test Kit (Colloidal Gold Method) of FAMID Biomedical Technology (Tianjin) Co., Ltd.
Results
Among the 461 patients, 452 had valid self-sampling results. Among the 452 patients, 293 needed to be referred for colposcopy, and 34 cervical intraepithelial neoplasia (CIN)1 + patients were identified. The performance of cytology to identify CIN1 + had a sensitivity of 73.53%, specificity of 89.47%, negative predictive value of 97.65%, positive predictive value of 36.23%, and coincidence rate of 88.27%, respectively. The performance of any of the 14 high-risk HPV types to identify CIN1 + had a sensitivity of 82.35%, specificity of 59.33%, negative predictive value of 97.64%, positive predictive value of 14.14%, and coincidence rate of 61.06%. The performance of cytology combined with high-risk HPV to identify CIN1 + had a sensitivity of 77.94%, specificity of 74.40%, negative predictive value of 97.64%, positive predictive value of 25.19%, and coincidence rate of 74.67%. The sensitivity of self-sampling and self-testing of E7 oncoprotein was 76.47%, the specificity was 91.87%, the negative predictive value was 97.96%, the positive predictive value was 43.33%, and the coincidence rate was 90.71%. The coincidence rate of self-sampling and self-testing of E7 oncoprotein combined with cytology and high-risk HPV screening was 82.69%.
Conclusion
The expression of E7 oncoprotein is closely related to cervical precancerous lesions. The self-sampling and self-testing of E7 oncoprotein had a negative predictive value of 97.96% for identifying CIN1+, and had high sensitivity and specificity. It can be used independently or with combined screening with a compliance rate of 82.69%, which can help increase the cervical cancer screening coverage.
Keywords: E7 oncoprotein, Cervical cancer screening, Self-sampling and self-testing, Cervical precancerous lesions
Background
Cervical cancer is an important issue in the field of women’s health. Fortunately, before cervical cancer occurs, it often goes through a long process from persistent Human papillomavirus (HPV) infection to cervical intraepithelial lesions and then to invasive cervical cancer, which provides a key opportunity for the prevention and control of cervical cancer. Since most cervical precancerous lesions and even early cervical cancer are not accompanied by obvious symptoms, screening is particularly important. Although the global cervical cancer burden has decreased, significant regional disparities remain [1]. Moreover, it is worrying that many women fail to undergo cervical cancer screening due to various reasons such as reproductive tract examinations, fear of pain during gynecological examinations, and inconvenient transportation, thus becoming a “potential risk group” for cervical cancer. Screening coverage is one of the key factors to ensure the success and widespread application of screening. Only when more women participate in screening, can we find more patients with cervical precancerous lesions and provide them with opportunities for early intervention and treatment. The introduction of self-sampling and self-testing screening methods will play a key role in increasing the coverage of cervical cancer screening. This screening method allows women to collect cervical cell samples and self-test at home without going to a medical institution, making it more convenient, easy and feasible, which is conducive to lowering the threshold for cervical cancer screening and increasing screening coverage. Especially for women living in remote areas or with difficulty in accessing medical services, and those who are unwilling or have no time to go to the hospital for cervical cancer screening for various reasons, this provides a more convenient screening option, helps extend cervical cancer screening to a wider population, and increases the chance of early diagnosis.
High-risk HPV (hr-HPV) is an important factor causing cervical cancer. Its oncogene E7 is integrated into the human genome and expressed as E7 oncoprotein [2]. The latter binds and degrades retinoblastoma protein (pRb) and activates protein 1 (AP-1) transcription factor family, causing the cell cycle of infected cells to lose control, leading to unlimited cell proliferation and mutation. E7 oncoprotein is closely related to the occurrence and development of cervical cancer [3].
This study will explore the advantages of self-sampling and self-testing screening of E7 oncoprotein, as well as the importance of actively promoting this method. This method is expected to play a key role in cervical cancer screening, provide more women early detection opportunities of cervical precancerous lesions, and thus make greater contributions to protecting women’s health.
Materials and methods
Research design and subjects
Women who underwent cervical cancer joint screening in the Department of Obstetrics and Gynecology of Peking University First Hospital from June 13, 2023 to August 29, 2023 were selected as potential research participants. The age distribution of participants includes 23–39 years 37.19%, 40–59 years old 48.75%, and 60–74 years old 14.06%, with an average of 45 ± 11.9 years.
