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Racial/ethnic disparities in HPV-
associated anogenital cancers among 
males in the United States: a population-
based retrospective cohort study 
Seiichi Villalona1, Simone Sukhdeo1, Daisy Reinoso1, Antoinette M. Stroup2,3, Jeanne M. Ferrante3,4* 

1 Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA 
2 Department of Biostatistics & Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA 
3 Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA 
4 Department of Family Medicine and Community Health, Rutgers Robert Wood Johnson Medical School, 
New Brunswick, NJ, USA 

*Corresponding author: Jeanne M. Ferrante, Email: jeanne.ferrante@rutgers.edu 

ABSTRACT 
Little is known regarding racial/ethnic differences in human papillomavirus (HPV)-associated anogenital 
cancer among males. This population-based retrospective cohort study included 39,601 males diagnosed 
with HPV-associated invasive penile and anorectal cancers between 2005-2016 from the North American 
Association of Central Cancer Registries. We evaluated the association of race/ethnicity with late-stage 
diagnosis, survival, and mortality of anogenital cancers among males in the United States using 
multivariable logistic regression and Cox proportional hazard models. Hispanic and Non-Hispanic (NH) 
Black males had highest age-adjusted incidence of penile and anorectal cancer, respectively. Higher odds 
of late-stage penile cancer were observed among NH Black (adjusted odds ratios [aOR] 1.22, 95% CI 1.07-
1.39) and Hispanic males (aOR 1.17, 95% CI 1.04-1.31). Higher odds of late-stage anorectal cancer were 
observed among NH Black (aOR 1.25, 95% CI 1.14-1.36) and NH Other males (aOR 1.29, 95% CI 1.01-1.66). 
Compared to all other groups, NH Black males had the lowest cumulative and mean survival of both 
cancers and higher cancer-specific mortality (penile adjusted hazards ratios [aHR] 1.23, 95% CI 1.01-1.49; 
anorectal aHR 1.25, 95% CI 1.10-1.42). There are different racial/ethnic disparities in health outcomes 
among males depending on site of HPV-associated anogenital cancer. Interventions to increase HPV 
vaccination rates, early detection, and treatment of anogenital cancers in males are needed, particularly 
among men of color. 

KEYWORDS: Human Papillomavirus (HPV), anorectal cancer, penile cancer, males, racial/ethnic 
disparities. 

Citation: Villalona S et al (2022) Racial/ethnic disparities in HPV-associated anogenital cancers among males 
in the United States: a population-based retrospective cohort study. Cancer Health Disparities 6:e1-25. 
doi:10.9777/chd.2022.1006 



 
 
 
 
 

 
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INTRODUCTION 
Human papillomavirus (HPV)-associated cancers 
have become an increasing healthcare burden, 
accounting for over 46,000 cancer cases per year in 
the United States (Centers for Disease Control and 
Prevention, 2021). HPV infection often precedes the 
development of anogenital (AG) cancers, with 
approximately 64% of penile cancers and 91% of 
anal cancers attributable to HPV, particularly from 
oncogenic strains 16 and 18 (Centers for Disease 
Control and Prevention, 2021). In 2022, there will be 
an estimated 2,070 and 3150 new cases of penile 
and anorectal cancers, respectively, among males 
in the U.S.(Siegel et al., 2022). While incidence of 
cervical cancer has been declining in females due 
to widespread use of Papanicolaou smears, there 
has been a steady increase in HPV-associated 
cancers among males over the last few decades 
(Liao et al., 2022), highlighting the importance of 
targeting male HPV-associated AG cancer in public 
health efforts. 

Penile cancer comprises 0.2% of male-associated 
malignancies (Siegel et al., 2022), with higher 
incidences observed in Hispanic and NH Black 
males (Attalla et al., 2018; Sharma et al., 2016b). One 
potential risk factor for HPV-associated penile 
cancer is lack of circumcision. The Human 
Papillomavirus Infection in Men (HIM) study 
reported that circumcision was associated with 
reduced risk of HPV detection across all viral strains 
tested (Giuliano et al., 2010; Giuliano et al., 2009). 
Cultural differences in circumcision practice can 
create populations at greater risk for HPV infection 
and subsequent penile cancer. In the U.S., Hispanic 
males have lower rates of circumcision relative to 
other ethnic groups, which may shift the healthcare 
burden of penile cancer disproportionately on the 
male Hispanic population (Colón-López et al., 
2010). Additional risk factors such as lack of 
insurance, lower education, and lower 

socioeconomic status (SES) may result in poorer 
prognosis and worse survival among Hispanic 
males (Attalla et al., 2018; Sharma et al., 2016a). 

Anal cancer incidence is rising among men (annual 
increase of 1.2%) while declining among women 
(3.2% annual decrease) (Centers for Disease Control 
and Prevention, 2020). Notably, new cases are 
highest in NH Black males with an annual average 
percentage increase of 3.40% between 2001-2017, 
and studies have shown poorer survival outcomes 
in this population (Benard et al., 2008; Fields et al., 
2019; Liao et al., 2022; Patel et al., 2020). It has been 
suggested that the rising incidence of anal cancer 
parallels a rising incidence of HIV infection in racial 
minority populations and men who have sex with 
men (MSM) due to HIV and HPV co-infection 
(Walsh et al., 2015; Ye et al., 2020). However, the 
trends in incidence of anal cancer and poorer 
survival in NH Black males most likely result from a 
combination of socioeconomic status, insurance, 
and treatment factors, in addition to sexual 
practices and HIV status (Bian et al., 2021; Fields et 
al., 2019; Gillis et al., 2020; Goksu et al., 2020). 

Prior studies of HPV-associated cancers in men 
have focused on select subpopulations (e.g. HIV-
positive men) or limited the inclusion of distinct 
minority groups. However, a more encompassing 
sample is necessary to explore the intersections of 
race/ethnicity, HPV-associated cancer incidence 
and outcomes, and social determinants of health 
(Baughman and Shah, 2016; Bojko et al., 2018; 
Goksu et al., 2020; Gupta et al., 2017; Ortiz et al., 
2018; Walsh et al., 2015). In this present study, we 
compared differences in stage at diagnosis, survival, 
and mortality of AG cancers in males among 
different racial/ethnic groups, while controlling for 
age, area poverty level, area of residence, and 
insurance status, all factors previously suggested to 
impact survival in males with AG cancers (Attalla et 
al., 2018; Bojko et al., 2018). To our knowledge, this 



 
 
 
 
 

 
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is the largest population-based study to examine 
racial/ethnic disparities in incidence, late-stage 
diagnosis, survival and mortality of AG cancers 
among males across the U.S. Identifying 
populations at risk is important to understand which 
men to target preventive interventions. 

