Reviewer’s report
Title: 
Women's Cancers in China: A Spatio-Temporal Epidemiology Analysis
Version: 
0 
Date: 
05 Jan 2021
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses a
testable research question(s) (brief or other article types: is there a clear
objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work
technically sound? If not, can revisions be made to make the work technically
sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: 
The analysis is quite clear, and the paper appears well-written and detailed, but
some technical issues need to be clarified, and there is a need to be more focused
on some aspects. In particular, the statistical methods appear weak and outmoded
by some recent methods based on spatio-temporal BYM maps.
REQUESTED REVISIONS: 
The manuscript proposed the use of statistical methods to conduct a spatio-
temporal epidemiology analysis on breast, cervical, and ovarian cancers in
China, analyzing data of the national registry between 2010 and 2015. 
The analysis considered both the incidence and the mortality in China, which is
a country with a rapid growth in the number of the elderly and then of cancers, in
particular of those which are related to the age. Besides, since 2000, China has
started several screening programs with mixed results in terms of participation
rate and identification work-flow.
The statistical analysis considered two indices (Moran's I statistics and
Kulldorff's spacetime scan statistics) that are commonly used in analyzing the
spatio-temporal data set. 
The analysis is quite clear, and the paper appears well-written and detailed, but
some technical issues need to be clarified, and there is a need to be more focused
on some aspects. In particular, the statistical methods appear weak and outmoded
by some recent methods based on spatio-temporal BYM maps. Some major
issues are reported below:
1) The Moran's I statistics and Kulldorff's space-time scan statistics find a proper
use when the data set does not have a reference value, while it is well-known that
mortality and incidence have national reference rates. 
The natural use of Moran's I is to find a spatial discontinuity across a continuous
spatial pattern (or evenly with a high spatial dimension) for discovering "hot
spots" in infecting diseases. The use of Moran's I for this application may have
several limitations; the first is due to the presence of provinces of different sizes
such that the adjacency matrix cannot be taken into account. Kulldorff's space-
time scan statistics considers only cylindric windows in space; it has some
difficulties in detecting non-circular clusters.
2) The introduction is lacking of a more exhaustive comparison with the
mortality rates with other emergent countries and with Western countries that
have reached more stable rates. Also, I suggest rewriting the introduction
considering the actual knowledge shared by international agencies (i.e., IARC
monography, WHO reports, etc. ) 
3) The discussion needs to be reorganized focusing on the attempt to explain the
observed spatial and temporal clusters analyzing in detail, which could be due to
the following sub-aspects:
- time: the introduction of previous screening programs. What is the overall
changes 2010-2015 in cancer among women? (may help to understand the
difference of the considered cancers from the overall trend)
- space: spatial differences in terms of habit and/or risk factor among provinces
(province with high hab. density, smoking habit, presence of industrial areas,
etc.), or in the adoption of screening program. The findings showed some
relevant, for example, for the Shanghai province.
Other minor issues:
Page 4: "It is caused by the sexually transmitted human papillomavirus (HPV)
under most circumstances" Yes, but not only. Please report and explain under
adequate citations.
Page 5: "In the academic world, more and more attention has been paid to the
epidemics of women's cancers in China"--do you have a motivation? Could you
explain?
Page 8: reference 27 is related to a paper in which Moran's I index did not report
the presence of a spatial cluster, but I suggest using as a reference a citation
about the mathematical features of the Moran's I index.
Page 9: In "high-high (HH, geographical units with high value surrounded by
geographical units with low value", but high-high areas have a positive
correlation with their neighbors, so the definition is wrong. The same for the
high-low. Please check.
Page 9: As reported in "the geographic size of the window was limited to half
the expected number of cases", is there a reason to restrict the space not in sq.
km but a portion of the population?
Page 10: "The seasonal scan statistic"--did you mean "space-time scan
statistics?" or something similar?
Page 11: The reported rates on Table 1 are those from the national registry? The
statistical significance reported--which test is it based on? Also, the title in Table
1 needs to be fixed.
Discussion page 1: "across to" -> "across"
Discussion page 2: "dense breast" -> dense breasts or breast density
Discussion page 2: "was experimented but was terminated"--check the verbs'
consistency.
Discussion page 3: "it has not listed" -> it has not been listed
Discussion page 2-3: "Besides, numerous studies have applied models to explore
the risk factors of women's cancers based on the Chinese sample, which serves
as evidence for predicting the individual breast cancer risk of Chinese women."
This sentence is lacking a citation for supporting its meaning.
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Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes