1.A study on the correlation between HPV DNA and IHC P16 expression in cervical lesions
Haochen WANG ; Liqing JIA ; Yu YANG ; Qian WANG ; Chengli YU ; Tian TIAN ; Rui BI ; Xiaoyu TU ; Qianming BAI ; Xiaoli ZHU ; Xiaoyan ZHOU ; Min REN
China Oncology 2025;35(3):298-308
Background and purpose:Human papilloma virus(HPV)infection status is crucial for diagnosing cervical precancerous lesions and classifying cervical cancer.High-risk(HR)HPV is often linked to P16 protein overexpression,so P16 detection via immunohistochemistry(IHC)is commonly used to assess HPV infection.However,the differences between HPV status and P16 expression remains unclear.An in-depth study of the correlation between HPV and P16 is essential for clinical guidance.Methods:We retrospectively collected clinical and pathological data of cervical lesions from 618 patients diagnosed at the Department of Pathology,Fudan University Shanghai Cancer Center from January 2020 to December 2023(Ethical number:050432-4-2307E).Polymerase chain reaction(PCR)reverse dot hybridization was used to detect HPV including HR and low-risk(LR)subtypes,and immunohistochemistry was used to detect P16 for comparative analysis.Based on different clinical and pathological diagnoses,the sensitivity and specificity of P16 expression in evaluating HPV infection were evaluated.Among the 618 cases of cervical lesions,there were 92 cases of cervical squamous cell carcinoma,257 cases of cervical adenocarcinoma,79 cases of high-grade squamous intraepithelial lesions(HSIL),105 cases of low-grade squamous intraepithelial lesions(LSIL),and 85 cases of chronic cervical inflammation.Results:According to clinical diagnosis,the HR-HPV positive rate in cervical squamous cell carcinoma was 88.0%(81/92),the P16 positive rate was 91.3%(84/92),and the overall consistency rate between P16 and HPV detection was 90.2%(88/92);for HR-HPV infection,the sensitivity and specificity of P16 were 96.3%and 45.5%.The positive rate of HR-HPV in adenocarcinoma was 54.5%(140/257),the positive rate of P16 was 58.8%(151/257),and the overall consistency rate between P16 and HPV detection was 82.5%(212/257);for HR-HPV infection,the sensitivity and specificity of P16 were 87.9%and 76.1%.In HSIL,the HR-HPV positive rate was 75.9%(60/79),the positive rate of P16 was 70.9%(56/79),and the overall consistency rate between P16 and HR-HPV detection was 82.2%(65/79);for HR-HPV infection,the sensitivity and specificity of P16 were 85.0%and 73.7%.In LSIL,the HR-HPV positive rate was 73.3%(77/105),the positive rate of P16 was 8.5%(9/105),and the overall consistency rate between P16 and HR-HPV detection was 33.3%(35/105);for HR-HPV infection,the sensitivity and specificity of P16 were 10.4%and 96.4%.In chronic cervical inflammation,the HR-HPV positive rate was 20%(17/85),the positive rate of P16 was 0.0%(0/85);for HR-HPV infection,the sensitivity and specificity of P16 were 0.0%and 100.0%.There was a significant positive correlation between P16 positivity and HPV16/18 in cervical squamous cell carcinoma,adenocarcinoma,and HSIL(P=0.000),while there was no significant correlation in LSIL and chronic cervical inflammation(P>0.05).Conclusion:In cervical squamous cell carcinoma and adenocarcinoma,the consistency of P16 expression and HPV DNA positivity are high,especially in HPV16/18 subtype.There is a good concordance between HR-HPV positivity and P16 protein overexpression.The positive expression of P16 in HSIL may initially reflect HPV infection status.However,in LSIL and chronic cervicitis,P16 expression may not accurately correlate with HPV infection.The inconsistency between P16 and HPV DNA testing could be influenced by multiple factors,including HPV subtypes,histopathological categories,specimen quality,and technical limitations.In clinical practice,it is recommended to conduct comprehensive analysis or employ multiple diagnostic methods to confirm HPV infection status for precise evaluation.
