Trends in Mortality of Anal Cancer in Brazil, 2012-2021

• Abstract
• Introduction
• Methods
• Results
• Discussion
• Conclusion
• References

Abstract

Introduction

Anal cancer accounts for 2% of malignant neoplasms of the gastrointestinal tract, and squamous cell carcinoma is the most common histology. Its incidence and mortality have risen over the past four decades in different countries, concomitant with the increase in human papillomavirus (HPV) infection rates. Our objective was to analyze the trends in anal cancer mortality rates in Brazil from 2012 to 2021, with a focus on gender and age.

Methods

This descriptive study of anal cancer deaths (ICD-10 code C21) in Brazil utilized data from the Mortality Information System of the Unified Health System (DATASUS)

Results

From 2012 to 2021, the number of deaths from anal cancer was higher among women, and the number of anal cancer mortality rates increased in both sexes. Additionally, the average annual percent change (AAPC) in anal cancer mortality rates was higher in males than females across all age groups except for ages 30-39. In individuals aged 40 and over, the AAPC of anal cancer mortality rates increased progressively with age in males, while in females it remained stable across different age groups. As a result, the ratio between the female and male mortality rate decreased from 1.88 (2012-2016) to 1.41 (2017-2021), reaching its lowest value of 1.14 in 2021.

Conclusion

Despite its rarity, anal cancer warrants recognition due to its rising mortality rates. Initially, women experienced significantly higher mortality rates from anal cancer, but recent trends show a rapid increase among men, resulting in comparable mortality rates between genders by 2021.

Introduction

Anal cancer accounts for 2% of malignant neoplasms of the gastrointestinal tract, and squamous cell carcinoma is the most common histology. Its incidence and mortality have risen over the past four decades in different countries, concomitant with the increase in human papillomavirus (HPV) infection rates.[1] [2]

Individuals with human immunodeficiency virus (HIV) and HPV, especially HPV-16, are at an increased risk of developing anal cancer. This risk also extends to smokers, those with early sexual intercourse, individuals with multiple sexual partners, those who maintain receptive anal intercourse, and people with a history of HPV-mediated genital cancer.[3] [4] [5]

Although anal cancer is a rare type of neoplasm, it is crucial to recognize its significance due to the progressive rise in mortality rates, especially in Brazil. Therefore, the aim of this study was to analyze the evolution of anal cancer mortality rate in Brazil from 2012 to 2021, considering gender and age demographics.

Methods

The descriptive research analyzed deaths due to anal cancer (ICD 21) in Brazil from 2012 to 2021 from the Mortality Information System of the Department of Informatics of the Unified Health System (DATASUS),[6] considering the variables of gender and age.

We calculated the crude annual mortality rate by dividing the number of deaths (numerator) by the estimated population in the year (denominator) and reported it as the number of deaths per 100,000 inhabitants. The Brazilian Institute of Geography and Statistics (IBGE) provided the estimated population.[7] We also adjusted the annual mortality rate for age range and gender and calculated the annual percent change in mortality rate from anal cancer. The statistical analysis and graphs used in the study were developed in Microsoft Excel® 2016 spreadsheets.

Results

In Brazil, between 2012 and 2021, there were 5,955 deaths from anal cancer, with 3,600 occurring among women and 2,355 among men. Among women and men, the highest number of deaths occurred in the age groups above 50 years ([Table 1]).

There was a growing trend in the mortality rate of anal cancer throughout the evaluated period. In 2012, the mortality rate was 0.22 deaths per 100,000 women and 0.13 deaths per 100,000 men, which increased to 0.55 deaths per 100,000 women and 0.48 deaths per 100,000 men by 2021 ([Fig. 1]).

Upon assessing the ratio between the female and male crude mortality rates from anal cancer, we found that the mean ratio in the first five-year period was 1.88, decreasing to 1.41 in the last five-year period. The ratio reached its lowest value in 2021, dropping to 1.14 ([Table 2]).

Regarding the mortality rate from anal cancer by age range, it is noteworthy that it progressively increased with aging for both men and women across all the evaluated years, with the highest rates observed in the age group over 80 years ([Figs. 2] and [3]).

