Reviewer’s report
Title: 
Cervical cancer in women under 30 years of age in Norway; a population-
based cohort study
Version: 
1 
Date: 
21 Sep 2020
Reviewer's report:
Thanks for the opportunity to review the revised paper.
Although the paper has improved significantly, I still find that several critical
issues remain unresolved.
Overall
1. Although I strongly recommended the paper be reviewed by a native speaker
to improve the wording, this has not been done. There are still several
grammatical errors throughout the paper. Please revise! Also, the paper would
benefit from being re-organized. For example, it doesn't make sense to start
describing incidence rates (in the Results) and then describe basic characteristics.
Understanding the study cohort helps to better understand/interpret incidence
rates. The results are hard to read, and the discussion should be rewritten
completely. The authors mostly compare the current trends in incidence and risk
of death with other studies (which they should), but it should be condensed.
More attention should be directed toward a discussion of potential reasons for
the current findings. Including information on temporal changes in covariates
would enable this.
Methods and Results
2. Respectfully, I am not satisfied with the response from the authors with
respect to correction for hysterectomy. This is a major limitation, particularly
because the authors compare incidence rates with women aged 30 years and
older (who are more likely to have had a hysterectomy, resulting in
underestimated rates). Although hysterectomy incidence rates are low compared
to countries like the US, Germany and the UK, rates are very similar compared
to Denmark. Given that risk of hysterectomy increases with age, rates among
women aged 30+ are likely underestimated, particularly in the beginning of the
study period (where rates were likely higher than today). Thus, not correcting for
hysterectomy affects the results. I acknowledge that information on hysterectomy
status cannot be collected from the cancer registry, but Norway has other
registries from where this information is available. Using the personal
identification number would enable the authors to correct for hysterectomy at the
individual level. Several studies have clearly demonstrated the importance of
this. If the authors don't want to retrieve information on hysterectomy status, the
authors should acknowledge this major limitation in greater detail!
3. Given that screening status is used, more information is needed about the
Norwegian cervical cancer screening program. It is only mentioned briefly in the
discussion. In many countries, the screening interval is extended in older women
(say 50+). If Norwegian women aged 50+ are screened every 5 years that would
explain the very high proportion of women who had not had a cervical cytology
test in the preceding 3.5 years. If screening interval varies by age, it would be
appropriate to take this into account, for example by reporting the proportion of
women not screened in the preceding 5.5. years.
4. https://www.kreftregisteret.no/globalassets/cancer-in-
norway/2018/cin2018.pdf. Here it is stated that all precancerous lesions should
be recorded. The authors state that "certain" precancerous lesions should be
recorded.
5. How were the histological subtypes grouped? How about those cases that may
have been an uterine corpus cancer. What was the difference between
unspecified morphology and other malignancy? I suggest the authors include a
table, summarizing the grouping of histological subtypes in the supplementary.
Furthermore, the authors should exclude cases with uncertainty about the
originating site. 
6. With regards to Nelson-Aalen cumulative hazard function, the authors should
mention death due to cervical cancer AND death due to other causes as
censoring events.
7. More information is needed on how incidence rates were calculated. How was
person-time at risk defined? Emigration/immigration - is this information
available from the cancer registry or somewhere else. This should be clarified.
8. Joint point regression analysis. More information is needed on the methods.
The authors should explain WHAT is being measured and how. The results seem
wrong. Typically, annual percentage change (APC) is estimated and not %. So, I
don't understand from where the % is derived?
9. I like that the authors added Table 2, however, it is hard to read. Given that
the authors want to stress out differences in stage between women aged <30 vs.
those aged 30+, I suggest to categorize in age groups at the far left and then
stratify by FIGO. That would probably make the Table more readable.
10. Given that the authors focus on temporal trends in incidence rates and risk of
dying from cervical cancer, it would be of great importance to make a table,
summarizing changes in variables over time, as this would help explain WHY
the temporal changes are observed. I am aware that the authors mention this in
the text, but the numbers should be included in a Table
Discussion:
11. Se above
12. Of note, HPV vaccination will likely affect cervical cancer incidence overall
due to herd immunity, especially given the high vaccination coverage in
Norway. 
Conclusion:
13. Concluding that the increase in cervical cancer incidence among younger
women may be due to changes in sexual behavior may be true, but it seems off
to include it in the conclusion without discussing at all.
14. This sentence does not seem to be justified by the results: "The screening
program implemented in 1995 has had a high impact on cervical cancer
incidence in the Norwegian population." I am confident this is true, but as it is
stated in the conclusion it appears as if this was one of the study's main findings,
which it isn't.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
none
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please publish my name with my
report.
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?
Yes
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes