Peer Review History

Original SubmissionSeptember 19, 2019
Decision Letter - Muy-Teck Teh, Editor

PONE-D-19-26374

Recurrence rates after surgical removal of oral leukoplakia - a prospective longitudinal multi-centre study

PLOS ONE

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Muy-Teck Teh, Ph.D.

Academic Editor

PLOS ONE

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: I Don't Know

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: The authors have carried out a very interesting study to determine the causes for recurrence of oral Leukoplakias

The study has been carried out in a very systematic manner,

Oral leukoplakia with dysplasia are potentially premalignant lesions. In the current study the number of cases with dysplasias that is selected are only 22. More number of cases with dysplasias can be evaluated and the recurrence rate and causes for recurrences for these cases should be determined. This will help in identifying high-risk lesions and they can be treated appropriately.

The Kaplan - Meier survival curves are also very interesting. It is interesting to note that the habit of snuff is a causative factor for recurrence.

Reviewer #2: This is an interesting and well performed study on recurrence of oral leukoplakias (OL) following surgical excision. I have only three comments:

1. A definition of oral leukoplakia is given in the introduction, however, I think the definition used by the participating centers should be given also in the patients and methods section.

2. On page 4/5 it is stated that “the inclusion criterion was a clinically and histopathologically verified diagnosis of OL”. Traditionally, histopathology cannot verify an OL, however, the biopsy can rule out other diagnoses and give information on possible epithelial dysplasia/carcinoma. I am sure the authors are aware of this, however, in order not to mislead others, I think the sentence should be changed.

3. In Table 1 lichenoid reaction is given as the histopathological diagnosis in 20 cases. Three questions emerge from this:

a. is this compatible with a final diagnosis of leukoplakia? A short discussion could be included.

b. lichenoid reactions are sometimes seen in relation to contact with dental restorations or other causes. Were there any clinical indications that the cases with histopathologically diagnosed lichenoid reactions had an obvious (or possible) cause such as contact with dental restorations? I think a short mentioning of this should appear in the patients and methods section.

c. how many recurrences were seen in these cases?

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Reviewer #1: Yes: Dr Monica Charlotte Solomon

Reviewer #2: No

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Revision 1

Response to the reviewers´ comments,

Thank you very much for valuable comments. We are much obliged for your thorough revision. Please find our response in italics below.

Please find a point-by-point response to the Reviewers comments below.

Reviewer # 1.

“Oral leukoplakia with dysplasia are potentially premalignant lesions. In the current study the number of cases with dysplasias that is selected are only 22. More number of cases with dysplasias can be evaluated and the recurrence rate and causes for recurrences for these cases should be determined. This will help in identifying high-risk lesions and they can be treated appropriately.”

We agree. But the 22 cases with dysplasia are the patients to date available in this prospective study. However, the ORA-LEU-CAN study is ongoing and we hope in the future to be able to answer the issues raised by the referee.

Reviewer #2.

1) “A definition of oral leukoplakia is given in the introduction, however, I think the definition used by the participating centers should be given also in the patients and methods section#.

The definition of OL has been included in the Patients and Methods section (P.5 para.1).

2) “…the inclusion criterion was a clinically and histopathologically verified diagnosis of OL” is correct.

We agree that OL is a solely clinical diagnosis. The sentence has been rephrased:

“the inclusion criterion was a clinically verified diagnosis of OL” (p.5, para. 1).

3) In Table 1 lichenoid reaction is given as the histopathological diagnosis in 20 cases.

Table 1 illustrates the patients’ characteristics in the entire patient group (N = 180) but we analysed only the 103 patients who had an OL that we were able to be completely remove. Of these seven patients four recurred.

Three questions emerge from this:

a. Is this compatible with a final diagnosis of leukoplakia? A short discussion could be included.

We have elucidated this matter in the Discussion (p.12, para.2):

“In seven patients with OL the histopathological diagnosis was lichenoid reaction. In these patients, records and clinical photos were thoroughly re-reviewed. No clinical signs according to van der Meij et al (26), were found indicating oral lichen planus, oral lichenoid lesion or lichenoid contact reaction. A diagnosis of OL according to WHO (1) postulates exclusion of known diseases or disorders that carry no increased risk of cancer. In the present study we as strictly adhered to this definition. In the WHO definition of OL, histopathological diagnosis is confined to presence of dysplasia or not (1). Thus, excluding known diseases causing a white plaque in the oral mucosa, the histopathological diagnosis lichenoid reaction is compatible with an OL diagnosis.”

b. Lichenoid reactions are sometimes seen in relation to contact with dental restorations or other causes. Were there any clinical indications that the cases with histopathologically diagnosed lichenoid reactions had an obvious (or possible) cause such as contact with dental restorations? I think a short mentioning of this should appear in the patients and methods section.

None of the seven patients had dental fillings in contact with the lesions. A sentence describing this has been added in the manuscript (P.x, para y) In that group seven patients had the histopathological diagnosis lichenoid reaction.

c. How many recurrences were seen in these cases

4 OL out of 7 with the histopathological diagnosis lichenoid reaction recurred.

On behalf of the authors,

Yours sincerely,

Bengt Hasséus, LDS, PhD, Associate Professor

Corresponding author

Dept. of Oral Medicine and Pathology,

Institute of Odontology, Sahlgrenska Academy,

University of Gothenburg,

PO Box 450,

SE 405 30 Gothenburg, Sweden

Email: bengt.hasseus@gu.se

Attachments
Attachment
Submitted filename: Respons to the Reviewers.docx
Decision Letter - Muy-Teck Teh, Editor

Recurrence rates after surgical removal of oral leukoplakia - a prospective longitudinal multi-centre study

PONE-D-19-26374R1

Dear Dr. Hasséus,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Muy-Teck Teh, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Formally Accepted
Acceptance Letter - Muy-Teck Teh, Editor

PONE-D-19-26374R1

Recurrence rates after surgical removal of oral leukoplakia - a prospective longitudinal multi-centre study

Dear Dr. Hasséus:

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If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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on behalf of

Dr. Muy-Teck Teh

Academic Editor

PLOS ONE

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