2.A study on the correlation between HPV DNA and IHC P16 expression in cervical lesions
Haochen WANG ; Liqing JIA ; Yu YANG ; Qian WANG ; Chengli YU ; Tian TIAN ; Rui BI ; Xiaoyu TU ; Qianming BAI ; Xiaoli ZHU ; Xiaoyan ZHOU ; Min REN
China Oncology 2025;35(3):298-308
Background and purpose:Human papilloma virus(HPV)infection status is crucial for diagnosing cervical precancerous lesions and classifying cervical cancer.High-risk(HR)HPV is often linked to P16 protein overexpression,so P16 detection via immunohistochemistry(IHC)is commonly used to assess HPV infection.However,the differences between HPV status and P16 expression remains unclear.An in-depth study of the correlation between HPV and P16 is essential for clinical guidance.Methods:We retrospectively collected clinical and pathological data of cervical lesions from 618 patients diagnosed at the Department of Pathology,Fudan University Shanghai Cancer Center from January 2020 to December 2023(Ethical number:050432-4-2307E).Polymerase chain reaction(PCR)reverse dot hybridization was used to detect HPV including HR and low-risk(LR)subtypes,and immunohistochemistry was used to detect P16 for comparative analysis.Based on different clinical and pathological diagnoses,the sensitivity and specificity of P16 expression in evaluating HPV infection were evaluated.Among the 618 cases of cervical lesions,there were 92 cases of cervical squamous cell carcinoma,257 cases of cervical adenocarcinoma,79 cases of high-grade squamous intraepithelial lesions(HSIL),105 cases of low-grade squamous intraepithelial lesions(LSIL),and 85 cases of chronic cervical inflammation.Results:According to clinical diagnosis,the HR-HPV positive rate in cervical squamous cell carcinoma was 88.0%(81/92),the P16 positive rate was 91.3%(84/92),and the overall consistency rate between P16 and HPV detection was 90.2%(88/92);for HR-HPV infection,the sensitivity and specificity of P16 were 96.3%and 45.5%.The positive rate of HR-HPV in adenocarcinoma was 54.5%(140/257),the positive rate of P16 was 58.8%(151/257),and the overall consistency rate between P16 and HPV detection was 82.5%(212/257);for HR-HPV infection,the sensitivity and specificity of P16 were 87.9%and 76.1%.In HSIL,the HR-HPV positive rate was 75.9%(60/79),the positive rate of P16 was 70.9%(56/79),and the overall consistency rate between P16 and HR-HPV detection was 82.2%(65/79);for HR-HPV infection,the sensitivity and specificity of P16 were 85.0%and 73.7%.In LSIL,the HR-HPV positive rate was 73.3%(77/105),the positive rate of P16 was 8.5%(9/105),and the overall consistency rate between P16 and HR-HPV detection was 33.3%(35/105);for HR-HPV infection,the sensitivity and specificity of P16 were 10.4%and 96.4%.In chronic cervical inflammation,the HR-HPV positive rate was 20%(17/85),the positive rate of P16 was 0.0%(0/85);for HR-HPV infection,the sensitivity and specificity of P16 were 0.0%and 100.0%.There was a significant positive correlation between P16 positivity and HPV16/18 in cervical squamous cell carcinoma,adenocarcinoma,and HSIL(P=0.000),while there was no significant correlation in LSIL and chronic cervical inflammation(P>0.05).Conclusion:In cervical squamous cell carcinoma and adenocarcinoma,the consistency of P16 expression and HPV DNA positivity are high,especially in HPV16/18 subtype.There is a good concordance between HR-HPV positivity and P16 protein overexpression.The positive expression of P16 in HSIL may initially reflect HPV infection status.However,in LSIL and chronic cervicitis,P16 expression may not accurately correlate with HPV infection.The inconsistency between P16 and HPV DNA testing could be influenced by multiple factors,including HPV subtypes,histopathological categories,specimen quality,and technical limitations.In clinical practice,it is recommended to conduct comprehensive analysis or employ multiple diagnostic methods to confirm HPV infection status for precise evaluation.
