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CN118549652A - Application of P16 and colposcopy in persistent high-risk HPV - Google Patents

Application of P16 and colposcopy in persistent high-risk HPV
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CN118549652A
CN118549652ACN202410623190.6ACN202410623190ACN118549652ACN 118549652 ACN118549652 ACN 118549652ACN 202410623190 ACN202410623190 ACN 202410623190ACN 118549652 ACN118549652 ACN 118549652A
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cervical
detection
lesions
protein
colposcopy
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吴燕
黄明钜
舒丹
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Three Gorges Hospital Affiliated To Chongqing University
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Three Gorges Hospital Affiliated To Chongqing University
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Abstract

The invention belongs to the technical field of cervical cancer information detection, and discloses P16 and application thereof in colposcopy detection on persistent high-risk HPV, wherein cytological P16 detection is a method for judging whether abnormality occurs in cells by detecting P16 protein in the cells, and the P16 protein is over-expressed in a pre-cervical cancer lesion and is used as a marker for early cervical cancer screening. In the high-risk HPV infected population, cervical lesions can be classified by cytologic P16 detection of cervical transformation areas and combination of microscopic examination results; wherein type III lesions refer to highly abnormal cellular changes, whereas type I lesions are slightly abnormal cellular changes. Compared with the traditional liquid-based cytology detection, the combined microscopic examination has higher accuracy. Liquid-based cytology can only be used for judging whether the cells are abnormal by observing the cell morphology, and combined microscopy can be used for more accurately judging whether the cells are abnormal by detecting the expression of the P16 protein.

Description

Application of P16 and colposcopy in persistent high-risk HPV
Technical Field
The invention belongs to the technical field of cervical cancer information detection, and particularly relates to application of P16 and colposcopy in persistent high-risk HPV.
Background
Currently, cervical cancer is one of the three major malignant tumors of the female genital tract, and in China, women diagnosed with cervical cancer annually are about 6.2 ten thousand, wherein about 3 ten thousand women die from cervical cancer and have a tendency to be younger year by year. According to 2012 cervical cancer screening and premalignant lesions global consensus guidelines established by the U.S. colposcopy and cervical pathology institute (ASCCP), human papillomavirus (humanpapilloma virus, abbreviated HPV) infection detection and liquid-based thin layer cytology (LPT) combined detection are currently used clinically as main screening methods for cervical cancer. Among asymptomatic women, more than about 40% of women have been detected for HPV positives with an excessively high false positive rate. Queue studies conducted by U.S. KAISERPERMANENTE NORTHERN CALIFORNIA have found that HPV positive and cytologically negative individuals have a risk of developing pre-cervical lesions (CIN 3) and lesions above within 5 years of 4-5%. Only persistent infections with high-risk HPV cause cervical cancer and precancerous lesions, while most present with a overactive infection, and these patients are not closely related to cervical cancer. Thus, HPV detection has the disadvantage of having too low specificity. In the clinical detection process, the liquid-based thin-layer cytology detection has the defects of lower sensitivity (29% -56%), poor repeatability among observers, insufficient quality control and the like, so that the detection rate of early cervical cancer is seriously reduced, and particularly the conversion area under a colposcope or the missed diagnosis rate of cervical adenocarcinoma is higher. Even if the results of the annual liquid-based cytological examination are negative, about 10% of women develop invasive cervical cancer.
Therefore, in the high-risk HPV infected population, there is an urgent need to find a more accurate, simpler and effective classification method to increase the detection rate of precancerous lesions or cancerous lesions.
At present, various related literature researches at home and abroad report that a tumor suppressor gene P16 is also called a polyoma suppressor (MTS 1) gene or a CDKN2 gene, is an important member of NK4 family, and the coding product is P16 protein. The related histopathological research proves that the P16 protein expression has close correlation with cervical lesions such as cervical cancer, cervical intraepithelial neoplasia (CERVICAL INTRAEPITHELIALTHELIAL neoplasia, CIN) and the like, and almost up to 100 percent of the P16 protein expression has over-expression in cervical high-grade precancerous lesions and cervical cancer and has low expression in normal cervical tissues and cervical condyloma acuminatum tissues. The research shows that the positive rate of P16 expression in various cervical lesions increases with the increase of lesion degree, the expression intensity is also from weak to strong, and the P16 detection is indicated to be used as an index for diagnosing the pre-cervical cancer lesions and cervical cancer. Then, at the cytological level, p16 protein detects differences in expression in different cervical lesions, and as histologically, the positive rate of protein expression increases with increasing lesion level? Especially, the combined colposcopy is applied to the crowd infected by high-risk HPV, the specificity of the detection result can be greatly improved, and the sensitivity and the specificity of the detection result are higher especially for diagnosing CINII and above lesions. At present, the related research report literature at the present stage is relatively few in the aspects of cytology P16 detection and combined colposcopy.