MATERIALS AND METHODS 
Data and Sample 
This is a population-based retrospective cohort 
study of males in the U.S. diagnosed with invasive 
anogenital (AG) cancers between 2005-2016 within 
the North American Association of Central Cancer 
Registries (NAACCR) Cancer in North America 
(CiNA) Deluxe data file (North American Association 
of Central Cancer Registries, 2018). NAACCR CiNA 
is the most comprehensive cancer incidence 
database, covering 93% of the U.S. population, and 
it includes all 18 Surveillance, Epidemiology, and 
End Results (SEER) registries. The database contains 
de-identified demographic, cancer type, and 
treatment information from population-based 
cancer registries across the U.S. and Canada. For 
survival and mortality analyses, we used a subset of 
this data file, the CiNA Survival dataset, which 
includes cancer registries that meet the 
Surveillance, Epidemiology, and End Results (SEER) 
standards for follow-up or ascertainment of deaths. 
Data were accessed through the SEER*Stat software 
program and exported into the Statistical Package 
for the Social Sciences (SPSS) version 27 (IBM, 
Armonk, New York) for advanced analyses. This 
study was approved by the Institutional Review 
Boards at NAACCR and Rutgers, the State 
University of New Jersey. 

We included males with tumors in the following 
anatomical sites under the International 
Classification of Diseases for Oncology (ICD-O)-3: 
rectum (C20.9); anus (C21.0); anal canal (C21.1); 
cloacogenic zone (C21.2); overlapping lesion of 
rectum, anus, and anal canal (C21.8); prepuce 

(C60.0); glans penis (C60.1); body of penis (C60.2); 
overlapping lesion of penis (C60.8); and penis 
(C60.9) for a total of 263,102 individual cases. We 
excluded persons <15 years of age (n=28); cases 
diagnosed at autopsy or by death certificate 
(n=1,538); and diagnosis in Puerto Rico (n=2,268). 
Because cancer registries do not collect HPV status 
of cancers, we used standard Centers for Disease 
Control and Prevention definitions of HPV-
associated cancers, i.e., ICD-O-3 site codes (listed 
above) and histological codes (squamous cell 
carcinoma (SCC) 8050-8084; 8120-8131) to identify 
HPV-associated AG cancers (Centers for Disease 
Control and Prevention, 2020). HPV-associated AG 
cancers were restricted to microscopically 
confirmed cases. 

Stage at Diagnosis  
Stage at diagnosis was classified as local, regional, 
and distant based on the SEER Summary Stage 
1977/2000/Derived variable. For the stage at 
diagnosis analyses, we excluded persons with 
unknown stage (n=21,212), resulting in a final 
analytic sample of 39,601 cases. We defined stage 
as “early” if the AG cancer was diagnosed with local 
stage disease, and “late” if the AG cancer was 
diagnosed with regional or distant stage disease 
(Yang et al., 2018). 

Survival and Mortality 
We excluded cases diagnosed after December 31, 
2011 (n=67,720) for our survival and mortality 
analyses in order to have at least 5 years of follow-
up. We also excluded cases where AG cancer was 
not the first primary malignancy (N=44,196), had 
unknown cause of death (N=9,165), or unknown 
survival time (N=18,149), resulting in a final analytic 
sample of 15,244 cases. Mean cancer-specific 
survival for each racial/ethnic group was generated 
within SEER*Stat using the actuarial method (Ohno-
Machado, 2001), via the “SEER cause-specific death 
classification” variable from the NAACCR data file 



 
 
 
 
 

 
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(North American Association of Central Cancer 
Registries, 2018). This variable takes into account 
cause of death information (ICD-10 codes), site of 
original cancer diagnosis, tumor sequence, and 
diseases associated to the cancer of diagnosis, and 
it addresses known misclassifications in cause of 
death on death certificates for cancer (Howlader et 
al., 2010). Cases are categorized as: dead 
(attributable to this cancer diagnosis); alive or dead 
of other cause; and dead (missing/unknown cause 
of death) (Howlader et al., 2010). In cancer-specific 
mortality analyses, persons who died of causes 
other than AG cancer were censored.  

Covariates 
The main independent variable of interest, 
race/ethnicity, was based on self-report and 
categorized as NH White, NH Black, Hispanic, and 
NH Other (Asians/Pacific Islanders and American 
Indians/Alaskan Natives) as classified in the 
NAACCR Research File (North American 
Association of Central Cancer Registries, 2018). 
Other covariates considered in our analyses 
included: age at diagnosis, health insurance, county 
level attributes of residence (Metropolitan/Non-
metropolitan, percent of persons below poverty), 
geographic region of the U.S., and treatment 
modality. The NAACCR CiNA Research file 
categorizes age at diagnosis in 5-year intervals (e.g. 
35-39, 40-44). We grouped this into three 
categories: <54, 55-64, 65+ years. Health insurance 
categories included: private, Medicare, Medicaid, 
Other (Indian/Public Health Service, Military, 
TRICARE, Veterans Affairs, and insurance not 
otherwise specified), and no insurance or self-pay. 
Metropolitan/Non-metropolitan county 
designations were broadly based on population 
size (metropolitan has 50,000 persons or more). 
Percent of persons below poverty was categorized 
as: <9.99%, 10-19.99%, and 20% or more below 
federal poverty levels. The four geographic regions 

of the U.S. were based on the U.S. Census Bureau: 
Northeast, South, Midwest, and West/Pacific 
(United States Census Bureau, 2018). Treatment 
modality included the first course of planned 
treatment and was categorized as: surgery only; 
radiation or chemotherapy only; surgery plus 
(radiation or chemotherapy); radiation and 
chemotherapy; all modalities; or no treatment. 

Statistical Analysis 
The number of new cases of HPV-associated AG 
cancer from 2005-2016 was extracted from 
SEER*Stat. Age-adjusted incidence rates, stratified 
by disease stage, anatomic site (penile or 
anorectal), and race/ethnicity were calculated 
directly from SEER*Stat. Bivariate relationship 
between demographic characteristics and late-
stage diagnosis was evaluated using χ2 tests and 
univariate logistic regression. Adjusted odds ratios 
(aOR) of late-stage diagnosis compared with early 
stage and corresponding 95% confidence intervals 
(CIs) were calculated for each category of 
race/ethnicity using multivariable logistic 
regression, adjusting for age at diagnosis, 
insurance, metropolitan/non-metropolitan 
residence, area poverty, and geographic region. 
Finally, interaction terms were included in our final 
model to examine how race/ethnicity modified the 
relationship between covariates and late-stage AG 
diagnosis.  

