scholarly journals The value of p16INK4a immunostaining for high-grade squamous intraepithelial lesions in human papillomavirus–negative patients

2020 ◽  
Author(s):  
Dai Zhang ◽  
Jie Song ◽  
Xiaosong Zhang ◽  
Hui Bi
Keyword(s):  
Human Papillomavirus ◽  
Predictive Value ◽  
Intraepithelial Neoplasia ◽  
Pathological Diagnosis ◽  
High Grade ◽  
Squamous Intraepithelial Lesions ◽  
P16 Ink4a ◽  
Objective Detection ◽  
High Risk Hpv ◽  
Intraepithelial Lesions

Abstract Background : This study aims to evaluate the value of p16 INK4a immunostaining for high-grade squamous intraepithelial lesions in human papillomavirus–negative patients in Beijing, China. Methods: In this study, we evaluated the value of p16 INK4a immunostaining, as well as cytology and colposcopy, for predicting high-grade squamous intraepithelial lesions (HSIL) in human papillomavirus (HPV)-negative patients by comparing the methods with the haematoxylin and eosin (H&E) staining pathological diagnosis of HPV-negative patients. Results: Of 122 patients negative for the high-risk HPV (HR-HPV) subtype, 26 (21.3%) underwent colposcopically directed multiple punch cervical biopsy with a H&E pathological diagnosis of HSIL and above (HSIL+), 11 patients (9.0%) had cervical intraepithelial neoplasia (CIN)2, nine patients (7.4%) had CIN3, and six patients (4.9%) had infiltrating carcinoma. Cytology, colposcopy, and p16 INK4a immunostaining had 52.4%, 38.5%, and 92.3% sensitivity, respectively, and 76.2%, 94.8%, and 99% specificity, respectively. The positive predictive value of cytology, colposcopy, and p16 INK4a immunostaining was 31.4%, 66.7%, and 96%, respectively, and the negative predictive value was 88.5%, 85.1%, and 97.9%, respectively. Compared with H&E staining, the kappa of cytology, colposcopy, and p16 INK4a immunostaining was 0.327, 0.323, and 0.926, respectively. Conclusion: Positive p16 INK4a immunostaining is very strongly consistent with an H&E diagnosis of CIN2+, and it can be used as an objective detection index for HSIL+ diagnosis of HPV-negative patients with CIN2+.

scholarly journals The Value of p16INK4a Immunostaining for High-grade Squamous Intraepithelial Lesions in Human Papillomavirus–Negative Patients

2020 ◽  
Author(s):  
Dai Zhang ◽  
Jie Song ◽  
Xiaosong Zhang ◽  
Hui Bi
Keyword(s):  
Human Papillomavirus ◽  
Predictive Value ◽  
Intraepithelial Neoplasia ◽  
Pathological Diagnosis ◽  
High Grade ◽  
Squamous Intraepithelial Lesions ◽  
Objective Detection ◽  
High Risk Hpv ◽  
Intraepithelial Lesions ◽  
Beijing China

Abstract Objective This study aims to evaluate the value of p16INK4a immunostaining for high-grade squamous intraepithelial lesions in human papillomavirus–negative patients in Beijing, China.Methods In this study, we evaluated the value of p16INK4a immunostaining, as well as cytology and colposcopy, for predicting high-grade squamous intraepithelial lesions (HSIL) in human papillomavirus (HPV)-negative patients by comparing the methods with the haematoxylin and eosin (H&E) staining pathological diagnosis of HPV-negative patients.Results Of 122 patients negative for the high-risk HPV (HR-HPV) subtype, 26 (21.3%) underwent colposcopically directed multiple punch cervical biopsy with a H&E pathological diagnosis of HSIL and above (HSIL+), 11 patients (9.0%) had cervical intraepithelial neoplasia (CIN)2, nine patients (7.4%) had CIN3, and six patients (4.9%) had infiltrating carcinoma. Cytology, colposcopy, and p16INK4a immunostaining had 52.4%, 38.5%, and 92.3% sensitivity, respectively, and 76.2%, 94.8%, and 99% specificity, respectively. The positive predictive value of cytology, colposcopy, and p16INK4a immunostaining was 31.4%, 66.7%, and 96%, respectively, and the negative predictive value was 88.5%, 85.1%, and 97.9%, respectively. Compared with H&E staining, the kappa of cytology, colposcopy, and p16INK4a immunostaining was 0.327, 0.323, and 0.926, respectively.Conclusion Positive p16INK4a immunostaining is very strongly consistent with an H&E diagnosis of CIN2+, and it can be used as an objective detection index for HSIL + diagnosis of HPV-negative patients.

scholarly journals The value of p16INK4a immunostaining for high-grade squamous intraepithelial lesions in human papillomavirus–negative patients

2021 ◽  
Author(s):  
Dai Zhang ◽  
Jie Song ◽  
Xiaosong Zhang ◽  
Hui Bi
Keyword(s):  
Human Papillomavirus ◽  
Predictive Value ◽  
Intraepithelial Neoplasia ◽  
Pathological Diagnosis ◽  
High Grade ◽  
Squamous Intraepithelial Lesions ◽  
Objective Detection ◽  
High Risk Hpv ◽  
Intraepithelial Lesions ◽  
Beijing China

Abstract Background: This study aims to evaluate the value of p16INK4a immunostaining for high-grade squamous intraepithelial lesions in human papillomavirus–negative patients in Beijing, China. Methods: In this study, we evaluated the value of p16INK4a immunostaining, as well as cytology and colposcopy, for predicting high-grade squamous intraepithelial lesions (HSIL) in human papillomavirus (HPV)-negative patients by comparing the methods with the haematoxylin and eosin (H&E) staining pathological diagnosis of HPV-negative patients. Results: Of 122 patients negative for the high-risk HPV (HR-HPV) subtype, 26 (21.3%) underwent colposcopically directed multiple punch cervical biopsy with a H&E pathological diagnosis of HSIL and above (HSIL+), 11 patients (9.0%) had cervical intraepithelial neoplasia (CIN)2, nine patients (7.4%) had CIN3, and six patients (4.9%) had infiltrating carcinoma. Cytology, colposcopy, and p16INK4a immunostaining had 52.4%, 38.5%, and 92.3% sensitivity, respectively, and 76.2%, 94.8%, and 99% specificity, respectively. The positive predictive value of cytology, colposcopy, and p16INK4a immunostaining was 31.4%, 66.7%, and 96%, respectively, and the negative predictive value was 88.5%, 85.1%, and 97.9%, respectively. Compared with H&E staining, the kappa of cytology, colposcopy, and p16INK4a immunostaining was 0.327, 0.323, and 0.926, respectively. Conclusion: Positive p16INK4a immunostaining is very strongly consistent with an H&E diagnosis of CIN2+, and it can be used as an objective detection index for HSIL+ diagnosis of HPV-negative patients with CIN2+.

Role of HPV genotyping in risk assessment among cytology diagnosis categories: analysis of 4562 cases with cytology–HPV cotesting and follow-up biopsies

2019 ◽  
Vol 29 (2) ◽  
pp. 234-241 ◽  
Author(s):  
Yimin Ge ◽  
Paul Christensen ◽  
Eric Luna ◽  
Donna Armylagos ◽  
Jiaqiong Xu ◽  
...  
Keyword(s):  
High Risk ◽  
Positive Predictive Value ◽  
Predictive Value ◽  
High Grade ◽  
Squamous Intraepithelial Lesions ◽  
Squamous Cells ◽  
Hpv Genotyping ◽  
High Risk Hpv ◽  
Intraepithelial Lesions ◽  
Undetermined Significance

