Human papillomavirus (HPV) vaccination has been recommended for routine use in US women since June 2006.1 Studies from 2022 and 2023 indicated a 12% per year decline (overall, 65% reduction) in cervical cancer incidence during 2012 to 2019 among US women younger than 25 years who likely benefited from HPV vaccination.2,3 Because a reduction in mortality follows a reduction in incidence, we evaluated recent trends in cervical cancer mortality among young women.

Methods

We analyzed cervical cancer mortality data for women aged younger than 25 years from 1992 to 2021 from the National Center for Health Statistics.4 Mortality rates were calculated as deaths per 100 000 persons and age-adjusted to the 2000 US standard population using SEER*Stat version 8.4.3. We assessed trends in mortality rates over time using the National Cancer Institute’s Joinpoint Regression Program version 5.0.2. We calculated the trends by estimating annual percentage changes by fitting a regression line on a logarithmic scale over specified intervals, where each data point represented 3 years of mortality data. The significance of these trends was evaluated using a t test for zero joinpoints (changes in cancer mortality trends) and a z test for 1 or more joinpoints. If a joinpoint occurred, we estimated the number of cervical cancer deaths in the absence of a joinpoint, assuming the prior trend would have continued using the log-transformed linear regression model. Statistical significance was tested at a 2-sided P < .05. The Medical University of South Carolina institutional review board deemed the study exempt from review and waived the requirements for informed consent because publicly available data were used.

Results

Between 1992 and 2021, among women aged younger than 25 years, 398 cervical cancer deaths were reported. From 1992-1994 to 2013-2015, there was an initial gradual decline of 3.7% per year (95% CI, −4.8% to −2.1%) in cervical cancer mortality. Cervical cancer mortality decreased 15.2% per year (95% CI, −21.9% to −7.8%; overall, 62% reduction) from 2013-2015 to 2019-2021 (Figure, A). The number of cervical cancer deaths decreased during this same time period, from 55 in 1992-1994 to 35 in 2013-2015 to 13 in 2019-2021 (Figure, B). Assuming that the trend from 1992-1994 to 2013-2015 would have continued, an estimated 26 additional cervical cancer deaths would have been expected to occur between 2016 to 2021, based on projected mortality rates.

Figure.  Trends in Cervical Cancer Mortality Ratesa and Number of Cervical Cancer Deaths Among US Women Aged Younger Than 25 Years, 1992-2021
Trends in Cervical Cancer Mortality Ratesa and Number of Cervical Cancer Deaths Among US Women Aged Younger Than 25 Years, 1992-2021 (opens in new tab)
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Squares represent observed cervical cancer mortality rates per 100 000 women. Dashed line represents the cervical cancer modeled trends. Solid line represents the cervical cancer projected trends. Projected trends were estimated based on the trends from 1992-1994 to 2013-2015 continuing to 2019-2021. Data retrieved from the National Center for Health Statistics database.

aMortality rates were calculated as the number of deaths per 100 000 person-years and age-adjusted to the 2000 US population.

Discussion

This study found a steep decline in cervical cancer mortality among US women younger than 25 years between 2016 and 2021. This cohort of women is the first to be widely protected against cervical cancer by HPV vaccines. The findings from this study in the context of other published research2,3,5 suggest that HPV vaccination affected the sequential decline in HPV infection prevalence, cervical cancer incidence, and cervical cancer mortality. Since its introduction, HPV vaccination coverage (≥1 doses) has increased steadily, reaching 78.5% in 2021.5 The gradual decline in mortality observed from 1992 to 2015 was likely due to improved screening coverage and approaches.

Study limitations include the ecological nature of the analysis, the small number of cases in some years (since cervical cancer is rare in young women), and the lack of HPV vaccination status in cancer registry data, which precludes making any causal inference.

Since the beginning of the COVID-19 pandemic, HPV vaccination coverage has not improved and a troubling decline occurred (from 79.3% in 2022 to 75.9% in 2023) among the most recent generation of US adolescents.6 The findings from this study highlight the urgency to improve HPV vaccination coverage.

Section Editors: Kristin Walter, MD, and Jody W. Zylke, MD, Deputy Editors; Karen Lasser, MD, MPH, Senior Editor.
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Article Information

Accepted for Publication: October 3, 2024.

Published Online: November 27, 2024. doi:10.1001/jama.2024.22169

Corresponding Author: Ashish A. Deshmukh, PhD, MPH, Department of Public Health Sciences, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, Charleston, SC 29424 ([email protected]).

Author Contributions: Drs Dorali and Deshmukh had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Dorali and Damgacioglu are co–first authors.

Concept and design: Dorali, Damgacioglu, Orr, Deshmukh.

Acquisition, analysis, or interpretation of data: Dorali, Damgacioglu, Clarke, Wentzensen, Sonawane, Deshmukh.

Drafting of the manuscript: Dorali, Damgacioglu, Deshmukh.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Dorali, Damgacioglu, Wentzensen, Deshmukh.

Obtained funding: Sonawane, Deshmukh.

Administrative, technical, or material support: Deshmukh.

Supervision: Damgacioglu, Sonawane, Deshmukh.

Other: Sonawane.

Conflict of Interest Disclosures: Dr Sonawane reported receiving personal fees from Value Analytics Labs outside the submitted work. Dr Deshmukh reported receiving consulting fees from Value Analytics Labs and Merck outside the submitted work. No other disclosures were reported.

Funding/Support: Research reported in this publication was supported by the National Cancer Institute (P30CA138313, R01CA282424) and the National Institute on Minority Health and Health Disparities (K01MD016440) of the National Institutes of Health.

Role of the Funder/Sponsor: The National Cancer Institute and the National Institute on Minority Health and Health Disparities had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 1.

Additional Contributions: The authors gratefully thank Talia Wahl, MPH (Medical University of South Carolina), for her administrative support. She did not receive compensation.

References
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