Through the above analysis, the problems and defects existing in the prior art are as follows: in the clinical detection process, the liquid-based thin-layer cytology detection also has the defects of lower sensitivity (29% -56%), poor repeatability among observers and insufficient quality control.
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention provides P16 and application thereof in colposcopy in persistent high-risk HPV.
The invention is realized in such a way that the P16 protein is used as a marker for early cervical cancer screening.
Further, the application of the P16 in colposcopy in persistent high-risk HPV judges whether the cells are abnormal or not by detecting the P16 protein in the cells, and the P16 protein is over-expressed in the precancerous lesions of cervical cancer and is used as a marker for early cervical cancer screening.
Further, the use of P16 in colposcopy in persistent high-risk HPV, comprising the steps of:
Firstly, in a crowd infected by high-risk HPV, cytological P16 detection is carried out on a cervical transformation area, and a microscopic examination result is combined;
Step two, classifying cervical lesions; wherein type III lesions refer to highly abnormal cellular changes, type II lesions are moderately abnormal cellular changes, and type I lesions are mildly abnormal cellular changes.
Further, by detecting the expression of the P16 protein in combination with colposcopy, whether the cells are abnormal or not is judged.
Further, cytological P16 detection combined with colposcopy was applied to high risk HPV infection, classified sense under cervical transformation zone type III/II/I.
The invention also provides a system for early screening of cervical cancer, comprising:
sample acquisition unit: for collecting cervical transformation zone cell samples from individuals at high risk for Human Papillomavirus (HPV) infection;
p16 detection unit: the method is used for detecting P16 protein expression of the collected cell sample so as to identify whether the cells are abnormal or not;
An image acquisition unit: a colposcope is arranged for acquiring a high-definition image of a cervical transformation area;
A data analysis processing unit: receiving the P16 detection result and the data of the image acquisition unit, analyzing and processing, and classifying cervical lesions, wherein the classification comprises type III lesions (highly abnormal cell changes), type II lesions (moderately abnormal cell changes) and type I lesions (slightly abnormal cell changes);
And an output display unit: is used for displaying classification results and related images of cervical lesions and assisting clinical diagnosis and treatment decision.
Further, the system further comprises:
User interaction unit: providing a user-friendly operation interface for inputting patient information, receiving operation instructions and displaying detection and analysis results;
Database management unit: the system is used for storing and managing patient information, detection results and historical data and supporting query, statistics and backup of the data;
communication interface unit: support the data exchange with external systems such as the Hospital Information System (HIS) or Laboratory Information Management System (LIMS), etc., realize information sharing and integration;
And a quality control evaluation unit: the performance of the P16 detection unit and the image acquisition unit is evaluated and calibrated regularly, so that the accuracy and stability of the system are ensured;
Education and training unit: provides relevant operation guidance and cervical cancer knowledge education, and helps to promote cervical cancer prevention and treatment consciousness of medical staff and patients.
Another object of the invention is to provide an application of the P16 protein in early cervical lesion screening projects.
It is another object of the invention to provide the use of said P16 protein in the detection of early cervical variations in combination with cytological P16 detection and colposcopy.
In combination with the technical scheme and the technical problems to be solved, the technical scheme to be protected has the following advantages and positive effects:
First, the invention applies cytology P16 detection combined with colposcopy to high-risk HPV infected people, discusses classification sense under different types (III/I type) of cervical transformation area, evaluates whether the cervical transformation area has higher accuracy rate compared with liquid-based cytology detection, and can further improve early cervical transformation or detection rate so as to provide more reference basis for popularization and application in vast woman early cervical lesion screening projects, thereby guiding clinical treatment better.