ObjectiveHuman papilloma virus (HPV) detection and genotyping are increasingly used in clinical risk assessment. We aimed to analyze HPV genotyping performance in risk stratification among cytology diagnosis categories.MethodsBetween January 1, 2015 and December 31, 2016, 4562 cases with cytology–HPV co-testing and biopsy follow-up were identified. HPV tests were performed on Cobas (n=3959) or Aptima (n=603) platforms. Of the biopsies, 669 demonstrated high-grade squamous intraepithelial lesions or worse.ResultsPooled high-risk HPV testing had high overall sensitivity (97%) but low specificity (20%) and positive predictive value (20%) for biopsy-confirmed high-grade squamous intraepithelial lesions or worse. HPV16/18 genotyping had considerably improved specificity (81%) and positive predictve value (35%) in predicting high-grade squamous intraepithelial lesions or worse, especially in atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion categories. Significantly more biopsy-confirmed high-grade squamous intraepithelial lesions or worse were detected by Aptima than Cobas testing, as measured by HPV16/18 (48% vs 33%, p<0.001), non-16/18 high-risk HPV (18% vs 13%, p=0.029), or all high-risk HPV genotypes (27% vs 19%, p<0.001). Aptima genotyping showed a significantly higher positive predictive value than Cobas genotyping for biopsy-confirmed high-grade squamous intraepithelial lesions or worse in the atypical squamous cells of undetermined significance category (47% vs 23%, p<0.05).ConclusionsHPV genotyping was sensitive for biopsy-confirmed high-grade squamous intraepithelial lesions or worse in all cytologic categories, and is particularly valuable in risk evaluation for women with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions. The triaging role was greatly diminished in high-risk lesions (atypical glandular cells, atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions) due to low specificity and positive predictive value. Aptima performance in risk management was superior to Cobas, with significantly higher positive predictive value for biopsy-confirmed high-grade squamous intraepithelial lesions or worse. Our results highlight the importance of careful data interpretation from studies using different HPV testing methods and the need to incorporate HPV E6/E7-mRNA testing into management guidelines.

PECULIARITIES OF PAPILLOMAVIRUS GENOTYPING IN PATIENTS WITH CERVICAL INTRAEPITHELIAL NEOPLASIA

2020 ◽  
pp. 104-111
Author(s):  
N.A. Shmakova ◽  
G.N. Chistyakova ◽  
I.N. Kononova ◽  
I.I. Remizova
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Viral Load ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Squamous Intraepithelial Lesions ◽  
Hpv 16 ◽  
The World ◽  
Intraepithelial Lesions ◽  
Hpv 18

Recently, there has been a steady growth of cervical cancer all over the world, especially in Russia. Patients with cervical cancer have become much younger. At the same time, the human papillomavirus is not only the main factor in the neoplastic process, but it is also one of the most common sexually transmitted infections in the world. The aim of the paper is to assess the prevalence and characteristics of human papillomavirus genotypes in patients with cervical intraepithelial neoplasia. Materials and Methods. During the periodic screening we examined 213 women of a reproductive age with HPV infection. All patients underwent liquid-based cytology and human papillomavirus genotyping by polymerase chain reaction. Results. We revealed that the prevalence of cervical intraepithelial neoplasia among women with papillomavirus infection was 80.3 % (n=171). According to human papillomavirus genotyping, HPV 16 (38 %) and HPV 33 (32 %) prevailed. We also observed positive high correlation between high-grade squamous intraepithelial lesions (HSIL) and HPV 18 (r=+0.759, p=0.001), a negative mean correlation between HPV 45 and low-grade squamous intraepithelial lesions (LSIL) (r=-0.643, p=0.002). A cohort of patients with severe intraepithelial cervical lesions demonstrated high viral load rates. Conclusion. According to the results obtained, we established the dominance of HPV 16 and HPV 33 genotypes in cervical intraepithelial neoplasia. There were significant differences between HSIL and LSIL patients with HPV 18 and HPV 45. There was also a correlation between an increase in the viral load with the severity of the pathological process. Keywords: human papillomavirus, intraepithelial cervical neoplasms, cervical cancer. В последние годы в мире, особенно в России, наблюдается неуклонный рост и «омолаживание» рака шейки матки. При этом вирус папилломы человека является не только основным фактором прогрессирования неопластического процесса, но и одной из наиболее распространенных инфекций, предаваемых половым путем, в мире. Цель. Оценить распространенность и характеристику генотипов папилломавирусной инфекции у пациенток с цервикальными интраэпителиальными неоплазиями. Материалы и методы. Проведено обследование 213 пациенток репродуктивного возраста с ВПЧ-инфекцией, пришедших на профилактический осмотр. Всем женщинам было выполнено цитологическое исследование жидкостным методом и генотипирование вируса папилломы человека методом полимеразной цепной реакции. Результаты. Распространенность цервикальных интраэпителиальных неоплазий среди женщин с папилломавирусной инфекцией составила 80,3 % (171 пациентка). Согласно данным генотипирования вируса папилломы человека превалировал 16-й (38 %) и 33-й типы (32 %). Выявлена положительная высокая корреляционная связь между цервикальными неоплазиями высокой степени онкогенного риска (HSIL) и 18-м типом ВПЧ-инфекции (r=+0,759 при р=0,001), отрицательная средняя корреляционная связь 45-го типа ВПЧ с низкой степенью онкогенного риска (LSIL) (r=-0,643 при р=0,002). Продемонстрированы высокие показатели вирусной нагрузки в когорте пациенток с тяжелыми внутриэпителиальными цервикальными поражениями. Выводы. По результатам полученных данных установлено доминирование 16-го и 33-го генотипов ВПЧ при цервикальных интраэпителиальных неоплазиях с наличием значимых различий между пациентами с HSIL и LSIL в отношении 18-го и 45-го типов, а также связь роста уровня вирусной нагрузки с увеличением степени тяжести патологического процесса. Ключевые слова: вирус папилломы человека, интраэпителиальные новообразования шейки матки, рак шейки матки.

