All reviews of published articles are made public. This includes manuscript files, peer review comments, author rebuttals and revised materials. Note: This was optional for articles submitted before 13 February 2023.
Peer reviewers are encouraged (but not required) to provide their names to the authors when submitting their peer review. If they agree to provide their name, then their personal profile page will reflect a public acknowledgment that they performed a review (even if the article is rejected). If the article is accepted, then reviewers who provided their name will be associated with the article itself.
The authors have addressed all the points raised satisfactorily and the manuscript should now be published
Risk stratification of women with cervical cancer is an important area of research – According to WHO statistics, cervical cancer caused by HPV infection is the 4th biggest cause of death from cancer in women worldwide. Treatment success depends upon tumour type and host response to the tumour.
This paper looks at the feasibility of using immunostaining of tumour infiltrating immune cells in conventional biopsies to aid risk stratification of cervical cancer in a study of Chinese women. The authors use standard techniques that would be widely available within hospital pathology laboratories which makes exploitation of the results feasible in clinical settings. There are several reports in a variety of tumours that different types of immune cells can be identified and have some prognostic value but this differs between tumour type. Here the authors have found that in cervical cancer the presence of activated or memory T cells (CD45RO+ve cells) and regulatory T cells (FOXP3+ve cells) could be useful in determining outcomes for patients and used as a guide in clinical management of cases.
The reviewers are happy with the manuscript apart from some minor corrections. The paper is well and concisely written and the tests have been appropriately applied and analysed. The statistical analysis is appropriate for the data presented. Antibodies used are commercially available and are correctly annotated. The representative immunostaining micrographs presented are generally clear and easy to interpret. As reviewer 1 notes the number of tumours that were HPV+ve is lower than would be expected and the authors may have been reliant on data generated using a less sensitive HPV detection assay than conventional in the UK or USA – the authors need to provide information on this assay and discuss its relative sensitivity to other commercially available assays.
Please address the comments raised by the reviewers.
This manuscript is very well-written. The main points are clearly stated. Sufficient background is provided with citation of appropriate literature. The manuscript is well structured and the figure and tables are presented professionally. The article is concise and self-contained with a hypothesis and relevant discussion.
The manuscript describes primary research on a small cohort of formalin-fixed paraffin-embedded cervical cancer samples. The work relies on pathologists’ assessment of staining of tissues sections with various markers of infiltrating immune cells, and on interpretation related to a good range of clinical data. The research question is well defined and meets a gap in knowledge. However, data are related to “risk stratification” in cervical cancer patients but I could not find any definition of what the authors consider low, intermediate, or high risk. Is this metastasis, recurrence, death before 5 years, or something else? This should be stated in the manuscript.
Generally, methods are well described but there is no description, or reference to, the methods/tests used to originally determine variables such as HPV status (see below) or physiological data such as renal and liver function.
The article is valid. The only negative for the study is that the cohort is small, but the authors acknowledge this, and the p-values are significant.
The HPV typing data is striking. It is unusual to find 16% of cervical cancer patients are HPV-negative (expected value ~<5%). This is why it is important for the authors to state the method used to determine HPV status.
The authors state that they see membrane staining for the majority of their immune markers in the IHC analysis (Figure 1). However, although they might expect to find membrane CD8, it looks to be cytoplasmic in the picture shown (Figure 1 E). It is very hard to be certain of the cellular position of staining with these markers at the magnification shown. It might be best to simply state that positive staining was observed.
The paper is well written and in plain clear English. It is easy to read and understand.
References sufficient. Data is well organised.
No typographical errors were detected and
Experimental design is well suited for the research question. methods described in sufficient detail. Two further clarifications in methods will improve the manuscript .
1. Lines 124-126 – Patients are classified based on their risk based on prognosis. It will be useful here to have a bit more detail on how the patients were classified.
2. HPV test was used- details of what test was used can be added.
findings are clearly shown and look valid based on the data provided.
This is a simple and clear paper that shows the assessment of TILs cervical cancer tissue. I would like to recommend that the paper is accepted for publication.
All text and materials provided via this peer-review history page are made available under a Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.