We used Cox proportional hazards regression to 
generate adjusted cancer-specific survival curves 
for different racial/ethnic groups. We examined 
associations of race/ethnicity with mortality from 
AG cancers using Cox proportional regression 
models to estimate the hazards of death from AG 
cancer (with 95% CIs). We included the variables 
described above and stage at diagnosis as potential 
confounders in multivariable model 1. To determine 
the effect of treatment modality on the associations 
between race/ethnicity and AG cancer mortality, we 



 
 
 
 
 

 
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added treatment to multivariable model 2. Finally, 
to examine potential effect modification of 
race/ethnicity on the other variables, interaction 
terms were included in the final multivariable model 
2. 

We conducted initial sensitivity analyses including 
and excluding cases with unknown race/ethnicity 
and unknown covariates. We additionally 
conducted sensitivity analyses of AG cancers as an 
aggregate sample and then stratified by anatomic 
site (penile and anorectal). Results were similar with 
and without unknown race and other covariates, 
but different when stratified by anatomic site. 
Therefore, we present multivariable models 
excluding missing values and separately for penile 
and anorectal cancers. 

RESULTS 
Table 1 describes the characteristics of our study 
cohort stratified by race/ethnicity. Most of our study 

sample consisted of NH White males (75%), aged 
65+ (43.1%), residing in large metropolitan areas 
(82.3%), covered by Medicare insurance (38.2%), 
living in counties with 10-19.99% poverty (69.2%), 
residing in the geographic South (38.6%), and with 
local disease stage at diagnosis (52.6%). A majority 
of the cases were anorectal cancers (63.1%). 
Compared to other racial/ethnic groups, a higher 
proportion of Hispanics (44.1%) and NH Black 
(52.2%) males were less than 54 years of age. 
Higher proportions of Hispanic (23.1%) and NH 
Black (22.6%) males had Medicaid or no health 
insurance. NH Black males represented the largest 
proportion of individuals living in counties with 
>20% of poverty (30.2%). Hispanic (56.2%) and NH 
Other (55.3%) males represented larger 
proportions of penile cancers, while NH Black males 
(70.7%) represented the highest proportion of 
anorectal cancers. All bivariate relationships were 
statistically significant using χ2 tests (all p-values 
<0.01). 

Table 1. Characteristics of HPV-associated anogenital cancers in males, United States, 2005-2016 (N = 39,601). 

Characteristic* Total 
N (%) 

Hispanic 
N (%) 

White NH 
N (%) 

Black NH 
N (%) 

Other, NH§ 

N (%) 
Unknown 

N (%) 

Overall 39,601 (100) 3,806 (9.6) 29,714 (75.0) 5,066 (12.8) 740 (1.9) 275 (0.7) 

Age at diagnosis, years 

 <54 12,436 (31.4) 1,679 (44.1) 7,772 (26.2) 2,643 (52.2) 224 (30.3) 118 (42.9) 

 55-64 10,089 (25.5) 883 (23.2) 7,761 (26.1) 1,182 (23.3) 195 (26.4) 68 (24.7) 

 65+ 17,076 (43.1) 1,244 (32.7) 14,181 (47.7) 1,241 (24.5) 321 (43.4) 89 (32.4) 

Residence 

 Metropolitan 32,572 (82.3) 3,558 (93.5) 23,518 (79.1) 4,629 (91.4) 634 (85.7) 233 (84.7) 

 Non-metropolitan 6,419 (16.2) 232 (6.1) 5,633 (19.0) 425 (8.4) 96 (13.0) 33 (12.0) 

 Unknown 610 (1.5) 16 (0.4) 563 (1.9) 12 (0.2) 10 (1.4) 9 (3.3) 

Insurance Status 

 Private 8,748 (22.1) 829 (21.8) 6,818 (22.9) 895 (17.7) 168 (22.7) 38 (13.8) 

 Medicare 15,123 (38.2) 1,030 (27.1) 12,185 (41.0) 1,596 (31.5) 254 (34.3) 58 (21.1) 



 
 
 
 
 

 
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 Medicaid 3,235 (8.2) 484 (12.7) 1,914 (6.4) 754 (14.9) 72 (9.7) 11 (4.0) 

 Other♦ 3,530 (8.9) 280 (7.4) 2,719 (9.2) 434 (8.6) 67 (9.1) 30 (10.9) 

 No Insurance/Self-Pay 2,097 (5.3) 397 (10.4) 1,261 (4.2) 388 (7.7) 39 (5.3) 12 (4.4) 

 Unknown 6,868 (17.3) 786 (20.7) 4,817 (16.2) 999 (19.7) 140 (18.9) 126 (45.8) 

% Persons Below Poverty at Residence 

 < 9.9% 5,312 (13.4) 314 (8.3) 4,408 (14.8) 407 (8.0) 141 (19.1) 42 (15.3) 

 10-19.99% 27,396 (69.2) 2,738 (71.9) 20,873 (70.2) 3,115 (61.5) 481 (65.0) 189 (68.7) 

 ≥ 20% 6,283 (15.9) 738 (19.4) 3,870 (13.0) 1,532 (30.2) 108 (14.6) 35 (12.7) 

 Unknown 610 (1.5) 16 (0.4) 563 (1.9) 12 (0.2) 10 (1.4) 9 (3.3) 

Geographic Region 

 Northeast 7,603 (19.2) 838 (22.0) 5,614 (18.9) 968 (19.1) 128 (17.3) 55 (20.0) 

 South 15,267 (38.6) 1,375 (36.1) 11,042 (37.2) 2,625 (51.8) 151 (20.4) 74 (26.9) 

 Midwest 8,172 (20.6) 247 (6.5) 6,815 (22.9) 975 (19.2) 88 (11.9) 47 (17.1) 

 West/Pacific 8,559 (21.6) 1,346 (35.4) 6,243 (21.0) 498 (9.8) 373 (50.4) 99 (36.0) 

Stage at Diagnosis 

 Local 20,814 (52.6) 1,970 (51.8) 15,921 (53.6) 2,408 (47.5) 374 (50.5) 141 (51.3) 

 Regional 12,574 (38.6) 1,255 (33.0) 9,207 (31.0) 1,811 (35.7) 247 (33.4) 54 (19.6) 

 Distant 3,025 (7.6) 266 (7.0) 2,241 (7.5) 443 (8.7) 64 (8.6) 11 (4.0) 

 Unknown 3,188 (8.1) 315 (8.3) 2,345 (7.9) 404 (8.0) 55 (7.4) 69 (25.1) 