Prognostic markers of high-grade squamous intraepithelial lesions: the role of p16INK4aand high-risk human papillomavirus

2007 ◽  
Vol 86 (1) ◽  
pp. 94-98 ◽  
Author(s):  
José Eleutério Jr ◽  
Paulo César Giraldo ◽  
Ana Katherine Gonçalves ◽  
Diane Isabelle Magno Cavalcante ◽  
Francisco Valdeci de Almeida Ferreira ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Prognostic Markers ◽  
High Grade ◽  
Squamous Intraepithelial Lesions ◽  
Intraepithelial Lesions

scholarly journals Cervical Microbiome and Response to a Human Papillomavirus Therapeutic Vaccine for Treating High-Grade Cervical Squamous Intraepithelial Lesion

2019 ◽  
Vol 18 ◽  
pp. 153473541989306 ◽  
Author(s):  
Rahul Ravilla ◽  
Hannah N. Coleman ◽  
Cheryl-Emiliane Chow ◽  
Luisa Chan ◽  
Barbara J. Fuhrman ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Phase I ◽  
Therapeutic Vaccine ◽  
High Grade ◽  
T Helper ◽  
Squamous Intraepithelial Lesions ◽  
Hpv 16 ◽  
Intraepithelial Lesions ◽  
Helper Type

Human papillomavirus (HPV) infection is associated with the vast majority of cervical cancer cases as well as with other anogenital cancers. PepCan is an investigational HPV therapeutic vaccine for treating cervical high-grade squamous intraepithelial lesions. The present study was performed to test whether the cervical microbiome influences vaccine responses and to explore host factors as determinants of the cervical microbiome composition in women with biopsy-proven high-grade squamous intraepithelial lesions. In a recently completed Phase I clinical trial of PepCan, histological response rate of 45% (14 of 31 patients), a significant increase in circulating T-helper type 1 cells, and a significant decrease in HPV 16 viral load were reported. DNA, extracted from liquid cytology specimens collected before and after vaccinations, were amplified and then hybridized to a G4 PhyloChip assay to characterize the microbiome. We describe trends that certain bacterial taxa in the cervix may be enriched in non-responders in comparison to responders ( Padj = .052 for phylum Caldithrix and Padj = .059 for phylum Nitrospirae). There was no difference in bacterial diversity between the 2 groups. A permutational analysis of variance performed for various demographic and immune parameters showed significant clustering with microbiome beta diversity for race, HPV 16 status, peripheral T-helper type 1 cells, and HLA-B40 ( P = .001, .014, .037, and .024, respectively). Further analyses showed significant differences at the empirical Operational Taxonomic Unit level for race and HPV 16 status. As these results are from a small Phase I study, further studies are needed to examine the role of cervical microbiome in response to HPV therapeutic vaccines.

