Clinical significance of human papillomavirus 16/18 E6 protein detection in shunting and prognosis of patients with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions / 肿瘤研究与临床

Objective To evaluate the value of human papillomavirus (HPV) 16/18 E6 protein detection in shunting and prognosis in patients with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL). Methods A total of 98 patients with ASCUS or LSIL from the Affiliated Cancer Hospital of Shanxi Medical University between May 2014 and May 2015 were selected as the subjects. All of them received the thin-cytologic test (TCT), HPV DNA, HPV16/18 E6 protein tests and colposcopy examination. After 3-year follow-up of patients with cervical intraepithelial neoplasia (CIN) grade Ⅰor bellow lesions diagnosed by biopsy and 30 negative controls, the above tests were performed again. The efficacies of all the tests were analyzed. The value of CIN grade Ⅱ or above was predicted. Results The sensitivity, specificity, positive predictive value and negative predictive value in predicting CIN grade Ⅱor above lesions of HPV16/18 E6 protein , HPV DNA and HPV16/18 DNA was 30.8％, 95.3％, 50.0％, 90.0％, respectively; 84.6％, 37.6％, 17.2％, 94.1％, respectively and 61.5％, 67.1％, 22.2％, 91.9％, respectively in shunting study. The relative risk (RR) of CIN grade Ⅱor above lesions in patients with positive HPV16/18 E6 protein, persistent positive HPV16/18 DNA and positive HPV16/18 DNA was 13.429, 10.231 and 8.343, respectively in the follow-up study. Odds ratio (OR) of HPV16/18 E6 positive protein presenting persistent positive HPV16/18 DNA was 34.833 (95％ CI 5.020-241.711). Conclusions In patients with ASCUS and LSIL, the specificity and positive predictive value of HPV16/18 E6 protein in predicting CIN grade Ⅱ or above lesions are higher than those of HPV DNA and HPV16/18 DNA. Moreover, these patients with HPV16/18 E6 protein positive have a higher risk of developing CIN grade Ⅱ or above lesions and persistent positive HPV16/18 DNA.

Clinical value of p16 and geminin in the progress of patients with low?grade squamous intraepithelial lesions / 中国综合临床

Objective To analyze the positive expression levels of p16 ( p16ink4a), cell cycle factor geminin and Ki-67 in low-grade squamous intraepithelial lesions ( LSIL),and to further explore the ability of these indicators to evaluate the progression of LSIL patients. Methods From January 2015 to June 2018,276 cervical specimens from Jiading District Central Hospital of Shanghai were retrospectively studied, and 148 LSIL patients were selected. According to the results of the second examination,LSIL patients were divided into three groups: (1) no lesion (natural regression) group 90 cases; (2) LSIL persistent group 38 cases; (3) high-grade Squamous Intraepithelial Lesion (HSIL) group 20 cases. Immunohistochemistry was performed on the first biopsy tissues and the relative positive ratios of p16, geminin and Ki-67 were calculated. Spearman correlation analysis identified the correlation between the above indicators and the progress of the disease; ROC curve was used to calculate the best diagnostic value of each indicator,and multivariate logistic regression analysis was included to explore the ability of the above indicators to assess the risk of patients progressing to HSIL. Results In the HSIL group, p16 ( 51. 26 ± 17. 15)%, geminin relative positive ratio ( 45. 92 ± 15. 70)% was higher than those in the LSIL group(( 43. 71 ± 11. 84)%, (21. 68± 14. 47)%) and regression group (( 17. 92 ± 9. 60)%, ( 0. 16 ± 0. 03)%) . The difference were statistically significant ( F＝2. 922, 2. 751, all P＜0. 05) . Spearman correlation analysis showed that the relative positive ratio of p16 ( r＝0. 27,P＝0. 014) and geminin ( r＝0. 44,P＜0. 001) presented a notable positive correlation with the progression of the disease. Under the ROC curve,the best diagnostic values of p16, geminin and Ki-67 were 38. 9%, 32. 5% and 18. 6%, respectively. Multivariate logistic regression analysis showed that the relative positive ratio of p16 was higher than 38. 9%(OR＝4. 366,P＝0. 006),and geminin was higher than 32. 5%( OR ＝ 5. 392, P ＝ 0. 011 ) had a higher risk of progression to HSIL. Conclusion p16 and geminin may be effective biomarkers for identifying patients with advanced LSIL.

