Keywords
anal cancer - mortality - neoplasm
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]).
Table 1
Distribution of deaths from anal cancer by gender and year: (A) and (B) for women,
and (C) and (D) for men
|
(A)
|
Age range
|
2012
|
2013
|
2014
|
2015
|
2016
|
total deaths in the period 2012-2016
|
(B)
|
Age range
|
2017
|
2018
|
2019
|
2020
|
2021
|
total deaths in the period 2017-2021
|
|
20-29
|
1
|
0
|
0
|
2
|
1
|
4
|
|
20-29
|
3
|
5
|
2
|
1
|
6
|
17
|
|
30-39
|
6
|
9
|
9
|
4
|
7
|
35
|
|
30-39
|
11
|
8
|
16
|
10
|
18
|
63
|
|
40-49
|
25
|
17
|
19
|
13
|
27
|
101
|
|
40-49
|
23
|
29
|
43
|
44
|
43
|
182
|
|
50-59
|
44
|
50
|
51
|
64
|
46
|
255
|
|
50-59
|
62
|
77
|
84
|
123
|
96
|
442
|
|
60-69
|
57
|
57
|
44
|
60
|
77
|
295
|
|
60-69
|
69
|
90
|
122
|
146
|
148
|
575
|
|
70-79
|
48
|
68
|
54
|
56
|
60
|
286
|
|
70-79
|
62
|
102
|
128
|
141
|
149
|
582
|
|
80+
|
41
|
41
|
56
|
58
|
57
|
253
|
|
80+
|
61
|
82
|
105
|
124
|
138
|
510
|
|
(C)
|
Age range
|
2012
|
2013
|
2014
|
2015
|
2016
|
total deaths in the period 2012-2016
|
(D)
|
Age range
|
2017
|
2018
|
2019
|
2020
|
2021
|
total deaths in the period 2017-2021
|
|
20-29
|
4
|
1
|
0
|
0
|
0
|
5
|
|
20-29
|
0
|
1
|
2
|
3
|
2
|
8
|
|
30-39
|
4
|
7
|
10
|
7
|
9
|
37
|
|
30-39
|
8
|
6
|
10
|
18
|
17
|
59
|
|
40-49
|
15
|
16
|
22
|
14
|
23
|
90
|
|
40-49
|
20
|
26
|
37
|
51
|
37
|
171
|
|
50-59
|
25
|
26
|
37
|
35
|
34
|
157
|
|
50-59
|
33
|
48
|
86
|
104
|
101
|
372
|
|
60-69
|
35
|
24
|
15
|
31
|
33
|
138
|
|
60-69
|
32
|
52
|
100
|
119
|
149
|
452
|
|
70-79
|
24
|
22
|
24
|
31
|
24
|
125
|
|
70-79
|
43
|
43
|
92
|
91
|
111
|
380
|
|
80+
|
14
|
10
|
7
|
30
|
17
|
78
|
|
80+
|
32
|
34
|
66
|
65
|
86
|
283
|
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]).
Fig. 1 Annual crude mortality rate of anal cancer by gender in Brazil (deaths/100,000 inhabitants).
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]).
Table 2
Annual crude mortality rate of anal cancer by gender (deaths/100,000 inhabitants)
and female-to-male ratio of the annual mortality rate of anal cancer
|
Year
|
Female
|
Male
|
Female/male
|
|
2012
|
0,219
|
0,127
|
1,73
|
|
2013
|
0,237
|
0,108
|
2,19
|
|
2014
|
0,226
|
0,116
|
1,94
|
|
2015
|
0,248
|
0,149
|
1,67
|
|
2016
|
0,262
|
0,139
|
1,88
|
|
2017
|
0,275
|
0,167
|
1,65
|
|
2018
|
0,369
|
0,206
|
1,79
|
|
2019
|
0,466
|
0,382
|
1,22
|
|
2020
|
0,544
|
0,436
|
1,25
|
|
2021
|
0,548
|
0,482
|
1,14
|
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]).
Fig. 2 Female annual mortality rate stratified by age range (deaths/100,000 inhabitants).
Fig. 3 Male annual mortality rate stratified by age range (deaths/100,000 inhabitants).
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.
Fig. 4 Average annual percent change (AAPC) in mortality rate from anal cancer by age range
and gender in Brazil.
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.
Bibliographical Record
Camila Rafaela Lazaretti, Gilmara Coelho Meine. Trends in Mortality of Anal Cancer
in Brazil, 2012-2021. Journal of Coloproctology 2025; 45: s00451809674.
DOI: 10.1055/s-0045-1809674