Anatomical Site 

 Penile 14,612 (36.9) 2,140 (56.2) 10,477 (35.3) 1,482 (29.3) 409 (55.3) 104 (37.8) 

 Anorectal 24,989 (63.1) 1,666 (43.8) 19,237 (64.7) 3,584 (70.7) 331 (44.7) 171 (62.2) 

Treatment       

 Surgery Only 15,431 (39.0) 1,940 (51.0) 11,251 (37.9) 1,745 (34.4) 375 (50.7) 120 (43.6) 

 Radiation or Chemo 2,472 (6.2) 164 (4.3) 1,906 (6.4) 357 (7.0) 29 (3.9) 16 (5.8) 

 Surgery + (Radiation or 
Chemo) 

3,834 (9.7) 411 (10.8) 2,801 (9.4) 532 (10.5) 73 (9.9) 17 (6.2) 

 Radiation + Chemo 9,556 (24.1) 604 (15.9) 7,533 (25.4) 1,245 (24.6) 132 (17.8) 42 (15.3) 

 All Modalities 4,740 (12.0) 347 (9.1) 3,620 (12.2) 701 (13.8) 63 (8.5) 9 (3.3) 

 No Treatment 3,553 (9.0) 338 (8.9) 2,590 (8.7) 486 (9.6) 68 (9.2) 71 (25.8) 

NH, Non-Hispanic. Chemo, Chemotherapy. 

* All variables were statistically significant at p < 0.01 in bivariate analyses using χ2 tests. 
§ Includes Asian, American Indian, Alaska Native, and Pacific Islander  



 
 
 
 
 

 
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♦Other insurance includes Indian/Public Health Service, Military, TRICARE, Veterans Affairs, and insurance not otherwise specified. 

Figure 1 describes the age-adjusted incidence rates of HPV-associated AG cases from 2005-2016 by 
race/ethnicity and stage, stratified by anatomic site. The incidence rate of penile cancer remained relatively 
stable for all groups, while there were slight increases in late stage anorectal cancers among NH Black and 
NH White males. Relative to the other groups, Hispanics had the highest incidence rate of penile cancers 
irrespective of disease stage (1A, 1B), while NH Black males had the highest incidence rate of anorectal 
cancers (1C, 1D).  

Figure 1: Incidence of HPV-Associated Anogenital Cancers by Stage among Males, 2005-2016 
 (N= 36,413)† 

 
†Cases with unknown tumor stage were excluded. 

Stage at Anogenital Cancer Diagnosis 
Males with anorectal cancers had higher odds of 
late-stage diagnosis (aOR 1.32, 95% CI 1.26-1.39) 
relative to penile cancers (data not shown). Table 2 
describes factors associated with late stage 
diagnosis of penile and anorectal cancers. 
Compared to NH White males, higher odds of late-
stage penile cancers were observed in NH Black 
(aOR 1.22, 95% CI 1.07-1.39) and Hispanic males 
(aOR 1.17, 95% CI 1.04-1.31). Other independent 
factors associated with late-stage diagnosis of 

penile cancer included having Medicaid (aOR 1.50, 
95% CI 1.28-1.76) or no insurance (aOR 1.54, 95% CI 
1.30-1.82).  

Among anorectal cancers, NH Other (aOR 1.29, 
95% CI 1.01-1.66) and NH Black males (aOR 1.25, 
95% CI 1.14-1.36) had higher odds of late-stage 
diagnosis relative to NH White males. Additionally, 
males older than 55 years (55-64: aOR 1.17, 95% CI 
1.08-1.25; 65+: aOR 1.10, 95% CI 1.01-1.19), as well as 
those with Medicaid (aOR 1.62, 95% CI 1.46-1.79), 
other (aOR 1.12, 95% CI 1.02-1.24), or no 



 
 
 
 
 

 
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insurance/self pay (aOR 1.76, 95% CI 1.55-2.00) had 
higher odds of late-stage anorectal cancer 
diagnosis. Residential characteristics 

(metropolitan/non-metropolitan, area poverty, and 
geographic region) were not associated with late 
stage diagnosis of penile or anorectal cancers. 

 

Table 2. Predictors of Late Stage HPV-Associated Anogenital Cancers among Males in the United States, 
2005-2016 (N= 30,319)† 

Characteristic Penile Cancers (n=11,533) Anorectal Cancers (n=18,786) 

Race/Ethnicity aOR# (95% CI) aOR# (95% CI) 

 NH, White 1.00 1.00 

 Hispanic/Latino 1.17 (1.04, 1.31)* 0.94 (0.83, 1.06) 

 NH, Black 1.22 (1.07, 1.39)* 1.25 (1.14, 1.36)* 

 NH, Other§ 1.11 (0.88, 1.40) 1.29 (1.01, 1.66)* 

Age at diagnosis (years) 

 < 54  1.00 1.00 

 55-64 1.11 (0.99, 1.26) 1.17 (1.08, 1.25)* 

 65 + 0.91 (0.80, 1.04) 1.10 (1.01, 1.19)* 

Insurance Type 

 Private 1.00 1.00 

 Medicare 1.12 (0.99, 1.26) 1.01 (0.93, 1.09) 

 Medicaid 1.50 (1.28, 1.76)* 1.62 (1.46, 1.79)* 

 Other♦ 0.98 (0.84, 1.14) 1.12 (1.02, 1.24)* 

 No Insurance/Self Pay 1.54 (1.30, 1.82)* 1.76 (1.55, 2.00)* 

Residence  

 Large Metropolitan 1.00 1.00 

 Non-Metropolitan 0.97 (0.87, 1.06) 1.01 (0.93, 1.10) 

% Persons below Poverty at Residence 

 < 9.9% 1.00 1.00 

 10-19.99% 0.98 (0.88, 1.10) 1.01 (0.92, 1.10) 

 > 20% 0.92 (0.80, 1.07) 1.00 (0.89, 1.12) 

Geographic Region 

 Northeast 1.00 1.00 

 South 0.96 (0.85, 1.08) 1.03 (0.93, 1.13) 

 Midwest 1.01 (0.88, 1.15) 0.97 (0.88, 1.08) 

 West/Pacific 1.04 (0.91, 1.18) 1.07 (0.96, 1.18) 

HPV, human papillomavirus; NH, Non-Hispanic; aOR, adjusted odds ratio; CI, confidence interval  
† Cases with unknown stage and unknown covariates were excluded.  



 
 
 
 
 

 
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# Adjusted for all other variables in table 
* p ≤0.01 
§ Includes Asian, American Indian, Alaska Native, and Pacific Islander  
♦Other insurance includes Indian/Public Health Service, Military, TRICARE, Veterans Affairs, and insurance not otherwise specified. 

In interaction analyses for penile cancers, 
race/ethnicity modified the relationship between 
late-stage diagnosis and other factors 
(Supplemental Table 1). Compared with their NH 
White counterparts of the same age group, 
Hispanic males under the age of 55 (aOR 1.51, 95% 
CI 1.26-1.80) and NH Black males aged 65 and older 
(aOR 1.77, 95% CI 1.20-2.61) had higher odds of 
late-stage diagnosis. NH Black males with private 
insurance, living in large metropolitan or low 
poverty (<10% of population below poverty) areas, 
or who lived in the South or Western/Pacific regions 
were also found to have higher odds of late-stage 
diagnosis compared to NH White males. 

Additionally, Hispanic males were found to have 
higher odds of late-stage diagnosis when living in 
large metropolitan or low poverty areas and in the 
Western/Pacific region. Interestingly, NH Black 
males living in high poverty areas (>20% of 
population below poverty) had significantly lower 
odds of late-stage penile cancer compared to NH 
White males (aOR 0.55, 95% CI 0.32-0.95). For 
anorectal cancer, the only significant finding was 
that NH Other males aged 65 years and older were 
observed to have over 3 times higher odds of late-
stage diagnosis (aOR 3.01, 95% CI 1.50-6.02) relative 
to NH White males in the same age group (results 
not shown).  

Supplemental Table 1: Interactions of Race/Ethnicity with Covariates, Late-Stage Diagnosis from HPV-
Associated Penile Cancers among Males in the United States, 2005-2016 (N=11,533) † 

Characteristic aOR (95% CI) p-value 

Age at diagnosis (years)  0.01 

 < 54    

     NH, White 1.00  

     Hispanic/Latino 1.51 (1.26, 1.80) <0.01 

     NH, Black 1.08 (0.85, 1.36) 0.53 

     NH, Other§ 1.41 (0.90, 2.21) 0.13 

 55-64   

     NH, White 1.00  

     Hispanic/Latino 1.05 (0.77, 1.44) 0.74 

     NH, Black 1.21 (0.84, 1.74) 0.30 

     NH, Other 0.75 (0.36, 1.56) 0.45 

 65 +   

     NH, White 1.00  

     Hispanic/Latino 0.73 (0.52, 1.02) 0.06 

     NH, Black 1.77 (1.20, 2.62) <0.01 

     NH, Other 0.80 (0.38, 1.69) 0.56 



 
 
 
 
 

 
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Insurance Type  0.67 

 Private   

     NH, White 1.00  

     Hispanic/Latino 1.14 (0.91, 1.41) 0.25 

     NH, Black 1.37 (1.02, 1.83) 0.03 

     NH, Other 1.08 (0.70, 1.67) 0.71 

 Medicare   

     NH, White 1.00  

     Hispanic/Latino 1.16 (0.82, 1.63) 0.40 

     NH, Black 0.70 (0.47, 1.04) 0.08 

     NH, Other 1.21 (0.59, 2.51) 0.60 

 Medicaid   

     NH, White 1.00  

     Hispanic/Latino 1.12 (0.76, 1.66) 0.57 

     NH, Black 0.88 (0.54, 1.43) 0.60 

     NH, Other 0.74 (0.32, 1.69) 0.48 

 Other♦   

     NH, White 1.00  

     Hispanic/Latino 1.20 (0.78, 1.84) 0.41 

     NH, Black 0.87 (0.53, 1.44) 0.59 

     NH, Other 1.67 (0.65, 4.34) 0.29 

 No Insurance/Self Pay   

     NH, White 1.00  

     Hispanic/Latino 1.28 (0.86, 1.90) 0.23 

     NH, Black 0.73 (0.43, 1.22) 0.23 

     NH, Other 1.10 (0.39, 3.12) 0.86 

Residence   0.27 

 Large Metropolitan   

     NH, White 1.00  

     Hispanic/Latino 1.31 (1.19, 1.46) <0.01 

     NH, Black 1.25 (1.11, 1.42) <0.01 

     NH, Other 1.20 (0.95, 1.50) 0.12 

 Non-Metropolitan   

     NH, White 1.00  

     Hispanic/Latino 1.10 (0.74, 1.65) 0.64 

     NH, Black 1.40 (0.96, 2.06) 0.08 



 
 
 
 
 

 
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     NH, Other 0.73 (0.34, 1.57) 0.42 

% Persons below Poverty at Residence  0.14 

 < 9.9%   

     NH, White 1.00  

     Hispanic/Latino 1.51 (1.11, 2.07) 0.01 

     NH, Black 1.68 (1.13, 2.50) 0.01 

     NH, Other 1.31 (0.80, 2.14) 0.29 

 10-19.99%   

     NH, White 1.00  

     Hispanic/Latino 0.87 (0.59, 1.28) 0.48 

     NH, Black 0.62 (0.38, 1.00) 0.05 

     NH, Other 0.96 (0.50, 1.84) 0.91 

 > 20%   

     NH, White 1.00  

     Hispanic/Latino 0.77 (0.48, 1.22) 0.27 

     NH, Black 0.55 (0.32, 0.95) 0.03 

     NH, Other 1.29 (0.52, 3.23) 0.58 

Geographic Region  0.02 

 Northeast   

     NH, White 1.00  

     Hispanic/Latino 1.12 (0.89, 1.39) 0.33 

     NH, Black 1.07 (0.80, 1.42) 0.64 

     NH, Other 1.34 (0.85, 2.10) 0.21 

 South   

     NH, White 1.00  

     Hispanic/Latino 1.01 (0.55, 1.88) 0.97 

     NH, Black 1.78 (1.10, 2.89) 0.02 

     NH, Other 1.65 (0.96, 2.82) 0.07 

 Midwest   

     NH, White 1.00  

     Hispanic/Latino 0.83 (0.40, 1.73) 0.62 

     NH, Black 0.49 (0.20, 1.22) 0.12 

     NH, Other 1.29 (0.49, 3.40) 0.60 

 West/Pacific   

     NH, White 1.00  

     Hispanic/Latino 1.53 (1.05, 2.24) 0.03 



 
 
 
 
 

 
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     NH, Black 1.46 (1.00, 2.13) 0.05 

     NH, Other 1.40 (0.85, 2.31) 0.18 

OR, odds ratio; aOR, adjusted odds ratio; NH, Non-Hispanic 

† Cases with unknown stage and unknown covariates were excluded.  

