Title: Age-period-cohort analysis of global, regional, and national cervical cancer prevalence
trends in women of childbearing age (15–49 years), 1990–2021
Version: 0 Date: 27 May 2025
Reviewer's report:
The manuscript under consideration addresses a subject of pivotal importance to public health:
cervical cancer. While the study was intriguing, the authors' decision to focus on women of
reproductive age (15 to 49 years) for a cervical cancer prevalence study was not adequately
justified. In consideration of the natural history of the disease, young women, despite being more
susceptible to infection by the HPV virus, tend to spontaneously resolve the infection and do not
progress to the disease, or even to the development of precursor lesions. The incidence of the
disease peaks around the age of 50, and the choice excluded a large proportion of cancer cases
in the female population, hindering analysis of the age and cohort analysis.
Cases occurring before the age of 25 are rare, and there are papers in the literature that suggest
the histological profile of these cancers may be different and more aggressive, and less subject to
prevention through screening strategies. This particular issue was not addressed by the authors.
The discourse surrounding individuals between the ages of 15 and 24 does not appear to be
particularly pertinent to the prevalent cases of cancer. Instead, it seems more suitable for the
discussion of HPV infection, which has the potential to be mitigated through vaccination.
In regard to the remaining aspects, it is my opinion that the discussion of the age analysis without
addressing the more advanced age groups is incomplete. It should be noted that the target age
range for screening in most countries with screening programs was not mentioned, as well as the
World Health Organization's current recommendation for eliminating cervical cancer, which is
to screen women at least twice in their lives, at 35 and 45 years of age. This could justify the
sharper drop in these age groups.
Additionally, it would have been beneficial for the discussion to address the impact of
vaccination on the observed cohort and period analysis. It is important to note that the
introduction of vaccination programs in high-income countries began in 2008. Consequently,
the girls who were vaccinated at that time would, by the conclusion of the analysis period (2019,
11 years later), have reached the age at which screening initiates.
A notable aspect that has not been addressed is the elevated prevalence of HIV in certain
countries, and the increased risk of HPV infection persisting and developing cervical cancer in
immunosuppressed women.
Furthermore, it would be important to cite studies that demonstrate a substantial decline in
incidence in countries that have adopted organized screening programs, particularly in high-
income nations, when conducting a period analysis.
A considerable body of research has been conducted on this subject, predominantly in European
countries that have adopted unified health systems.
It must be acknowledged that, despite the GBD's status as a valuable instrument in health
research, its limitations must be recognized and highlighted, particularly in the context of data
availability and quality, particularly in low-income countries.