Second, cytological P16 assay is a method for determining whether a cell is abnormal by detecting P16 protein in the cell. The P16 protein is over-expressed in precancerous lesions and is used as a marker for early cervical cancer screening. Combined colposcopy is a method that combines cytological P16 testing with colposcopy. In the high-risk HPV infected population, cervical lesions can be classified by cytological P16 detection of cervical transformation area in combination with colposcopy results. Wherein type III lesions refer to highly abnormal cellular changes, type II lesions are moderately abnormal cellular changes, and type I lesions are mildly abnormal cellular changes. Compared with the traditional liquid-based cytology detection, the combined colposcopy detection has higher accuracy. Liquid-based cytology can only be used for judging whether cells are abnormal by observing cell morphology, and combined colposcopy can be used for judging whether cells are abnormal more accurately by detecting the expression condition of P16 protein. Thus, combined colposcopy can increase the detection rate of early cervical variations. By applying cytological P16 detection in combination with colposcopy to high risk HPV infected people, the early stages of cervical lesions can be better screened, providing more opportunities for early treatment. This helps to increase the early diagnostic rate of cervical cancer and reduce the morbidity and mortality of cervical cancer.
The cytological P16 detection combined colposcopy provided by the invention has higher accuracy in the detection of early cervical variation, can improve the early screening effect of cervical lesions, and provides more accurate guidance for clinical treatment.
Thirdly, the expected benefits and commercial value after the technical scheme of the invention is converted are as follows: because the P16 protein is over-expressed in the precancerous lesions, the early cervical cancer and the precancerous lesions can be more accurately identified by using the P16 protein as a biomarker, and the risks of misdiagnosis and missed diagnosis are reduced. Proper treatment and intervention can be performed in time through accurate early diagnosis, so that the treatment success rate is improved and the medical cost is reduced. The method is particularly suitable for high-risk HPV infected people, and helps to expand the screening range of cervical cancer in the specific group.
Fourth, the cervical cancer early screening system provided by the invention realizes the following remarkable technical progress by integrating various technical means such as P16 protein detection, colposcope image analysis and the like:
1. improving screening accuracy
The system can more accurately identify and classify cervical lesion degrees by using the P16 protein as a biomarker and combining with a high-definition colposcope image. Compared with the traditional single detection means, the multi-mode fusion diagnosis method greatly improves the identification rate of lesions before cervical cancer and the accuracy of diagnosis.
2. Realizing early screening and intervention
The system performs early screening on pre-cervical cancer lesions of high-risk HPV infected people, can timely find mild abnormal cell changes (type I lesions) to high abnormal cell changes (type III lesions), provides powerful support for early treatment and intervention, and effectively reduces the incidence rate of cervical cancer.
3. Accurate lesion localization and classification
The data analysis processing unit of the system can accurately analyze the P16 protein expression condition and the colposcope image, realize accurate positioning and fine classification of cervical lesions, and provide accurate reference information for subsequent clinical treatment.
4. Improving user operation experience and management efficiency
The user interaction unit and the database management unit of the system provide a convenient operation interface and a powerful data management function for medical staff, and work efficiency and management convenience are greatly improved. Meanwhile, the education and training unit of the system can also improve the cognitive level of medical staff and patients on cervical cancer prevention and treatment.
5. Facilitating medical resource sharing
Through the communication interface unit, the system can effectively exchange and integrate data with external systems such as a Hospital Information System (HIS) or a Laboratory Information Management System (LIMS), thereby promoting the sharing of medical resources and the instant updating of information and providing continuous medical services for patients.
The cervical cancer early screening system provided by the invention not only improves the accuracy and efficiency of cervical cancer screening, but also improves the working experience of medical staff and the hospitalization experience of patients, and has important significance for improving the early discovery rate and cure rate of cervical cancer.
Drawings
FIG. 1 is a flow chart of a method for applying P16 in colposcopy to persistent high-risk HPV according to an embodiment of the invention.