Inclusion criteria: ① Complete information on cervical cytology (ThinPrep Cytology, LBC) and any of 14 types of high-risk HPV test results; ② Agree and sign the informed consent form; ③ If they meet the conditions for referral colposcopy, they will voluntarily undergo colposcopy; ④ If the colposcopy is abnormal, they will undergo biopsy and have cervical histopathological diagnosis results.
Exclusion criteria: ① Difficulty in obtaining specimens due to self-sampling; ② Acute vaginitis, acute cervicitis; ③ Irregular vaginal bleeding; ④ Continuous vaginal discharge; ⑤ Women after total hysterectomy, during pregnancy, and during lactation.
Research methods
A prospective research method was used to explore the distribution of E7 oncoprotein in different cytology and high-risk HPV types, and to validate the correlation between E7 oncoprotein and cervical cancer self-sampling and self-testing screening method and its diagnostic efficacy for cervical lesions (CIN1+). The detection of E7 oncoprotein is to identifythe expressions of E7 oncoprotein. The expression of E7 oncoprotein leads to cervical precancerous lesions, and the stages of precancerous lesions include CIN1-3. The E7 oncoprotein identification of this study starts from CIN1 + cervical precancerous lesions.
E7 oncoprotein test kit provided by FAMID Biomedical Technology (Tianjin) Co., Ltd. uses lateral flow technology and sandwich immunoassay. During detection, the sample crawls up along the test strips to dissolve the colloidal gold conjugate. If there is E7 oncoprotein in the sample, the E7 protein will combine with the detection antibody-colloidal gold conjugate to form Ag-Ab-colloidal gold conjugate. The band is the T line, which represents a positive result. If the sample does not contain E7 protein, there will be no visible red band at the test line position, which represents a negative result. The ROC curve of E7 oncoprotein concentration was analyzed, and the AUC showed 0.718 (95% CI 0.628–0.808).
All participants were given instructions based on the user guides of self-sampling brush and E7 oncoprotein test kit, which have detailed instructions for self-sampling and self-testing. High-risk HPV E7 oncoprotein detection method: ① Gently turn the test tube containing the sample release agent upside down three times, place the test tube on a flat surface, and proceed to the next step. ② Take a comfortable standing posture, insert the disposable brush into the vagina, and rotate the brush rod counterclockwise for 6 rotations. After taking the sample, insert the cervical sampling brush into the test tube, press down gently, and put it in place. ③ Fix the sampling brush with one hand, and gently push the sampling brush with the other hand, immerse the brush head in the liquid, and when the brush head touches the bottom of the test tube, rotate it 10 times to allow the brush head to fully scrape the ribs at the bottom of the reagent bottle. ④ After the sample is processed, start the test. The E7 oncoprotein test result is positive if there are double lines; negative if there is a single line; invalid if there is no result due to heavy bleeding or secretions.
Cervical cytology: ThinPrep cytology was used, and the diagnosis was made according to the 2014 The Bethesda System (TBS). According to the 2019 American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines [4], atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesions (ASC-H), high-grade squamous intraepithelial lesions (HSIL), atypical glandular abnormalities (AGC-NOS/AGC-FN), adenocarcinoma in situ (AIS), cervical squamous cell carcinoma cells (SCC), and cervical adenocarcinoma cells (ADCA) were defined as “high-grade test results”; atypical squamous cells of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion cells (LSIL) were defined as “low-grade test results”. Positive cervical cytology was defined as: ≧ASCUS, and the negative group was defined as NILM.
High-risk HPV detection method: Detection of 14 high-risk HPV types using Cobas Roche, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68. The single HPV positive group is the HPV16 and/or HPV18 group.
Colposcopy: Colposcopy should be performed according to the standardized colposcopy procedure and according to the group standard of the “Guidelines for the Diagnosis and Treatment of Cervical Precancerous Lesions” [5]. Women who meet the conditions such as LBC-/HPV16+, LBC-/HPV18+, LSIL/hrHPV+, ASCUS/hrHPV+, ASC-H/hrHPV+, HSIL/hrHPV-, AGC-NOS/hrHPV+, HSIL/hrHPV+, AGC-NOS/hrHPV-, or ASC-H/hrHPV will undergo colposcopy [5]. Risk stratification of cervical lesions should be performed according to the 2019 ASCCP guidelines, and patients with a CIN3 + risk of ≥ 4% should be referred for colposcopy. The colposcopy findings are classified into: suspected invasive cervical cancer, cervical HSIL, cervical LSIL, no abnormalities found during colposcopy (high-level examination results), cervical bleeding, cervical hyperplasia and vegetation, and normal colposcopy findings. Patients with suspected invasive cervical cancer, cervical HSIL, cervical LSIL, no abnormalities found during colposcopy (high-level examination results), cervical bleeding, and cervical hyperplasia and vegetation should undergo a localized biopsy.