Furthermore, the average annual percent change (AAPC) in anal cancer mortality rates increased across all age ranges for both genders ([Fig. 4]). With population aging, there was a tendency for a higher AAPC in mortality rates from anal cancer among men compared to women. In the age range of 30-39 years, the AAPC in mortality rates was similar between genders, with a growth of 26% per year among women and 23% per year among men. However, for individuals aged 40 and over, the AAPC in anal cancer mortality rates increased progressively with age in males, while in females it remained stable across different age groups. Notably, for individuals over 80 years, the AAPC in mortality rates was significantly higher among men, with a growth of 44% per year compared to 11% per year among women.

Discussion

The results of the present analysis show that the crude mortality rate of anal cancer in Brazil almost tripled between 2012 and 2021. During this period, the mortality rate increased by 2.5-fold in women and nearly 4-fold in men, although it remained below 1 per 100,000.

A recently published study described that age-standardized mortality rates per 100,000 person-years have increased in the last decades in almost all countries and for both sexes.[2] Moreover, a study that aimed to assess sociodemographic disparities of anal cancer showed that the incidence continued to rise in men during the postvaccine era in the United States, and those communities with the highest proportion of poverty and racial/ethnic minority groups bore the highest burden of disease.[8]

Changes in sexual behavior patterns, such as increased unprotected sexual activity, a higher number of sexual partners, and a greater frequency of receptive anal intercourse in both men and women, may impact the incidence and mortality of anal cancer.

Additionally, population aging leads to longer exposure time to risk factors for anal cancer and may explain the progressively increased mortality rate of anal cancer with aging across all the evaluated years. The survival of HIV-infected patients significantly improved in the last two decades following advancements in HIV management, and the incidence of several HPV-related cancers is higher in people living with HIV (PLWH) despite the availability of effective antiretroviral therapy. Thus, the burden of persistent HPV-related disease has become a significant concern in an aging HIV population.[9]

Most anal cancer cases are caused by a high-risk infection with HPV.[10] This infection is the most common sexually transmitted infection worldwide. Although most HPV infections will spontaneously resolve, the clearance of HPV infection is less efficient in PLWH compared with the general population. The coinfection by HIV and HPV disproportionally affects men who have sex with men for whom the rate of persistent HPV infection and reinfection is noteworthy.[9] However, a German study reported that HIV-infected women also have a high rate of HPV in the anal canal (83.15%).[11]

The prophylactic effectiveness and safety of the HPV vaccine are established in both men and women.[12] An Italian study characterized the genotypes infecting the anal mucosa of HIV-positive and HIV-negative women and men and concluded that the nonavalent vaccine has the potential to prevent anal cancer and at least two-thirds of anal infections.[13] Since most anal cancer cases result from high-risk HPV infections, this cancer can be prevented through HPV vaccination.

In Brazil, the first vaccination campaign against HPV was launched in 2014, and the vaccine is provided free of charge through the public health system, targeting the most common types of HPV (6, 11, 16, and 18). It is recommended for (i) girls and boys aged 9 to 14 years; (ii) individuals aged between 9 and 45 years who are victims of sexual abuse and have not received the HPV vaccine or have an incomplete schedule; and (iii) individuals aged 9 to 45 years living with HIV, solid organ transplant recipients, bone marrow transplant recipients, or cancer patients.[14]

Conclusion

In conclusion, the mortality rate of anal cancer has been higher among women. From 2012 to 2021, Brazil saw an increase in the mortality rate of this neoplasm in both men and women, with a more pronounced rise among men, especially in older age groups. Consequently, the crude annual death rate from anal cancer approached parity between genders by 2021. Since most anal cancer cases result from high-risk HPV infections, it is imperative to raise awareness about the risks of anal HPV infection and the substantial benefits of vaccination.

Conflict of Interests

The authors have no competing interests to declare.