Detailed Description
The present invention will be described in further detail with reference to the following examples in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Embodiment 1: p16 protein cervical cancer screening method based on cytological detection
1. Cervical cell samples are collected from individuals suspected of being infected with high risk HPV.
2. P16 protein immunostaining was performed on collected cervical cell samples using specific antibodies.
3. The cell samples were observed by microscopy and the expression of the P16 protein was assessed.
4. Judging whether the cells have cervical precancerous lesions according to the over-expression condition of the P16 protein.
Is suitable for clinical laboratories and hospitals and is used as one of routine cervical cancer screening projects.
Embodiment 2: p16 protein cervical cancer screening system combined with colposcopy
1. Colposcopy is performed on individuals infected with high risk HPV to determine the specific location of cervical transformation zone.
2. Cervical cell samples were accurately collected from the transformation area under colposcopic guidance.
3. Immunostaining of the P16 protein was performed on the collected cell samples.
4. And comprehensively evaluating the risk of the precancerous lesion by combining the colposcopy result and the P16 protein expression condition.
The cervical cancer risk assessment method is suitable for gynecological outpatient service, and particularly suitable for more accurate cervical cancer risk assessment of high-risk patients.
Embodiment 3: rapid detection kit for screening P16 protein cervical cancer
1. A rapid detection kit based on P16 protein detection is developed, and comprises a pre-packaged reactant and a detection strip.
2. The user collects a cervical cell sample and places the sample in a kit.
3. After waiting for a specific time, the expression of the P16 protein is judged by the color change on the detection strip.
4. And rapidly screening the risk of the lesion before cervical cancer according to the detection result.
The cervical cancer screening device is suitable for basic medical institutions and home self-testing, and provides a quick and convenient solution for cervical cancer screening.
Embodiment 4: p16 protein automatic cervical cancer screening system based on digital image processing
1. Cervical cell samples were collected and P16 protein immunostained.
2. A high resolution digital scanner is used to obtain an image of the stained cell sample.
3. The expression of the P16 protein is automatically analyzed by using image processing software, and the expression comprises color depth and distribution range.
4. And automatically judging the risk level of the lesion before cervical cancer according to the image analysis result.
Is suitable for clinical laboratories with high throughput and improves the efficiency and accuracy of cervical cancer screening.
Two specific application embodiments of the embodiment of the invention are as follows:
example 1: application in routine cervical cancer screening
In conventional cervical cancer screening, cervical transformation zone P16 protein detection is performed for women at high risk for HPV infection. The P16 protein is used as a cell cycle regulatory protein and can be over-expressed when cervical cells are abnormally proliferated due to high-risk HPV infection. The expression condition of the combined P16 protein can be checked by colposcopy, so that the premalignant lesions and early cervical cancer can be identified more accurately.
First, women positive for high-risk HPV are selected for cervical cell sample collection. And detecting the P16 protein in the collected sample, and observing the expression condition of the P16 protein. Cervical lesions are classified in combination with colposcopy results, such as type III, type II or type I lesions. And accurately diagnosing cervical lesions according to P16 protein expression and colposcopy results.
Example 2: screening of cervical cancer high risk population
In screening for cervical cancer high risk populations (e.g., multiple personality partners, early sexual activity, long-term contraceptive users, etc.), P16 protein detection is used as an auxiliary diagnostic tool.
The over-expression of the P16 protein is closely related to cervical cell changes caused by HPV infection, and can be used as an effective index of early cervical cancer and precancerous lesions.
In combination with colposcopy, more comprehensive diagnostic information can be provided, particularly at the early stages of cervical cell changes following HPV infection.
Screening high risk people for cervical cancer screening. And (3) collecting cervical cell samples of the screening objects, and simultaneously detecting high-risk HPV. The samples were tested for P16 protein and their expression levels were observed. And combining with colposcopy results, classifying and diagnosing cervical lesions more accurately. Based on the diagnosis results, corresponding clinical treatment suggestions are provided or further medical interventions are performed.
The invention is mainly aimed at improving the problems and defects of the following prior art, and realizes remarkable technical progress:
Early cervical cancer is difficult to diagnose: traditional cervical cancer screening methods (e.g., relying solely on cervical cytology smears) have limitations in the diagnosis of early cervical cancer and precancerous lesions, especially in high-risk HPV infected individuals.
The diagnosis accuracy is not enough: the traditional method has certain limitation in distinguishing cervical lesions of different degrees, such as insufficient accuracy in distinguishing mild, moderate and high abnormal cell changes.
The screening leakage rate is higher: traditional screening methods miss some early lesions, especially without obvious symptoms.
Aiming at the problems existing in the prior art, the invention adopts the following technical scheme:
Use of P16 protein: p16 protein is used as a biomarker for early cervical cancer and precancerous lesions, and P16 is usually over-expressed in the precancerous lesions.
In connection with colposcopy: by combining cytological P16 detection with colposcopy, the diagnostic accuracy of cervical cancer and precancerous lesions is improved.
Classification of cervical lesions: lesions in cervical transformation regions can be more accurately classified by the expression of the P16 protein, and type III (highly abnormal), type II (moderately abnormal) and type I (slightly abnormal) lesions can be distinguished.
The invention solves the technical effects and remarkable technical progress brought by the prior art problems:
improving early diagnosis rate: the P16 protein is used as a biomarker, and the diagnosis rate of early cervical cancer and precancerous lesions is remarkably improved by combining colposcopy.
Improving the diagnosis accuracy: by combining cytology P16 detection with colposcopy, cervical lesions of different degrees can be distinguished more accurately, and risks of misdiagnosis and missed diagnosis are reduced.
Effective screening for high risk group: the method is particularly suitable for the high-risk HPV infected population, and provides a more effective screening means for the specific population.
As shown in fig. 1, the process of applying P16 in colposcopy to persistent high-risk HPV provided by the embodiment of the present invention includes the following steps:
S101: in the high-risk HPV infected population, cytological P16 detection is carried out on the cervical transformation area, and the microscopic examination result is combined;
s102: classifying cervical lesions; wherein type III lesions refer to highly abnormal cellular changes, while type II lesions refer to moderately abnormal cellular changes, and type I lesions refer to mildly abnormal cellular changes.
In order to realize the application of the P16 protein as an early cervical cancer screening marker, the following is a specific implementation scheme:
Step 1: cervical sample collection
In a female population infected with high-risk HPV, a cell sample is collected from the cervical transformation area by a medical professional using a cervical brush or a cytological smear tool.
Step 2: cytological assays for P16 proteins
Quantitative detection of P16 protein is carried out on the collected cell samples by adopting an immunocytochemistry staining method (IHC). Specifically included are sample fixation, sectioning, staining, and microscopic evaluation to determine P16 protein expression in cells.
Step 3: colposcopy
And (3) carrying out colposcopy on patients with positive P16 protein detection results, and carrying out more accurate evaluation and classification on cervical lesions by magnifying and observing microscopic changes of cervical surfaces and combining the expression condition of the P16 protein.
Step 4: cervical lesion classification
Cervical lesions are classified into three categories based on P16 protein expression levels and colposcopy results: type I (mild abnormal cellular changes), type II (moderate abnormal cellular changes) and type III (highly abnormal cellular changes). This classification helps to determine the strategy for further treatment.
Step5: data recording and analysis
All detection data are recorded in an electronic medical system, statistical analysis is carried out on the data, and the accuracy and the reliability of the P16 protein serving as a marker for pre-cervical cancer lesion and early cervical cancer screening are evaluated.
Step 6: diagnostic and therapeutic advice
Based on the P16 test and colposcopic results, personalized diagnostic and therapeutic advice is provided to the patient. For patients with highly abnormal cellular changes, further diagnostic examinations and treatments are needed.
1. Early diagnosis: the detection of the P16 protein can find abnormal changes of cells in the pre-cervical cancer lesion stage, so that early diagnosis of cervical cancer is realized.
2. High sensitivity: the P16 protein is detected by immunocytochemistry staining method, so that the sensitivity and specificity of diagnosis are improved.
3. Accurate classification: and combining colposcopy, accurately classifying cervical lesions according to P16 protein expression and microscopic change of cervical tissues, and guiding clinical treatment.
4. Individualization treatment: according to classification of cervical lesions, personalized treatment suggestions are provided for patients, and treatment effects are improved.
Through the embodiment, the P16 protein is used as a marker for screening early cervical cancer, so that the early diagnosis rate of cervical cancer can be effectively improved, and the method has important significance for improving female health.