3.Comparison of fluorescence in situ hybridization(FISH)and urine cytology in diagnosing urothelial carcinoma:a single-center retrospective cohort study
Zhiting WANG ; Min REN ; Tian XUE ; Haochen WANG ; Heng CHANG ; Qianming BAI ; Xiaoyan ZHOU ; Xiaoli ZHU
China Oncology 2024;34(12):1080-1089
Background and purpose:Urothelial carcinoma(UC)is a prevalent malignant tumor of the urinary system,and early diagnosis is crucial for improving patient prognosis.This study evaluated the diagnostic efficacy of fluorescence in situ hybridization(FISH),urine cytology and their combination for UC,as well as for its different subtypes.Methods:This study included patients who underwent transurethral resection of bladder tumor(TURBT)from January 2022 to December 2023 and approved by Ethics Commetce of Fudan Univesity Shanghai Cancer Center,No.:050432-4-2307E)that met the inclusion and exclusion criteria.We collected TURBT pathological results and pre-procedure FISH and cytology results.Diagnostic accuracy,sensitivity and specificity of FISH,cytology and their combination were analyzed and compared for urothelial carcinoma.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist and Standards for Reporting of Diagnostic Accuracy(STARD)were followed for this study.Results:A total of 283 patients were enrolled in this study,136 were diagnosed with UC,and 147 were not.Of the 136 UC cases,79(58.09%)were invasive and 57(41.91%)were non-invasive.In terms of malignancy grade,112(82.35%)were high-grade UC and 24(17.65%)were low-grade UC.Using histopathology as the gold standard,the accuracy of FISH,cytology and their combination in diagnosing UC was 79.51%,72.08%and 77.39%,respectively;sensitivity was 72.06%,58.82%and 78.68%,respectively;specificity was 86.39%,84.35%and 76.19%,respectively.The area under the curve(AUC)for FISH and the combination was similar but higher than that for cytology(0.792 vs 0.716,P=0.006;0.774 vs 0.716,P=0.004);the Net Reclassification Improvement(NRI)for FISH compared to cytology was 15.28%(P=0.006).In the 79 cases of invasive UC,FISH had higher accuracy than cytology(86.28%vs 78.32%,P=0.011).The sensitivity of FISH and the combination was higher than that of cytology(86.08%vs 67.09%,P=0.004;91.14%vs 67.09%,P<0.001),and the AUC values were also higher(0.808 vs 0.713,P=0.004;0.784 vs 0.713,P=0.007).The NRI for FISH compared to cytology was 21.03%(P=0.003).In the 57 cases of non-invasive UC,the AUC values for all three methods were low(AUC<0.700).Among the 112 cases of high-grade UC,FISH had higher accuracy(84.94%vs 76.45%,P=0.005),and the combination had higher sensitivity(89.29%vs 66.07%,P<0.001)compared to cytology.The AUC values for FISH and the combination were also superior to that for cytology(0.847 vs 0.752,P=0.002;0.827 vs 0.752,P=0.001).The NRI for FISH compared to cytology was 19.01%(P=0.003).In the 24 cases of low-grade UC,the AUC values for all three methods were low(AUC<0.600).Conclusion:For UC,particularly invasive and high-grade subtypes,FISH shows superior diagnostic efficacy compared to cytology.FISH alone offers accuracy and sensitivity comparable to the combination test,with higher specificity.In cases of non-invasive or low-grade UC,however,all three diagnostic methods demonstrate relatively low efficacy.
4.Comparison of fluorescence in situ hybridization(FISH)and urine cytology in diagnosing urothelial carcinoma:a single-center retrospective cohort study
Zhiting WANG ; Min REN ; Tian XUE ; Haochen WANG ; Heng CHANG ; Qianming BAI ; Xiaoyan ZHOU ; Xiaoli ZHU
China Oncology 2024;34(12):1080-1089
Background and purpose:Urothelial carcinoma(UC)is a prevalent malignant tumor of the urinary system,and early diagnosis is crucial for improving patient prognosis.This study evaluated the diagnostic efficacy of fluorescence in situ hybridization(FISH),urine cytology and their combination for UC,as well as for its different subtypes.Methods:This study included patients who underwent transurethral resection of bladder tumor(TURBT)from January 2022 to December 2023 and approved by Ethics Commetce of Fudan Univesity Shanghai Cancer Center,No.:050432-4-2307E)that met the inclusion and exclusion criteria.We collected TURBT pathological results and pre-procedure FISH and cytology results.Diagnostic accuracy,sensitivity and specificity of FISH,cytology and their combination were analyzed and compared for urothelial carcinoma.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist and Standards for Reporting of Diagnostic Accuracy(STARD)were followed for this study.Results:A total of 283 patients were enrolled in this study,136 were diagnosed with UC,and 147 were not.Of the 136 UC cases,79(58.09%)were invasive and 57(41.91%)were non-invasive.In terms of malignancy grade,112(82.35%)were high-grade UC and 24(17.65%)were low-grade UC.Using histopathology as the gold standard,the accuracy of FISH,cytology and their combination in diagnosing UC was 79.51%,72.08%and 77.39%,respectively;sensitivity was 72.06%,58.82%and 78.68%,respectively;specificity was 86.39%,84.35%and 76.19%,respectively.The area under the curve(AUC)for FISH and the combination was similar but higher than that for cytology(0.792 vs 0.716,P=0.006;0.774 vs 0.716,P=0.004);the Net Reclassification Improvement(NRI)for FISH compared to cytology was 15.28%(P=0.006).In the 79 cases of invasive UC,FISH had higher accuracy than cytology(86.28%vs 78.32%,P=0.011).The sensitivity of FISH and the combination was higher than that of cytology(86.08%vs 67.09%,P=0.004;91.14%vs 67.09%,P<0.001),and the AUC values were also higher(0.808 vs 0.713,P=0.004;0.784 vs 0.713,P=0.007).The NRI for FISH compared to cytology was 21.03%(P=0.003).In the 57 cases of non-invasive UC,the AUC values for all three methods were low(AUC<0.700).Among the 112 cases of high-grade UC,FISH had higher accuracy(84.94%vs 76.45%,P=0.005),and the combination had higher sensitivity(89.29%vs 66.07%,P<0.001)compared to cytology.The AUC values for FISH and the combination were also superior to that for cytology(0.847 vs 0.752,P=0.002;0.827 vs 0.752,P=0.001).The NRI for FISH compared to cytology was 19.01%(P=0.003).In the 24 cases of low-grade UC,the AUC values for all three methods were low(AUC<0.600).Conclusion:For UC,particularly invasive and high-grade subtypes,FISH shows superior diagnostic efficacy compared to cytology.FISH alone offers accuracy and sensitivity comparable to the combination test,with higher specificity.In cases of non-invasive or low-grade UC,however,all three diagnostic methods demonstrate relatively low efficacy.