Pathological examination method: According to the World Health Organization (WHO) Classification of Female Reproductive Organ Tumors [6] (2020 edition), pathological tissues are classified into: normal or inflamed cervix, low-grade squamous intraepithelial lesions (LSIL, CIN1 and condyloma lesions), high-grade squamous intraepithelial lesions (HSIL, CIN2 and CIN3), adenocarcinoma in situ (AIS) and cervical cancer (including microinvasive carcinoma and invasive carcinoma).
Cervical lesion grouping criteria: The cervical lesion group refers to patients with CIN1 + lesions indicated by biopsy pathology; the normal cervix group refers to patients with cervical cytology combined with HPV test results indicating an immediate CIN3 + lesion risk of less than 4%, or patients with colposcopy findings suggesting normal colposcopy or biopsy pathology indicating chronic inflammation.
Statistical analysis
SPSS 22.0 software was used for data processing and statistical analysis. The age, cytology and high-risk HPV screening results, colposcopy image characteristics, and histopathological distribution (frequency, percentage) of 452 women who underwent colposcopy were analyzed using the χ2 test.
Results
452 subjects were enrolled in the study. Before participants received E7 resting, they had both cytology and HPV testing first, and then they received E7 testing. All participants were given instructions on sample collection and testing by participants at the clinic. In cervical cytology, NILM was found in 383 cases (84.73%) and abnormal in 69 cases (15.27%); high-risk HPV test was negative in 254 cases (56.73%) and positive in 198 cases (43.81%); 293 cases were referred for colposcopy, of which 39 cases (13.31%) had abnormal colposcopy and 254 cases (86.69%) were normal; histopathological results showed that there were 8 patients with CIN3, 20 patients with CIN2, and 6 patients with CIN1. Therefore, there were 34 cases (7.52%) in the cervical lesion group (CIN1+); and 418 cases (92.48%) in the normal cervical group.
In this study, 452 cases were effectively tested for E7 oncoprotein, of which 60 cases were positive for E7 oncoprotein and 392 cases were negative (see Table 1).
Table 1.
Results of four detection methods
| Test Methods | Test Results | n | % |
|---|---|---|---|
| Cytology | |||
| NILM | 383 | 84.74% | |
| ASC-US | 31 | 6.86% | |
| LSIL | 20 | 4.42% | |
| ASC-H | 11 | 2.43% | |
| HSIL | 6 | 1.33% | |
| AGC | 1 | 0.22% | |
| HR-HPV | |||
| Negative | 254 | 56.19% | |
| Positive | 198 | 43.81% | |
| HPV 16/18(+) | 72 | 15.93% | |
| other-12(+) | 126 | 27.88% | |
| E7 Oncoprotein | |||
| E7(+) | 60 | 13.27% | |
| E7(-) | 392 | 86.73% | |
| Colposcopy | |||
| Ca | 0 | 0.00% | |
| HSIL | 29 | 9.90% | |
| LSIL | 5 | 1.71% | |
| NILM (HG) | 2 | 0.68% | |
| Blooding | 0 | 0.00% | |
| Neoplasm | 3 | 1.02% | |
| NILM | 254 | 86.69% | |
| Histopathology | |||
| Ca | 0 | 0.00% | |
| CIN3 | 8 | 20.51% | |
| CIN2 | 20 | 51.29% | |
| CIN1 | 6 | 15.38% | |
| Inflammation | 5 | 12.82% | |
Distribution of E7 oncoprotein expression in cervical cytology and its correlation analysis
According to this study, the sensitivity of cervical cytology is 73.53% and the specificity is 89.47, which is close to the sensitivity of E7 oncoprotein 76.47% and the specificity 91.87%. The expression of E7 oncoprotein in the abnormal cervical cytology group was significantly increased, and the expression of E7 oncoprotein was correlated with the severity of cervical cytology abnormality. The average correlation value of ASCUS + was 75% (see Table 2).
Table 2.