The application of P16 in colposcopy in continuous high-risk HPV cytology P16 detection provided by the embodiment of the invention is a method for judging whether cells are abnormal or not by detecting P16 protein in the cells. The P16 protein is over-expressed in the precancerous lesion, so that the protein can be used as a marker for early cervical cancer screening.
Joint microscopy is a method that combines cytological P16 detection with microscopy. In the high-risk HPV infected population, cervical lesions can be classified by cytological P16 detection of cervical transformation area in combination with microscopic examination. Wherein type III lesions refer to highly abnormal cellular changes, whereas type I lesions are slightly abnormal cellular changes.
Compared with the traditional liquid-based cytology detection, the combined microscopic examination has higher accuracy. Liquid-based cytology can only be used for judging whether the cells are abnormal by observing the cell morphology, and combined microscopy can be used for more accurately judging whether the cells are abnormal by detecting the expression of the P16 protein. Thus, combined microscopy can increase the detection rate of early cervical variations. By applying cytological P16 detection combined microscopy to high-risk HPV infected people, the early stage of cervical lesions can be better screened, and more opportunities for early treatment are provided. This helps to increase the early diagnostic rate of cervical cancer and reduce the morbidity and mortality of cervical cancer. Overall, cytological P16 detection combined with the microscopic examination has higher accuracy in the detection of early cervical variation, can improve the early screening effect of cervical lesions, and provides more accurate guidance for clinical treatment.
The invention applies cytology P16 detection combined colposcopy to high-risk HPV infected people, discusses classification sense under different types (III/II/I type) of cervical transformation areas, evaluates whether the cervical transformation area has higher accuracy rate compared with liquid-based cytology detection, and can further improve the early cervical transformation or detection rate so as to provide more reference basis for popularization and application in vast woman cervical lesion early screening projects, thereby better guiding clinical treatment.
The invention provides a comprehensive system for early screening of cervical cancer, which aims to improve the accuracy of early detection and diagnosis of cervical cancer by accurately collecting and analyzing cell samples of cervical transformation areas of individuals infected by high-risk Human Papillomavirus (HPV). The core composition of the system comprises a sample acquisition unit, a P16 detection unit and an image acquisition unit, and the units work cooperatively, so that not only is accurate acquisition and effective analysis of a sample ensured, but also cervical health status is intuitively displayed through a high-definition image, and powerful support is provided for clinical diagnosis.
At the sample collection unit, a healthcare worker uses specialized tools to obtain a cell sample from the cervical transformation area, which is the first step in the overall screening process. Subsequently, the P16 detection unit analyzes the collected sample to detect the expression level of the P16 protein, so as to identify whether the cells are abnormal. Meanwhile, the image acquisition unit is provided with a colposcope, captures a high-definition image of the cervical transformation area, and provides visual data for a doctor to evaluate cervical tissues.
The data analysis processing unit receives the P16 detection result and the image data, classifies cervical lesions by using an advanced data analysis technology, and identifies type III lesions (highly abnormal cell changes), type II lesions (moderately abnormal cell changes) and type I lesions (slightly abnormal cell changes). And the output display unit displays the classification result and the related images and assists doctors in clinical diagnosis and treatment decision.
In addition, the system also comprises a user interaction unit, a database management unit, a communication interface unit, a quality control evaluation unit and an education training unit, and the units together form a comprehensive, efficient and accurate cervical cancer early screening system. The user interaction unit provides a friendly operation interface, the database management unit is responsible for storing and managing all important data, the communication interface unit ensures seamless connection with an external system, the quality control evaluation unit ensures stability and accuracy of the system, the education and training unit provides precious cervical cancer prevention and treatment knowledge for medical staff and patients, and the efficiency and accuracy of early screening of cervical cancer are greatly improved as a whole.
The foregoing is merely illustrative of specific embodiments of the present invention, and the scope of the invention is not limited thereto, but any modifications, equivalents, improvements and alternatives falling within the spirit and principles of the present invention will be apparent to those skilled in the art within the scope of the present invention.

Claims (9)

CN202410623190.6A2024-05-202024-05-20Application of P16 and colposcopy in persistent high-risk HPVPendingCN118549652A (en)

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