Human Papillomavirus Detection and Abnormal Anal Cytology in HIV-infected Patients Using p16/Ki-67 Dual-Staining

Patarapadungkit, Natcha; Khonhan, Parinyabhorn; Pisuttimarn, Pornrith; Pientong, Chamsai; Ekalaksananan, Tipaya; Koonmee, Supinda

doi:10.31557/apjcp.2020.21.7.2013

Cited by 5 publications

(7 citation statements)

References 29 publications

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“…For all the biomarkers, we observed that, in HIV-infected MSM, the positivity rate increased significantly with the grade of the cytological alterations, consistently with previous studies [ 21 , 25 , 26 ] and a recent meta-analysis [ 4 ]. Differently, we did not observe this trend in HIV-uninfected MSM, probably due to the limited number of samples evaluated for this subgroup.…”

Section: Discussionsupporting

confidence: 90%

“…Moreover, the cytological categories showed different predictive values in the identification of histological HSILs [ 16 ]. In order to improve the detection of these lesions and to use more objective methods, several HPV-related biomarkers have been evaluated, mainly in HIV-infected MSM [ 17 , 18 , 19 , 20 , 21 , 22 ]. High-risk (hr)HPV E6/E7 mRNA (thereafter hrHPV mRNA) has gained attention because it indicates an active and transforming HPV infection.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of HPV-Related Biomarkers in Anal Cytological Samples from HIV-Uninfected and HIV-Infected MSM

et al. 2021

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Men who have sex with men (MSM) harbor the highest risk for anal carcinoma, mainly caused by Human Papillomavirus (HPV). The use of HPV-related biomarkers in the screening for this neoplasia is still debated. We assessed the association between high-risk (hr)HPV DNA, HPV16/18 DNA, hrHPV E6/E7 mRNA, and p16/Ki-67 with cytological abnormalities (any grade) and high-grade intraepithelial lesions (HSIL) in HIV-uninfected and HIV-infected MSM. Overall, 150 cytological samples in PreservCyt (Hologic), with a negative to HSIL report, were analyzed for hrHPV DNA, hrHPV E6/E7 mRNA, and p16/Ki-67 using the Linear Array (Roche), Aptima (Hologic), and CINtec® PLUS (Roche) assays. In HIV-infected MSM, positivity for all the biomarkers significantly increased with the cytological grade. In both populations, the association of hrHPV E6/E7 mRNA and p16/Ki-67 positivity with HPV16 did not differ significantly compared to hrHPVs other than HPV16. In HIV-uninfected MSM, the odds of having an HSIL increased approximately six times for the p16/Ki-67 positive cases. In HIV-infected individuals, all the biomarkers showed a significant association with HSIL, except for hrHPV DNA, with the strongest association observed for p16/Ki-67. The odds of HSIL increased almost 21 times in those positive for this biomarker. Our results encourage further investigation on the use of p16/Ki-67 dual staining in anal cancer screening for HIV-uninfected and HIV-infected MSM.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Evaluation of HPV-Related Biomarkers in Anal Cytological Samples from HIV-Uninfected and HIV-Infected MSM

et al. 2021

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“…Some have focused on anal biopsies 14,15 while others on anal cytology. [16][17][18][19][20][21] High correlation between dual staining on anal cytology specimens and HR-HPV detection has been shown, 17 with high sensitivity for dual staining for AIN3 though low specificity on subsequent biopsy. 18 However, another group found low sensitivity and specificity for dual staining for the detection of biopsy proven HSIL, concluding that p16/Ki67 immunostaining did not improve the diagnostic accuracy of anal cytology.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of dual p16/Ki‐67 immunostaining on anal cytology specimens