Comparison of Human Papillomavirus Genotypes in Penile Intraepithelial Neoplasia and Associated Lesions: LCM-PCR Study of 87 Lesions in 8 Patients

2019 ◽  
Vol 28 (3) ◽  
pp. 265-272 ◽  
Author(s):  
María José Fernández-Nestosa ◽  
Nuria Guimerà ◽  
Diego F. Sanchez ◽  
Sofía Cañete-Portillo ◽  
Antonella Lobatti ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Precancerous Lesions ◽  
Intraepithelial Neoplasia ◽  
Associated Lesions ◽  
Hpv Genotypes ◽  
Flat Lesions ◽  
High Risk Hpv ◽  
Intraepithelial Lesions ◽  
Penile Intraepithelial Neoplasia

Penile intraepithelial neoplasia (PeIN) is currently classified in human papillomavirus (HPV)- and non-HPV-related subtypes with variable HPV genotypes. PeINs are frequently associated with other intraepithelial lesions in the same specimen. The aim of this study was to detect and compare HPV genotypes in PeINs and associated lesions using high-precision laser capture microdissection-polymerase chain reaction and p16INK4a immunostaining. We evaluated resected penile specimens from 8 patients and identified 33 PeINs and 54 associated lesions. The most common subtype was warty PeIN, followed by warty-basaloid and basaloid PeIN. Associated lesions were classical condylomas (17 cases), atypical classical condylomas (2 cases), flat condylomas (9 cases), atypical flat condylomas (6 cases), flat lesions with mild atypia (12 cases), and squamous hyperplasia (8 cases). After a comparison, identical HPV genotypes were found in PeIN and associated lesions in the majority of the patients (7 of 8 patients). HPV16 was the most common genotype present in both PeIN and corresponding associated lesion (50% of the patients). Nonspecific flat lesions with mild atypia, classical condylomas, and atypical condylomas were the type of associated lesions most commonly related to HPV16. Other high-risk HPV genotypes present in PeIN and associated nonspecific flat lesion with mild atypia were HPV35 and HPV39. In this study of HPV in the microenvironment of penile precancerous lesions, we identified identical high-risk HPV genotypes in PeIN and classical, flat, or atypical condylomas and, specially, in nonspecific flat lesions with mild atypia. It is possible that some of these lesions represent hitherto unrecognized precancerous lesions.

8. Human papillomavirus mRNA testing for the detection of anal high-grade squamous intraepithelial lesions in HIV-positive men who have sex with men

Sexual Health ◽  
2013 ◽  
Vol 10 (6) ◽  
pp. 573
Author(s):  
Elena Sendagorta Cudós ◽  
Maria P. Romero Gomez ◽  
Beatriz Hernandez Novoa ◽  
Ander Mayor ◽  
Jose I. Bernardino De La Serna ◽  
...  
Keyword(s):  
Predictive Value ◽  
Screening Program ◽  
University Hospital ◽  
High Grade ◽  
Squamous Intraepithelial Lesions ◽  
Cross Sectional ◽  
Hpv Dna ◽  
Hpv E6 ◽  
Anal Cytology ◽  
Intraepithelial Lesions

Background Currently, screening for anal high-grade squamous intraepithelial lesions (HSIL) relies on anal cytology and high-resolution anoscopy (HRA). Since this approach has limited sensitivity and specificity for detecting anal HSIL, there is increasing interest in the role of biomarkers for predicting anal HSIL. The aim of this study is to evaluate the diagnostic accuracy of HPV E6/E7-mRNA expression for the detection of anal HSIL in MSM HIV-infected patients, in comparison to DNA-HR-HPV and anal cytology. Methods: This cross-sectional screening study included 101 MSM followed at the HIV-unit of La Paz University Hospital. Intra-anal swabs from patients participating in a screening program including cytology, HRA and histology were analysed. HR-HPV-DNA detection was performed by means of the CLART HPV2 assay (GENOMICA SAU.). E6/E7-mRNA detection of HR-HPV types 16, 18, 31, 33 and 45 was performed using the NucliSENS-EasyQ assay (BioMérieux, Marcy l’Etoile, France). Results: HR-HPV DNA and HPV E6/E7 mRNA were detected in 82% and 57% of the anal smears, respectively. Anal cytology screening was abnormal in 70.3%. For the detection of HSIL sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.7%, 55.6%, 57.9%, and 69.8% for E6/E7-mRNA testing, respectively, compared with 97.9%, 31.5%, 55.4% and 94.4%, respectively, for HR-HPV DNA testing and 83%, 40.7%, 54.9%, 73.3%, respectively, for cytology testing. Conclusions: In comparison with the other tests, the NucliSENS EasyQ HPV assay yielded a lower clinical sensitivity but a higher clinical specificity and PPV for the detection of anal HSIL in MSM HIV-infected patients.

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