Author Contributions

Conceptualization: Camila Rafaela Lazaretti and Gilmara Coelho Meine

Methodology: Camila Rafaela Lazaretti and Gilmara Coelho Meine

Investigation: Camila Rafaela Lazaretti and Gilmara Coelho Meine

Writing – original draft: Camila Rafaela Lazaretti and Gilmara Coelho Meine

Writing – review & editing: Gilmara Coelho Meine

Supervision: Gilmara Coelho Meine

Ethics Committee Approval

An ethics committee approval was not needed as our study uses anonymized, publicly available secondary data from the Mortality Information System of the Department of Informatics of the Unified Health System (DATASUS), ensuring no risk to individual privacy or confidentiality.

• References

• 1 Gondal TA, Chaudhary N, Bajwa H, Rauf A, Le D, Ahmed S. Anal Cancer: The Past, Present and Future. Curr Oncol 2023; 30 (03) 3232-3250
  PubMedSearch in Google Scholar
• 2 Mignozzi S, Santucci C, Malvezzi M, Levi F, La Vecchia C, Negri E. Global trends in anal cancer incidence and mortality. Eur J Cancer Prev 2024; 33 (02) 77-86
  PubMedSearch in Google Scholar
• 3 Nelson VM, Benson III AB. Epidemiology of Anal Canal Cancer. Surg Oncol Clin N Am 2017; 26 (01) 9-15
  PubMedSearch in Google Scholar
• 4 Roberts JR, Siekas LL, Kaz AM. Anal intraepithelial neoplasia: A review of diagnosis and management. World J Gastrointest Oncol 2017; 9 (02) 50-61
  CrossrefPubMedSearch in Google Scholar
• 5 Itarat Y, Kietpeerakool C, Jampathong N. et al. Sexual behavior and infection with cervical human papillomavirus types 16 and 18. Int J Womens Health 2019; 11: 489-494
  PubMedSearch in Google Scholar
• 6 Ministério da Saúde. Sistema de Informações sobre Mortalidade (SIM) [Internet]. Accessed: 2024 Apr. 07 at: http://tabnet.datasus.gov.br/cgi/deftohtm.exe?sim/cnv/obt10uf.def
• 7 Instituto Brasileiro de Geografia e Estatística (IBGE). ( 2020 Projections of the Population of Brazil and Federative Units by sex and age: 2010-2060 (updated data). Accessed: 2024 Feb. 8 at: https://www.ibge.gov.br/estatisticas/sociais/populacao/9109-projecao-da-populacao.html
  Search in Google Scholar
• 8 Oliveira CR, Niu YS, Einarsdottir HM, Niccolai LM, Shapiro ED. Disparities in the Epidemiology of Anal Cancer: A Cross-Sectional Time Series. Health Equity 2020; 4 (01) 382-385
  PubMedSearch in Google Scholar
• 9 Pérez-González A, Cachay E, Ocampo A, Poveda E. Update on the Epidemiological Features and Clinical Implications of Human Papillomavirus Infection (HPV) and Human Immunodeficiency Virus (HIV) Coinfection. Microorganisms 2022; 10 (05) 1047
  PubMedSearch in Google Scholar
• 10 De Vuyst H, Clifford GM, Nascimento MC, Madeleine MM, Franceschi S. Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer 2009; 124 (07) 1626-1636
  CrossrefPubMedSearch in Google Scholar
• 11 Kost BP, Hofmann J, Stoellnberger S. et al. Prevalence of human papillomavirus infection of the anal canal in women: A prospective analysis of high-risk populations. Oncol Lett 2017; 13 (04) 2495-2501
  CrossrefPubMedSearch in Google Scholar
• 12 Șandru F, Radu AM, Petca A, Dumitrașcu MC, Petca RC, Roman AM. Unveiling the Therapeutic Horizon: HPV Vaccines and Their Impact on Cutaneous Diseases-A Comprehensive Review. Vaccines (Basel) 2024; 12 (03) 228
  PubMedSearch in Google Scholar
• 13 Fracella M, Oliveto G, Roberto P. et al. The Epidemiology of Anal Human Papillomavirus (HPV) in HIV-Positive and HIV-Negative Women and Men: A Ten-Year Retrospective Observational Study in Rome (Italy). Pathogens 2024; 13 (02) 163
  PubMedSearch in Google Scholar
• 14 Ministério da Saúde. . HPV. Accessed on: 2024 Apr. 07 at: < https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/h/hpv >