Evolución de las lesiones escamosas intraepiteliales de bajo grado del cérvix (2012-2013) / Evolution of Cervix Low-Grade Squamous Intraepithelial Lesions (2012-2013)

Introducción: las lesiones intraepiteliales cervicales son precursoras del cáncer de cuello uterino, enfermedad que causó 465 muertes en Cuba en el año 2015. Objetivo: describir la evolución de las lesiones intraepiteliales de bajo grado del cérvix durante un bienio según lo dispuesto en el Programa Nacional de Diagnóstico Precoz del Cáncer Cervicouterino. Métodos: se realizó un estudio descriptivo, longitudinal y prospectivo a 79 pacientes diagnosticadas citológicamente con una lesión escamosa intraepitelial de bajo grado en el período comprendido entre el 1ro de septiembre de 2012 y el 31 de agosto de 2013 en el Hospital Materno Ramón González Coro. Seguimiento evolutivo cada seis meses durante dos años. Resultados: 54,4 por ciento tenía entre 25 y 39 años de edad. Del total, 65,8 por ciento negativizó la citología entre los 6 y 18 meses. En los dos años de evolución, 25,3 por ciento del total progresó a una lesión de alto grado. Existió buena correlación citocolposcópica en 80 por ciento de las pacientes. El cálculo de la mediana de la zona transformación atípica en las lesiones de alto grado fue de 25 por ciento, muy superior a las de bajo grado. Hubo confirmación histológica en todos los casos cuya lesión progresó. Conclusiones: las pacientes que negativizaron la citología lo hizo durante los 18 meses de seguimiento. Existió buena relación citohistológica, no así colpohistológica. La evolución no guardó relación con las variables sociodemográficas excepto con el uso de DIU. Lesiones que ocupan más del 20 por ciento de la zona de transformación se relacionó con progresión hacia una lesión escamosa intraepitelial de alto grado(AU)

Introduction: Cervical intraepithelial lesions are signs of cervical cancer, a disease that caused 465 deaths in Cuba in 2015. Objective: To describe the evolution of low-grade intraepithelial lesions of the cervix during a biennium according to the provisions of the National Program of Early Diagnosis of Cervical Cancer. Methods: A descriptive, longitudinal and prospective study was carried out on 79 patients diagnosed by cytology with a low-grade squamous intraepithelial lesion from September 1, 2012 to August 31, 2013 at Ramón González Coro Gyneco-Obstetric Hospital. These subjects received an evolutionary follow-up every six months for two years. Results: 54.4 percent were between 25 and 39 years of age; 65.8 percent had negative cytology between 6 and 18 months. In the two years of evolution, 25.3 percent of the total progressed to a high-grade lesion. There was good cytocolposcopic correlation in 80 percent of the patients. The calculation of the median of the atypical transformation zone in the high-grade lesions was 25 percent, much higher than the low-grade ones. There was histological confirmation in all cases whose lesion progressed. Conclusions: Negative cytology in our patients was assessed during the 18 months of follow-up period. There was good cytohistological relationship, but not so for colpohistological relationship. The evolution was not related to the sociodemographic variables except with the use of IUD. Lesions that occupy more than 20 percent of the transformation zone were associated with progression towards a high-grade squamous intraepithelial lesion(AU)

Relationship between low-grade squamous intraepithelial lesions and high risk human papillomavirus / 临床与实验病理学杂志

Purpose To study the infection mode and distribution of high risk human papillomavirus (HR-HPV) in lowgrade squamous intraepithelial lesions (LSILs) and to analysis its effect.Methods HPV genotype of 328 cervical tissues embedded by paraffin which contained 168 LSILs and 160 highgrade squamous intraepithelial lesions (HSILs) were detected by the methods of real-time fluorescence quantitative PCR and in situ hybridization.Results Diseased cells of LSIL stained with hematoxylin and eosin(HE) were concentrated in the upper layer of the cervical squamous epithelium,whereas HSIL were concentrated in the lower layer of the epithelium in HE staining.In LSIL,the positive ratcs of HR-HPV was 95.2％.In LSIL and HSIL,HPV 16/18 positive rates were 26.2％,57.5％,respectively.Other HR-HPV positive rates were 80.9％,55.0％,respectively.The differences were statistically significant (P ＜0.001).HR-HPV positive rate was 70.2％ in the group of in situ hybridization.The positive cells were confined to the surface and middle layer of the LSIL cervical squamous epithelium.Conclusion HR-HPV infection is closely related to LSIL,especially other HR-HPV (except for HPV 16/18).The infection mode of HR-HPV in LSIL starts from the surface layer of the cervical squamous epithelium.

Atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion triage in Korean women: Revisiting the 2012 American Society of Colposcopy and Cervical Pathology screening guidelines

OBJECTIVE: To determine whether triage for atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) from the updated American Society for Colposcopy and Cervical Pathology cervical cancer screening guidelines is applicable in Korean women. METHODS: We investigated women with ASC-US or LSIL including referred from local hospitals visited for cervical cancer screening at Korea University Guro Hospital from February 2004 to December 2014. Detailed information on the results of Papanicolaou (Pap) smears, human papillomavirus (HPV) DNA tests, and cervical biopsies were collected through chart review. Cervical biopsy results were compared in eligible women according to individual Pap smear findings and HPV DNA status. RESULTS: Of 216,723 possible cases, 3,196 were included. There were 212 (6.6%) women with ASC-US and 500 (15.6%) with LSIL. The risk of ≥cervical intraepithelial neoplasia (CIN) 2 was significantly higher in women who were ASC-US/HPV+ than ASC-US/HPV- and LSIL/HPV+ than LSIL/HPV- (93.3% vs. 6.7% and 96.7% vs. 3.3%, P<0.001 and P<0.001, respectively). The risk of ≥CIN 3 was also significantly higher in women who were ASC-US/HPV+ than ASC-US/HPV- and LSIL/HPV+ than LSIL/HPV- (97.0% vs. 3.0% and 93.0% vs. 7.0%, P<0.001 and P<0.001, respectively). Age-stratified analysis revealed that more CIN 2 or CIN 3 was diagnosed in women aged 30 to 70 with ASC-US or LSIL when HPV DNA was present. CONCLUSION: Observation with Pap and HPV DNA tests rather than immediate colposcopy is a reasonable strategy for ASC-US or LSIL when the HPV DNA test is negative, especially in women aged 30 to 70. Reflection of these results should be considered in future Korean screening guidelines.

Visual inspection with acetic acid for detection of high grade lesion in atypical squamous cells and low grade squamous intraepithelial lesions from cervical Pap smear / 부인종양

OBJECTIVE: To evaluate the value of visual inspection with acetic acid (VIA) test to detect high grade lesion in women with atypical squamous cells or low grade squamous intraepithelial lesions cervical cytology. METHODS: Women with atypical squamous cells or low grade squamous intraepithelial lesions who were scheduled to undergo colposcopy at Vajira Hospital and met inclusion criteria were included. All participants underwent VIA test prior to usual steps of colposcopy. The VIA results were interpreted as positive or negative using the criteria by the International Agency for Cancer Research. The standard colposcopic examination and appropriate investigations for cervical pathology were then continued. The diagnostic values of VIA test including sensitivity, specificity, positive predictive value, and negative predictive value were determined using high grade lesion including cervical intraepithelial neoplasia 2-3 and squamous cell carcinoma as a threshold. RESULTS: Total of 106 women was included. The VIA test was positive in 33 women (31.1%) and negative in 73 women (68.9%). Among the women with VIA test positive, 14 had high grade lesion (42.4%) while 19 had no significant lesions. Only 2/73 (2.7%) cases with negative VIA test had high grade lesion (both had cervical intraepithelial neoplasia 2). The sensitivity, specificity, positive predictive value and negative predictive value with 95% confidence interval were 87.5% (81.2 to 93.8%), 78.8% (71.1 to 86.7%), 42.4% (33.0 to 51.8%), and 97.2% (94.2 to 1.0%) respectively. CONCLUSION: VIA as the intermediate test in atypical squamous cells and low grade squamous intraepithelial lesions cytology may reduce the necessity to refer some women for colposcopy.

Clinical Significance of HPV DNA test for Management of Patients with Diagnosis of Atypical Squamous Cells of Undetermined Significance/Low-grade Squamous Intraepithelial Lesions / 대한산부인과학회잡지

OBJECTIVE: This study was performed to evaluate the clinical efficacy of high risk HPV DNA test using PCR for the detection of high-grade CIN or invasive cancer from patients with ASCUS or LSIL on Papanicolaou smear. METHODS: Sixty one patients with a Papanicolaou smear report of atypical squamous cells of undetermined significance or a low-grade squamous intraepithelial lesion underwent Cervical colposcopy and directed cervical biopsy and human papillomavirus test by PCR. We compared the detection rate of the high grade CIN and invasive cancer by Papanicolaou smear method only with that of both Papanicolaou smear and HPV PCR method. and we decided to be significant when P value was below 0.05 by SAS (v 6.02) program. RESULTS: The detection rate of high risk HPV DNA was 50.8% (31/61). The detection rate of high risk HPV DNA in high grade CIN and invasive cancer was 84.2% (16/19). Higher the grade of biopsy, more the detection rate of high risk HPV DNA. False negative rate which appeared high grade CIN or invasive cancer by biopsy was 31.2% (19/61) in Papanicolaou smear method only and 4.9% (3/61) in both Papanicolaou smear and HPV DNA method. CONCLUSION: We thought that additional HPV DNA test was useful to dectect behind high grade CIN or invasive cancer when the Papanicolaou smear result was ASCUS or LSIL.