Distribution of E7 oncoprotein test results in cytology
| NILM | ≧ASCUS | ASCUS | LSIL | ASC-H | HSIL | AGC | |
|---|---|---|---|---|---|---|---|
| E7(-) | 344(89.82%) | 48(69.57%) | 25(80.65%) | 13(65.00%) | 7(63.64% | 2(33.33%) | 1(100.00%) |
| E7(+) | 39(10.18%) | 21(30.43%) | 6(19.35%) | 7(35.00%) | 4(36.36%) | 4(66.67%) | 0(0.00%) |
| 383 | 69 | 31 | 20 | 11 | 6 | 1 |
Distribution of E7 oncoprotein in high-risk HPV DNA test results
The distribution of E7 oncoprotein test results is as follows (see Table 3). There were 254 cases with negative high-risk HPV, 198 cases with positive high-risk HPV, including 72 cases with positive 16 and 18, and 126 cases with other 12 high-risk types. High-risk HPV had a higher sensitivity of 82.35%, but a lower specificity of 59.33%. The sensitivity of E7 oncoprotein was 76.47%, and the specificity was 91.87%, which was higher than that of high-risk HPV.
Table 3.
Distribution of E7 oncoprotein test results in High-Risk HPV
| HPV(-) | HR-HPV(+) | HPV16(+) | HPV18(+) | Other 12 HPV(+) | |
|---|---|---|---|---|---|
| E7(-) | 222(87.40%) | 170(85.86%) | 49(77.78%) | 7(87.50%) | 114(89.76%) |
| E7(+) | 32(12.60%) | 28(14.14%) | 14(22.22%) | 1(12.50%) | 13(10.24%) |
| 254 | 198 | 63 | 8 | 127 |
Expression of E7 oncoprotein in different risk groups of cervical lesions
Combined with the results of cervical cytology and HPV testing, the subjects were divided into three groups according to ASCCP risk stratification, and the group of “immediate CIN3 + risk value less than 4 but with immediate cancer risk” was further added. See Table 4 for the expression of E7 oncoprotein in each group.
Table 4.
Distribution of E7 oncoprotein test results in cytology
| Immediate Risk of CIN3+ | ||||
|---|---|---|---|---|
| <4% Group | 4–24% Group | ≥ 25% Group | Immediate CIN3 + risk value is less than 4 But there is an immediate risk of cancer |
|
| E7(-) | 321(87.47%) | 66(84.62%) | 5(71.43%) | 1(100.00%) |
| E7(+) | 46(12.53%) | 12(15.38%) | 2(28.57%) | 0(0.00%) |
| 367 | 78 | 7 | 1 | |
Comparison of the performance of E7 oncoprotein detection and other cervical cancer screening strategies to identify CIN1+
When predicting cervical lesions (CIN1+), E7 oncoprotein detection had a sensitivity of 76.47% and a specificity of 91.87%, and the E7 oncoprotein specificity was higher than the other three detection methods. Pathological results show that it had a higher compliance rate. E7 oncoprotein detection also had higher positive and negative predictive values for cervical lesions, which were 43.33% and 97.96% respectively (see Table 5).
Table 5.
Efficacy of four screening methods in identifying CIN1+
| Sensitivity | Specificity | NPV | PPV | Compliance Rate | |
|---|---|---|---|---|---|
| Cytology | 73.53% | 89.47% | 97.65% | 36.23% | 88.27% |
| HR-HPV | 82.35% | 59.33% | 97.64% | 14.14% | 61.09% |
| Combined Cytology/HR-HPV | 77.94% | 74.40% | 97.64% | 25.19% | 74.67% |
| E7 | 76.47% | 91.87% | 97.96% | 43.33% | 90.71% |
Discussion
Cervical cancer is one of the most common malignant tumors in women, and HPV is its main cause. According to the gene structure, the early transcription region (E region) of the HPV genome consists of 4500 base pairs, encoding 8 early proteins, namely E1, E2, E3, E4, E5, E6, E7, and E8 [7], which have functions such as participating in viral DNA replication, transcription, translation regulation, and cell transformation; among them, E6 and E7 oncoproteins are mainly related to the virus cell transformation function and carcinogenicity.