§ Includes Asian, American Indian, Alaska Native, and Pacific Islander  

♦Other insurance includes Indian/Public Health Service, Military, TRICARE, Veterans Affairs, and insurance not otherwise specified. 

Anogenital Cancer Survival and Mortality 

Figure 2 represents the adjusted cumulative survival of HPV-associated AG cancers. NH Black males had 
lower cumulative (Fig. 2) and mean survival times (Table 3) relative to the other racial/ethnic groups for both 
penile and anorectal cancers. Conversely, NH Other males had higher cumulative (Fig. 2) and mean survival 
(Table 3) of penile cancers relative to the other racial/ethnic groups. 

Figure 2: Cumulative Survival of HPV-Associated Anogenital Cancers among Males, 2005-2011 (N= 11,432)* 

 



 
 
 
 
 

 
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*Mantel-Cox log rank tests for cumulative survival were statistically significant at p<0.01. 

Table 3. Mean Survival of Males with HPV-Associated Anogenital Cancers by Race/Ethnicity, United States, 
2005-2011 (N=11,258)* 

 Overall 
Mean months 

(95% CI) 

Hispanic 
Mean months 

(95% CI) 

NH White 
Mean months 

(95% CI) 

NH Black 
Mean months 

(95% CI) 

NH Other§ 

Mean months 
(95% CI) 

Penile 102.94 
(101.60-104.27) 

105.62 
(102.42-108.82) 

102.91 
(101.31-104.50) 

95.68 
(91.11-100.26) 

112.05 
(105.60-118.50) 

Anorectal 98.10 
(97.03-99.17) 

100.81 
(96.69-104.92) 

99.28 
(98.08-100.47) 

90.64 
(87.65-93.63) 

95.53 
(86.25-104.81) 

HPV, human papillomavirus; NH, Non-Hispanic  

*Unadjusted; All log rank Mantel-Cox tests were statistically significant at p<0.01 

§ Includes Asian, American Indian, Alaska Native, and Pacific Islander 

 
Table 4 describes the predictors of AG cancer-
specific mortality stratified by anatomic site. In 
multivariable analyses adjusting for all covariates 
except treatment (Model 1), independent predictors 
of higher penile cancer-specific mortality included: 
NH Black race, Medicaid or Medicare, regional or 
distant stage diagnosis, and residence in high 
poverty (20%) areas. Penile cancer-specific 
mortality was significantly lower in males living in 

the geographic South and Midwest compared to 
the Northeast. After adjusting for treatment, there 
was an attenuation of mortality for stage at 
diagnosis (Model 2). Higher mortality was observed 
for all treatment groups compared to surgery 
alone, with individuals receiving no treatment 
experiencing more than 3.5 times higher cancer-
specific mortality (aHR 3.54, 95% CI 2.61-4.80).  



 
 
 
 
 

 
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Among males with anorectal cancers, after 
adjusting for all covariates except treatment (Model 
3), independent predictors of higher cancer-specific 
mortality included: NH Black race; all insurances 
compared to private; regional or distant stage at 
diagnosis; and residence in moderate to high 
poverty areas. Similar relationships were found after 
adjustment for treatment (Model 4) with a few 

notable exceptions. We found that residence in the 
Western/Pacific region became significantly higher 
than the Northeast and a sizable attenuation of 
hazards for regional and distant stage. Men who 
received no treatment experienced more than 4.5 
times higher cancer-specific mortality (aHR 4.53, 
95% CI 3.57,-5.74). 

Table 4. Predictors of Cause-Specific Mortality from HPV-Associated Anogenital Cancers among Males in the 
United States, 2005-2011 (N=11,432)† 

 Penile Cancers (n=4,383) 

 

Anorectal Cancers (n=7,049) 

 Multivariable Model 1 Multivariable Model 2 Multivariable Model 3 Multivariable Model 4 

Characteristic aHR# (95% CI) aHR## (95% CI) aHR# (95% CI) aHR## (95% CI) 

Race/Ethnicity 

NH, White 1.00  1.00  1.00  1.00  

Hispanic/Latino 0.84 (0.70, 1.02) 0.83 (0.69, 1.00) 0.95 (0.78, 1.15) 0.93 (0.76, 1.13) 

NH, Black 1.25 (1.03, 1.51)* 1.23 (1.01, 1.49)* 1.29 (1.14, 1.46)* 1.25 (1.10, 1.42)* 

NH, Other§ 0.72 (0.48, 1.09) 0.69 (0.45, 1.05) 0.97 (0.67, 1.40) 0.94 (0.65, 1.38) 

Age at diagnosis (years) 

< 54  1.00 1.00 1.00 1.00 

55-64 1.19 (0.99, 1.44) 1.21 (1.01, 1.46)* 1.04 (0.94, 1.17) 1.00 (0.90, 1.12) 

65 + 1.17 (0.95, 1.44) 1.23 (0.99, 1.53) 1.09 (0.96, 1.24) 1.00 (0.88, 1.13) 

Insurance Type 

Private 1.00 1.00 1.00 1.00 

Medicare 1.27 (1.04, 1.54)* 1.28 (1.05, 1.56)* 1.72 (1.51, 1.95)* 1.72 (1.50, 1.96)* 

Medicaid 1.34 (1.05, 1.71)* 1.28 (1.00, 1.64)* 1.67 (1.44, 1.93)* 1.67 (1.44, 1.94)* 

Other♦ 0.94 (0.74, 1.18) 0.91 (0.72, 1.15) 1.34 (1.16, 1.56)* 1.32 (1.14, 1.54)* 

No Insurance/Self Pay 1.04 (0.80, 1.35) 1.06 (0.81, 1.38) 1.27 (1.07, 1.51)* 1.21 (1.01, 1.44)* 

Stage at Diagnosis  

Local 1.00 1.00 1.00 1.00 

Regional 3.45 (3.02, 3.94)* 3.02 (2.63, 3.48)* 2.30 (2.08, 2.54)* 2.18 (1.96, 2.43)* 

Distant 18.14 (14.65, 22.46)* 11.52 (9.08, 14.61)* 7.40 (6.58, 8.33)* 6.14 (5.41, 6.96)* 

Residence  

Large Metropolitan 1.00 1.00 1.00 1.00 

Non-Metropolitan 1.02 (0.88, 1.19) 1.03 (0.88, 1.20) 0.93 (0.82, 1.05) 0.91 (0.80, 1.04) 

% Persons below Poverty at Residence 



 
 
 
 
 

 
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 < 9.9% 1.00 1.00 1.00 1.00 

 10-19.99% 1.10 (0.89, 1.35) 1.11 (0.90, 1.37) 1.26 (1.08, 1.46)* 1.24 (1.06, 1.45)* 