5.Unconstrained detection of ballistocardiogram and heart rate based on vibration acceleration.
Haochen TIAN ; Haiwen ZHAO ; Shijie GUO ; Jinyue LIU ; Xuzhi WANG
Journal of Biomedical Engineering 2019;36(2):281-290
The requirement for unconstrained monitoring of heartbeat during sleep is increasing, but the current detection devices can not meet the requirements of convenience and accuracy. This study designed an unconstrained ballistocardiogram (BCG) detection system using acceleration sensor and developed a heart rate extraction algorithm. BCG is a directional signal which is stronger and less affected by respiratory movements along spine direction than in other directions. In order to measure the BCG signal along spine direction during sleep, a 3-axis acceleration sensor was fixed on the bed to collect the vibration signals caused by heartbeat. An approximate frequency range was firstly assumed by frequency analysis to the BCG signals and segmental filtering was conducted to the original vibration signals within the frequency range. Secondly, to identify the true BCG waveform, the accurate frequency band was obtained by comparison with the theoretical waveform. The J waves were detected by BCG energy waveform and an adaptive threshold method was proposed to extract heart rates by using the information of both amplitude and period. The accuracy and robustness of the BCG detection system proposed and the algorithm developed in this study were confirmed by comparison with electrocardiogram (ECG). The test results of 30 subjects showed a high average accuracy of 99.21% to demonstrate the feasibility of the unconstrained BCG detection method based on vibration acceleration.
Acceleration
;
Ballistocardiography
;
Electrocardiography
;
Heart Rate
;
Humans
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Signal Processing, Computer-Assisted
;
Vibration
6.Clinical Research on Bushen Huoxue Prescription in Treating Kidney Deficiency and Blood Stasis Type Primary Osteoporosis
Lin TIAN ; Haochen KANG ; Shuli WANG ; Ge YANG ; Jiangui ZHU
Chinese Journal of Information on Traditional Chinese Medicine 2017;24(9):11-14
Objective To observe the efficacy and safety of Bushen Huoxue Prescription in the treatment of kidney deficiency and blood stasis type primary osteoporosis. Methods Totally 50 patients with kidney deficiency and blood stasis type primary osteoporosis were collected. They were given Bushen Huoxue Prescription granules twice a day, taking with water, for 12 weeks. Before and after treatment, the femoral neck, Ward's area, L1–4 bone mineral density (BMD) were measured. VAS and TCM syndrome integrals were evaluated before and 4, 8 and 12 week of treatment. The level of serum osteocalcin (OC), β-C-terminal telopeptides of type I collagen (β-CTX) and osteoprotegerin (OPG) were detected before and after treatment. Hematuria routine, liver and kidney function were under safety testing before and after treatment. Results Bushen Huoxue Prescription could significantly increase BMD of left femoral neck and Ward's triangle (P=0.001, P=0.044). L1–4 BMD increased, without statistical significance (P=0.172). The total effective rate was 60.870% (28/46) for L1–4 and left femoral neck and 58.696% (27/46) for Ward's triangle. The VAS and TCM syndrome integral decreased significantly 4 weeks treatment compared with that before the treatment (P<0.01), and the scores decreased significantly with the prolongation of treatment time (F=159.690, P<0.001; F=163.970, P<0.001). After 12 weeks, treatment, the total effective rate for TCM syndromes was 78.26% (36/46). Serum levels of OC and β-CTX showed a tendency to increase, while serum levels of OPG showed a tendency to decrease, without statistical significance (P=0.087, P=0.091, P=0.419). There was no serious adverse reaction in hematuria routine and liver and kidney function. Conclusion Bushen Huoxue Prescription has obvious clinical efficacy for kidney deficiency and blood stasis type primary osteoporosis, which can improve the patients' BMD, improve bone metabolism, relive bone pain, with high level of safety.

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