The oncogenic protein encoded by the E7 gene is an important factor in causing cervical epithelial carcinogenesis. The E7 protein is an oncoprotein that inhibits the normal apoptosis process of cells and induces an acceleration of the cell division cycle. This protein inhibits pRb so that infected cells can proliferate indefinitely and undergo malignant transformation. The expressions of E7 oncoprotein cause cells to undergo high-grade precancerous lesions and eventually become cancerous. High-risk HPV E7 oncoprotein can immortalize human primary keratinocytes, promote genomic instability, and drive tumor formation in vivo models. High-risk HPV E6 can cause a variety of carcinogenic phenotypes and increase the efficiency of E7-mediated keratinocyte immortalization by activating telomerase [8]. Studies have found that high-risk HPV E7 oncoprotein is frequently expressed in cervical cancer cases, suggesting that it may be an essential component and tumor marker for cervical cancer [9].In this study, as the severity of cervical cytological abnormalities increased, E7 oncoprotein expression increased, which also indirectly verified this view.
In 2020, WHO released the Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem [10]. In order to achieve the elimination of cervical cancer, the global cervical cancer screening coverage should reach more than 70% by 2030. However, in 2019, the global coverage of women aged 30–49 was estimated to be 15% in the previous year, 28% in the previous three years, 32% in the previous five years, and 36% in their lifetime. Currently, the cervical cancer screening coverage rate is only around 30% [11]. Due to different economic development levels, medical infrastructure conditions especially in remote areas and per capita incomes of various countries, the coverage rates of cervical cancer screening vary.
Cervical cancer screening currently uses a variety of strategies and methods, including HPV testing, cytology testing alone, or cytology combined with high-risk HPV co-test.
Cervical self-sampling technology products have been used clinically for more than 10 years worldwide. The clinical application technology is mature and has been widely popularized. The analysis of hospital specialist sampling and participant self-sampling results shows that self-sampling can be used as the main screening method in routine screening [12]. Studies have shown that 80.5% of women prefer to use a brush device for self-sampling rather than doctor collection [13]. The high-risk HPV infection rate of samples collected by doctors was 8.0% (95% CI 6.9–9.2), while the high-risk HPV infection rate of self-sampling samples was 10.0% (95% CI 8.7–11.3). The consistency of high-risk HPV infection rates between self-sampling and physician-collected samples was 96.8% (95% CI 96.0–97.5) [13]. Women found self-sampling convenient (97.1%) and easy to operate (98.5%), and 62.8% of women preferred self-sampling rather than physician-collected samples for the next screening. In the responding population, the results of self-sampling and physician-collected samples for high-risk HPV were highly consistent, and women were more accepting. HPV self-sampling can be considered as the main screening tool for the responding population [13]. WHO recommends that HPV self-sampling should be offered to women aged 30 to 60 years as a supplementary method of sampling for cervical cancer screening service. In places where HPV testing is already included in national plans, the option of self-sampling may encourage women to obtain screening and treatment services and increase screening coverage. The reliability of self-sampling is as high as that of samples collected by medical institutions [14].
The E7 oncoprotein self-sampling and self-testing method enables women to collect samples and test themselves at home, greatly reducing the threshold for going to hospitals, clinics, or medical institutions for screening. For women who cannot easily receive traditional screening due to geographical location, culture, or other reasons, self-sampling and self-testing provide a more private screening method that does not require face-to-face contact with medical professionals, especially in areas with limited resources, which has a positive significance in popularizing high coverage of cervical cancer screening. In places where cervical cancer screening has been included in national plans, the option of self-sampling may encourage women to obtain screening and treatment services and increase screening coverage. Self-sampling will help achieve the global goal of 70% screening coverage by 2030. Women may prefer to collect samples themselves rather than go to a healthcare provider for cervical cancer screening. The presence and expression level of E7 oncoprotein can be used as a predictive tool to help identify which patients are more likely to develop cervical cancer, filter HPV transient infection, and triage follow-up and referral for colposcopy and biopsy.
In cervical cancer screening, avoiding missed diagnoses in E7 oncoprotein self-sampling requires a series of measures to ensure the quality and accuracy of samples (Figure 1). (1) Provide patients with clear instructions and training on how to collect samples correctly. Patients need to understand how to use self-sampling tools correctly to ensure that sufficient cervical cell samples are collected. (2) Ensure the use of high-quality self-sampling tools, including sampling brushes. The design and materials of the tools should meet standards to ensure that sufficient cell samples are collected. (3) The timing of sampling is also important. It is best to take samples when there is no obvious inflammation or bleeding in the cervix to reduce possible missed diagnoses. Some patients in this study failed the test due to excessive secretions and contact bleeding during sampling. (4) Even if the E7 oncoprotein self-sampling result is negative, regular cervical cancer screening should still be considered to ensure early detection of any potential problems. (5) Encourage patients to actively participate in the screening process and establish open communication channels so that they can consult medical professionals at any time if they have concerns or questions.