 > 20% 1.33 (1.04, 1.70)* 1.33 (1.04, 1.71)* 1.42 (1.18, 1.70)* 1.38 (1.14, 1.67)* 

Geographic Region 

 Northeast 1.00 1.00 1.00 1.00 

 South 0.79 (0.65, 0.97)* 0.77 (0.63, 0.95)* 1.13 (0.97, 1.32) 1.16 (0.99, 1.35) 

 Midwest 0.74 (0.59, 0.93)* 0.73 (0.58, 0.93)* 1.05 (0.88, 1.26) 1.12 (0.94, 1.35) 

 West/Pacific 0.86 (0.69, 1.08) 0.84 (0.67, 1.05) 1.14 (0.97, 1.35) 1.21 (1.02, 1.44)* 

Treatment Modality 

 Surgery Only  1.00  1.00 

 Radiation or  

 Chemotherapy Only 

 2.40 (1.72, 3.35)*  2.45 (1.99, 3.01)* 

 Surgery + Radiation  

 or Chemotherapy 

 2.15 (1.80, 2.55)*  1.27 (0.97, 1.66) 

 Radiation +  

 Chemotherapy 

 1.86 (1.16, 2.96)*  1.50 (1.26, 1.79)* 

 All Modalities  2.06 (1.57, 2.71)*  1.23 (1.02, 1.49)* 

 No Treatment  3.54 (2.61, 4.80)*  4.53 (3.57, 5.74)* 

HPV, human papillomavirus; NH, Non-Hispanic; HR, hazards ratio; aHR, adjusted hazards ratio 
† Cases with unknown stage and unknown covariates were excluded.  
# Adjusted for all other variables excluding treatment modality 
##Adjusted for all other variables including treatment modality 
* p ≤0.01 
§ Includes Asian, American Indian, Alaska Native, and Pacific Islander  
♦Other insurance includes Indian/Public Health Service, Military, TRICARE, Veterans Affairs, and insurance not otherwise specified. 

 

In interaction analyses (Supplemental Table 2), 
race/ethnicity modified the relationship of penile 
cancer mortality and age, stage, residence in a 
metropolitan area, and geographic region. 
Compared with NH white males of the same age 
group, NH Black males less than age 55 years had 
higher hazards of death (aHR 1.53, 95% CI 1.09-
2.14). Relative to NH White males diagnosed at the 
same stage, lower cancer-specific mortality was 
observed in NH Other (aHR 0.35, 95% CI 0.14-0.84) 
and Hispanic males (aHR 0.45, 95% CI 0.21-0.97) 

with local and distant stage penile cancers, 
respectively. Lower cancer-specific mortality was 
also observed in NH Black males living in the 
Midwest (aOR 0.36, 95% CI 0.14-0.90) and Hispanic 
males living in the Northeast (aOR 0.37, 95% CI 
0.20-0.67) compared to NH White males living in 
those regions. For anorectal cancer mortality, there 
were no significant interactions between 
race/ethnicity and other variables. 

 

 



 
 
 
 
 

 
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Supplemental Table 2: Interactions of Race/Ethnicity with Covariates, Cancer-Specific Mortality from HPV-
Associated Penile Cancers among Males in the United States, 2005-2011 (N=4,383)† 

 Penile Cancer-Specific Mortality 

Characteristic aHR (95% CI) p-value 

Age at diagnosis (years)  0.44 

 < 54    

     NH, White 1.00  

     Hispanic/Latino 1.06 (0.79, 1.43) 0.70 

     NH, Black 1.53 (1.09, 2.14) 0.01 

     NH, Other§ 0.75 (0.33, 1.69) 0.48 

 55-64   

     NH, White 1.00  

     Hispanic/Latino 0.87 (0.53, 1.43) 0.58 

     NH, Black 0.67 (0.39, 1.14) 0.14 

     NH, Other 0.50 (0.09, 2.77) 0.43 

 65 +   

     NH, White 1.00  

     Hispanic/Latino 1.01 (0.56, 1.78) 0.99 

     NH, Black 1.25 (0.69, 2.25) 0.46 

     NH, Other 1.44 (0.17, 12.00) 0.73 

Insurance Type  0.31 

 Private   

     NH, White 1.00  

     Hispanic/Latino 0.79 (0.54, 1.16) 0.23 

     NH, Black 1.16 (0.74, 1.81) 0.52 

     NH, Other 0.70 (0.31, 1.59) 0.40 

 Medicare   

     NH, White 1.00  

     Hispanic/Latino 1.11 (0.61, 2.04) 0.73 

     NH, Black 0.76 (0.39, 1.47) 0.42 

     NH, Other 0.53 (0.06, 5.08) 0.58 

 Medicaid   

     NH, White 1.00  

     Hispanic/Latino 1.04 (0.55, 1.96) 0.91 

     NH, Black 0.94 (0.45, 1.95) 0.87 



 
 
 
 
 

 
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     NH, Other 0.24 (0.04, 1.39) 0.11 

 Other¶   

     NH, White 1.00  

     Hispanic/Latino 1.98 (0.98, 3.98) 0.06 

     NH, Black 1.78 (0.88, 3.60) 0.11 

     NH, Other 0.37 (0.02, 5.75) 0.48 

 No Insurance/Self Pay   

     NH, White 1.00  

     Hispanic/Latino 1.48 (0.75, 2.91) 0.26 

     NH, Black 1.51 (0.71, 3.20) 0.28 

     NH, Other ----- ----- 

Stage at Diagnosis   0.01 

 Local   

     NH, White 1.00  

     Hispanic/Latino 0.81 (0.60, 1.07) 0.14 

     NH, Black 1.20 (0.88, 1.62) 0.24 

     NH, Other 0.35 (0.14, 0.84) 0.02 

 Regional   

     NH, White 1.00  

     Hispanic/Latino 0.79 (0.52, 1.19) 0.26 

     NH, Black 1.06 (0.68, 1.65) 0.79 

     NH, Other 2.21 (0.58, 8.41) 0.24 

 Distant   

     NH, White 1.00  

     Hispanic/Latino 0.45 (0.21, 0.97) 0.04 

     NH, Black 0.80 (0.37, 1.70) 0.56 

     NH, Other ----- ----- 

Residence   0.41 

 Large Metropolitan   

     NH, White 1.00  

     Hispanic/Latino 0.86 (0.73, 1.02) 0.09 

     NH, Black 1.31 (1.09, 1.57) 0.01 

     NH, Other 0.63 (0.42, 0.96) 0.03 

 Non-Metropolitan   

     NH, White 1.00  

     Hispanic/Latino 1.56 (0.87, 2.80) 0.14 



 
 