Address for correspondence

Publication History

Received: 11 August 2024

Accepted: 21 March 2025

Article published online:
26 June 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

Thieme Revinter Publicações Ltda.
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• References

• 1 Gondal TA, Chaudhary N, Bajwa H, Rauf A, Le D, Ahmed S. Anal Cancer: The Past, Present and Future. Curr Oncol 2023; 30 (03) 3232-3250
  PubMedSearch in Google Scholar
• 2 Mignozzi S, Santucci C, Malvezzi M, Levi F, La Vecchia C, Negri E. Global trends in anal cancer incidence and mortality. Eur J Cancer Prev 2024; 33 (02) 77-86
  PubMedSearch in Google Scholar
• 3 Nelson VM, Benson III AB. Epidemiology of Anal Canal Cancer. Surg Oncol Clin N Am 2017; 26 (01) 9-15
  PubMedSearch in Google Scholar
• 4 Roberts JR, Siekas LL, Kaz AM. Anal intraepithelial neoplasia: A review of diagnosis and management. World J Gastrointest Oncol 2017; 9 (02) 50-61
  CrossrefPubMedSearch in Google Scholar
• 5 Itarat Y, Kietpeerakool C, Jampathong N. et al. Sexual behavior and infection with cervical human papillomavirus types 16 and 18. Int J Womens Health 2019; 11: 489-494
  PubMedSearch in Google Scholar
• 6 Ministério da Saúde. Sistema de Informações sobre Mortalidade (SIM) [Internet]. Accessed: 2024 Apr. 07 at: http://tabnet.datasus.gov.br/cgi/deftohtm.exe?sim/cnv/obt10uf.def
• 7 Instituto Brasileiro de Geografia e Estatística (IBGE). ( 2020 Projections of the Population of Brazil and Federative Units by sex and age: 2010-2060 (updated data). Accessed: 2024 Feb. 8 at: https://www.ibge.gov.br/estatisticas/sociais/populacao/9109-projecao-da-populacao.html
  Search in Google Scholar
• 8 Oliveira CR, Niu YS, Einarsdottir HM, Niccolai LM, Shapiro ED. Disparities in the Epidemiology of Anal Cancer: A Cross-Sectional Time Series. Health Equity 2020; 4 (01) 382-385
  PubMedSearch in Google Scholar
• 9 Pérez-González A, Cachay E, Ocampo A, Poveda E. Update on the Epidemiological Features and Clinical Implications of Human Papillomavirus Infection (HPV) and Human Immunodeficiency Virus (HIV) Coinfection. Microorganisms 2022; 10 (05) 1047
  PubMedSearch in Google Scholar
• 10 De Vuyst H, Clifford GM, Nascimento MC, Madeleine MM, Franceschi S. Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer 2009; 124 (07) 1626-1636
  CrossrefPubMedSearch in Google Scholar
• 11 Kost BP, Hofmann J, Stoellnberger S. et al. Prevalence of human papillomavirus infection of the anal canal in women: A prospective analysis of high-risk populations. Oncol Lett 2017; 13 (04) 2495-2501
  CrossrefPubMedSearch in Google Scholar
• 12 Șandru F, Radu AM, Petca A, Dumitrașcu MC, Petca RC, Roman AM. Unveiling the Therapeutic Horizon: HPV Vaccines and Their Impact on Cutaneous Diseases-A Comprehensive Review. Vaccines (Basel) 2024; 12 (03) 228
  PubMedSearch in Google Scholar
• 13 Fracella M, Oliveto G, Roberto P. et al. The Epidemiology of Anal Human Papillomavirus (HPV) in HIV-Positive and HIV-Negative Women and Men: A Ten-Year Retrospective Observational Study in Rome (Italy). Pathogens 2024; 13 (02) 163
  PubMedSearch in Google Scholar
• 14 Ministério da Saúde. . HPV. Accessed on: 2024 Apr. 07 at: < https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/h/hpv >