Role of Dual-Staining p16/Ki-67 in the Management of Patients under 30 Years with ASC-US/L-SIL
, Andrea Pasquini 2,3,*, Delia Zahoi 4, Andrei Motoc 4, Diana Lungeanu 2, Oana Balint 1, Aurora Ilian 1, Ligia Balulescu 1, Dorin Grigoras 1 and Laurentiu Pirtea 1
Round 1
Reviewer 1 Report
MS title:
Role of dual-staining p16/Ki-67 in the management of patients under 30 years with ASC-US/L-SIL
This MS is interesting since it highlights a remarkable potential of dual-staining p16/Ki-67 in the management of patients under 30 years with ASC-US/L-SIL.
Some modifications of the MS are suggested below [marked in red].
1.In the title - PLEASE, EXPLAIN THIS ABBREVIATION: ASC-US/L-SIL
2.In the Abstract
Patients diagnosed with L-SIL [PLEASE, EXPLAIN THIS ABBREVIATION] or ASC-US [PLEASE, EXPLAIN THIS ABBREVIATION] are subjected to additional investigations, such as colposcopy and biopsy, to rule out CIN2+ [PLEASE, EXPLAIN THIS ABBREVIATION]. Especially in young patients, lesions tend to regress spontaneously and many HPV infections are transient. Dual-staining p16/Ki-67 has been proposed for the triage of patients with ASC-US or L-SIL, but no prospective study addressing only this subgroup of patients has been conducted so far. We performed a prospective study including all eligible patients referred for LEEP [PLEASE, EXPLAIN THIS ABBREVIATION] in our department PLEASE, PUT THE NAME & LOCATION]. HPV genotyping and dual staining for p16/Ki-67 were performed prior to LEEP at 6 and 12 months after LEEP. A total of 60 patients were included in the study and completed the follow-up evaluation. We analyzed the sensitivity and specificity for biopsy-confirmed CIN2+ using the 95% CI of HR-HPV [PLEASE, EXPLAIN THIS ABBREVIATION], p16/Ki-67 dual-staining, colposcopy, and combinations of tests on all patients and separately for the ASC-US and L-SIL groups. Dual-staining p16/Ki-67 alone or in combination with HR-HPV and/or colposcopy showed a higher specificity than HR-HPV and/or colposcopy for the diagnosis of biopsy-confirmed CIN2+ in patients under 30 years. Colposcopy+ p16/Ki-67 and HR-HPV + colposcopy + p16/Ki-67 showed the highest specificity in our study.
3.In Figure 1 – Study flow chart. The patients in the ASC-US and L-SIL groups were followed-up for 12 months after LEEP [PLEASE, EXPLAIN ALL THE ABBREVIATIONS - in the legend].
- 3.4. Dual staing [PLEASE, make these CORRECTIONS in many places] = Dual-staining
- In the discussion - PLEASE, PUT A SECTION RE: STRENGTHS & LIMITATIONS OF THE STUDY]
- In the Conclusions
Dual-staining p16/Ki-67 alone or in combination with HR-HPV and/or colposcopy showed a higher specificity than HR-HPV and/or colposcopy for the diagnosis of biopsy-confirmed CIN2+ in patients under 30 years. Colposcopy+p16/Ki-67 and HR-HPV+ colposcopy+p16/Ki-67 showed the highest specificity in our study. Therefore, we consider that the p16/Ki-67 test could be useful in the triage of young patients with ASC-US or L-SIL and should be taken into consideration for the diagnostic algorithm of this subgroup of patients. [PLEASE, make these CORRECTIONS in the Conclusions]
- PLEASE, PUT AN ABBREVIATION LIST at the end of this MS.
Author Response
"Please see the attachment."
Author Response File: 
Author Response.docx
Reviewer 2 Report
Very interesting article
Reviewer 3 Report
This is a prospective study which analyzed the role of dual-staining p16/Ki-67 in the management of patients under 30 years with ASC-US/L-SIL. Currently, there is no sufficient evidence available in literature for the triage of ASC-US and L-SIL patients <30 years by using dual-staining. Thus, the current study demonstrates a good novelty and promising significance for management of women <30 years with abnormal cytology of ASC-US/L-SIL. There are some minor limitations listed below:
1.A total of 60 patients were included in the current study, which is a small number of cohort, thus, it might be more convincing that more patients could be enrolled.
2. A very comprehensive discussion in the Discussion section, however, I would rather not discuss “Non-HPV cervical cancer” and “Dual-staining in pregnancy” which are not correlated to the main subject of this study.
Author Response
"Please see the attachment."
Author Response File: Author Response.docx