Fig. 1.
The key measures of E7 oncoprotein self-sampling and self-testing
Conclusion
E7 oncoprotein self-sampling and self-testing can allow more people to self-test at home and achieve high-quality cervical cancer screening, which has many benefits. E7 oncoprotein self-sampling and testing can help to timely identify women at high risk and take early intervention measures, making it easier to achieve regular screening and tracking, especially for those at high risk. High-coverage screening can detect cervical precancerous lesions early, save medical resources, reduce the economic burden on patients, and reduce the cost of treating cervical cancer. In addition, through self-sampling and self-testing of E7 oncoprotein, high screening coverage can also help improve the public’s awareness of cervical cancer prevention and stimulate health awareness, which also has a positive impact on the prevention of other diseases. Our study is not without limitations. In the first place, it is a single-center study with a limited sample size. Secondly, the accuracy of E7 Oncoprotein self-sampling and self-testing is, to some extent, dependent on factors such as the standardization of participants’ operations, sampling tools, and sampling time. More studies are therefore imperative to validate the clinical efficacy of E7 oncoprotein self-sampling and self-testing in multi-centers, and in large-scaled cervical cancer screening program to access the feasibility of using E7 oncoprotein as rapid at-home sampling and testing. On the side of the economic benefits, E7 oncoprotein test does not require equipment, labs or lab technicians for processing samples or performing tests. As self-sampling and self-testing test, that helps significantly reduce overhead costs at hospitals or labs. Overall, with the continuous advancement of technology, the detection and application of E7 oncoprotein will be more extensive and accurate, providing new hope for the prevention and treatment of cervical cancer, and ultimately achieving the goal of eliminating cervical cancer.
Acknowledgements
We are grateful to the research team at Peking University First Hospital for their support in data collection and analysis. Special thanks to Dr. Cui Rongrong, Dr. Li Junxia and Dr. Dong Jianxin for providing insightful feedback throughout the study.
Abbreviations
- HPV
Human papillomavirus
- hr-HPV
High-risk HPV
- pRb
retinoblastoma protein
- AP-1
activates protein 1
- WHO
World Health Organization
- LBC
Liquid Based Cytology
- CIN
cervical intraepithelial neoplasia
- TBS
The Bethesda System
- ASCCP
American Society for Colposcopy and Cervical Pathology
- ASC-H
atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesions
- HSIL
high-grade squamous intraepithelial lesions
- AGC-NOS
atypical glandular abnormalities
- AIS
adenocarcinoma in situ
- SCC
cervical squamous cell carcinoma cells
- ADCA
cervical adenocarcinoma cells
- ASCUS
atypical squamous cells of atypical squamous cells of undetermined significance
- LSIL
low-grade squamous intraepithelial lesion cells
- NILM
Negative for Intraepithelial Lesion or Malignancy
- NPV
Negative predictive value
- PPV
Positive predictive value
Authors’ contributions
The study was conceived and designed by Hui Feng, Jian Zhao and Yan Zhang. Hui Feng and Jian Zhao contributed to data collection, statistical analysis and prepared the first draft of the manuscript. Jing Zhang and Peng Jia provided critical revisions and supervised the study. Jian Zhao and Yan Zhang revised the paper and helped to write the final draft of the manuscript.
Funding
This study was supported by the National Key Research and Development Program of China (No. 2020AAA0105200). The funding agency had no role in the study design, data collection, analysis, or interpretation, the writing of the manuscript, or the decision to submit the manuscript for publication.
Data availability
The datasets analyzed during the current study are not publicly available due to the internal data management policies of the hospital and the need to comply with national medical privacy laws to protect research subjects’ confidential personal and clinical information, but are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
The study was approved by the ethics committee of the Peking University First Hospital (Approval number of ethics committee: 2023[208-002]). All sampling and experiments were performed in accordance with the approved guidelines of Ethics Committee of the Peking University First Hospital.
Consent for publication
No identifying images, personal identifiable information or clinical details that may compromise participants’ anonymity are presented in the manuscript. All research- related information of participants has been fully de-identified, so the consent for publication is not applicable to this study.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Hui Feng and Jian Zhao contributed equally to this work.
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Associated Data
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Data Availability Statement
The datasets analyzed during the current study are not publicly available due to the internal data management policies of the hospital and the need to comply with national medical privacy laws to protect research subjects’ confidential personal and clinical information, but are available from the corresponding author on reasonable request.