Smithgall,

Towne,

Gonzalez

et al. 2024

Diagnostic Cytopathology

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IntroductionDual immunostaining for p16/Ki67 is FDA‐approved for use on liquid‐based cervical cytology specimens; however, the utility of dual staining in anal cytology especially for ASCUS risk stratification is not well established.MethodsWe investigated dual staining performance on anal cytology specimens and correlated with subsequent cytologic interpretation, high‐risk HPV status, and anal biopsy results. Dual staining for p16/Ki‐67 was performed on all liquid‐based anal cytology specimens from December 2021 to June 2022 (n = 43).ResultsThree patients had high grade squamous intraepithelial lesion (HSIL/AIN2‐3) on biopsy; dual staining was positive in all three cases. All HR‐HPV negative cases were negative for dual staining. Among the 12 ASCUS samples with subsequent anal biopsy results all also had HR‐HPV testing. Due to small sample size of cases with squamous intraepithelial lesion (SIL) diagnosed on biopsy, the sensitivity and positive predictive value was not calculated. However, the specificity and negative predictive value of p16/Ki‐67 dual staining for SIL of any grade on biopsy were 1 (95% CI: 0.66–1) and 0.9 (95% CI: 0.65–0.97) respectively, whereas the specificity and negative predictive value of HR‐HPV testing for SIL of any grade on biopsy were 0.44 (95% CI: 0.14–0.79) and 0.8 (95% CI: 0.41–0.96) respectively.ConclusionDual p16/Ki‐67 staining indicates transforming HPV infection and could help serve as an ancillary test for risk stratification for atypical anal cytology specimens. Among ASCUS samples, dual staining was specific for SIL of any grade with a high negative predictive value and therefore could be useful in clinical practices with limited availability for follow‐up care.

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“…The P16 protein is the first tumor suppressor gene found at human chromosome 9p21, which is directly involved in the regulation of cell cycle [40]. P16 is an important molecular marker for HPV infection into cervical cells, and could accumulate in cells, which could be clearly detected by IHC [41][42][43]. Previous studies have shown that the tumor suppressor gene P16 was overexpressed in 99% of hr-HPV positive cervical cancer and precancerous lesions, therefore, P16 protein can be used as a biomarker for early screening of cervical cancer and precancerous lesions [44].…”

Section: Discussionmentioning

confidence: 99%

Expression and Analysis of Rsf-1 and P16 in Cervical Intraepithelial Neoplasia

Zhu¹,

Zhang²,

Tang³

et al. 2022

EJGO

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Objective:The molecular mechanism in the occurrence and progression of cervical intraepithelial neoplasia (CIN) is of great theoretical significance to improve the early diagnosis, treatment and prognostic judgement of CIN in clinical practice. The current study aimed to detect the expression of remodel and space factor-1 (Rsf-1) and P16 in CIN, and to analyze the expression of Rsf-1 and P16 in different stages of CIN and to investigate the possible correlation. Methods: A total of 110 samples of CIN were collected from the Department of Pathology, the First Affiliated Hospital of Bengbu Medical College in 2018. Rsf-1 and P16 was detected by immunohistochemical staining in pathological tissue sections. The correlation between Rsf-1 expression and P16 expression in CIN was further analyzed. Results:The immunohistochemical results of 110 cases of CIN showed that the positive rate of P16 and Rsf-1 gradually increases with the grade of CIN increases. The expression of P16 was significantly different between different CIN grade (p = 0.011). The expression of Rsf-1 was also significantly different in different CIN grade (p = 0.015). Conclusions: Rsf-1 and P16 was highly expressed or over-expressed in high-grade CIN, and the positive rate of their expression increased with the increase in CIN grade.

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Human Papillomavirus Detection and Abnormal Anal Cytology in HIV-infected Patients Using p16/Ki-67 Dual-Staining

Cited by 5 publications

References 29 publications

Evaluation of HPV-Related Biomarkers in Anal Cytological Samples from HIV-Uninfected and HIV-Infected MSM

Evaluation of HPV-Related Biomarkers in Anal Cytological Samples from HIV-Uninfected and HIV-Infected MSM

Evaluation of dual p16/Ki‐67 immunostaining on anal cytology specimens

Expression and Analysis of Rsf-1 and P16 in Cervical Intraepithelial Neoplasia

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