 
 
 

 
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     NH, Black 1.27 (0.75, 2.14) 0.38 

     NH, Other 0.85 (0.22, 3.32) 0.82 

% Persons below Poverty at Residence  0.14 

 < 9.9%   

     NH, White 1.00  

     Hispanic/Latino 0.24 (0.09, 0.64) 0.01 

     NH, Black 1.01 (0.53, 1.93) 0.97 

     NH, Other 0.35 (0.09, 1.40) 0.14 

 10-19.99%   

     NH, White 1.00  

     Hispanic/Latino 3.50 (1.06, 11.62) 0.04 

     NH, Black 1.72 (0.74, 4.01) 0.21 

     NH, Other 0.63 (0.11, 3.60) 0.60 

 > 20%   

     NH, White 1.00  

     Hispanic/Latino 3.71 (1.06, 13.03) 0.04 

     NH, Black 1.45 (0.58, 3.61) 0.42 

     NH, Other 2.43 (0.40, 14.92) 0.34 

Geographic Region  0.01 

 Northeast   

     NH, White 1.00  

     Hispanic/Latino 0.37 (0.20, 0.67) 0.01 

     NH, Black 0.91 (0.49, 1.69) 0.76 

     NH, Other 0.45 (0.14, 1.43) 0.18 

 South   

     NH, White 1.00  

     Hispanic/Latino 0.70 (0.33, 1.45) 0.34 

     NH, Black 0.49 (0.23, 1.04) 0.06 

     NH, Other 0.59 (0.07, 5.10) 0.63 

 Midwest   

     NH, White 1.00  

     Hispanic/Latino 0.44 (0.13, 1.47) 0.18 

     NH, Black 0.36 (0.14, 0.90) 0.03 

     NH, Other 3.27 (0.36, 30.07) 0.29 

 West/Pacific   

     NH, White 1.00  



 
 
 
 
 

 
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     Hispanic/Latino 1.26 (0.61, 2.59) 0.53 

     NH, Black 0.46 (0.17, 1.22) 0.12 

     NH, Other 0.55 (0.09, 3.54) 0.53 

Treatment Modality  0.54 

 Surgery Only   

     NH, White 1.00  

     Hispanic/Latino 0.82 (0.67, 1.00) 0.05 

     NH, Black 1.22 (0.98, 1.51) 0.07 

     NH, Other 0.58 (0.35, 0.97) 0.04 

 Radiation or Chemotherapy Only   

     NH, White 1.00  

     Hispanic/Latino 1.74 (0.61, 4.91) 0.30 

     NH, Black 2.21 (0.93, 5.23) 0.07 

     NH, Other ----- ----- 

 Surgery + (Radiation or Chemotherapy)   

     NH, White 1.00  

     Hispanic/Latino 1.47 (0.91, 2.34) 0.11 

     NH, Black 0.76 (0.44, 1.30) 0.32 

     NH, Other 0.51 (0.12, 2.26) 0.38 

 Radiation + Chemotherapy   

     NH, White 1.00  

     Hispanic/Latino ----- ----- 

     NH, Black ----- ----- 

     NH, Other ----- ----- 

 All Modalities   

     NH, White 1.00  

     Hispanic/Latino 1.18 (0.56, 2.49) 0.65 

     NH, Black 1.17 (0.46, 3.00) 0.74 

     NH, Other ----- ----- 

 No Treatment   

     NH, White 1.00  

     Hispanic/Latino 0.82 (0.67, 1.00) 0.05 

     NH, Black 1.04 (0.47, 2.30) 0.92 

     NH, Other ----- ----- 

HR, hazards ratio; aHR, adjusted hazards ratio; NH, Non-Hispanic 

† Cases with unknown stage and unknown covariates were excluded.  



 
 
 
 
 

 
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§ Includes Asian, American Indian, Alaska Native, and Pacific Islander.  

♦Other insurance includes Indian/Public Health Service, Military, TRICARE, Veterans Affairs, and insurance not otherwise specified. 

---- suppressed for unreliable estimates due to case counts below 6. 
 
DISCUSSION 
To our best knowledge, the present study is the 
most comprehensive examination of HPV-
associated AG cancer health outcomes among 
males living across the United States. Prior studies 
have focused on one particular outcome or did not 
include covariates such as insurance status or 
geographic region in their analyses (Huang et al., 
2020; Osazuwa-Peters et al., 2021; Slopnick et al., 
2016). This study contributes to the literature of 
HPV-associated AG cancers in specifically analyzing 
the disparities in incidence, late-stage, survival, and 
mortality among males of multiple racial/ethnic 
groups.  

Previous incidence estimates of HPV-associated AG 
cancers in the United States have been based on 
study populations consisting primarily of NH White 
and NH Black men due to sample size 
considerations and the relative rarity of penile and 
anal cancer compared to other cancer types (Arora 
et al., 2017; Baughman and Shah, 2016; Bian et al., 
2021; Centers for Disease Control and Prevention, 
2020). Similar to other studies, NH White males 
represented the largest proportion of our study 
sample, regardless of anatomic site or stage (Huang 
et al., 2020; Osazuwa-Peters et al., 2021), while NH 
Black males had the highest incidence and mortality 
of anorectal cancers (Arora et al., 2017; Deshmukh 
et al., 2020; Goksu et al., 2020). Additionally, we 
found Hispanic males had the highest age-adjusted 
incidence rate of penile cancers regardless of 
disease stage, and NH Black males had later stage 
at diagnosis, lower survival, and higher mortality for 
both penile and anorectal cancers. Furthermore, 
certain subgroups of Hispanic and NH Other males 
were found to have higher late stage diagnosis of 

penile (Hispanics living in South and West/Pacific) 
and anorectal cancer (NH Other males 65 years and 
older). Inclusion of Hispanic and NH Other males 
(Asian, Pacific Islander, Native American, Alaskan 
Native) and controlling for potential confounders 
contribute uniquely to the literature about male 
HPV-associated AG cancers, which can lead to 
more targeted interventions to reduce the 
incidence, later stage at diagnosis, and mortality in 
men of color. 

The lower survival and higher mortality rates among 
NH Black males for both penile and anorectal 
cancers may be associated with delayed treatment 
initiation, later stage at diagnosis, lower rates of 
radiation therapy, and SES disparities (Ahmad et al., 
2019; Attalla et al., 2018; Baughman and Shah, 2016; 
Fields et al., 2019; Goksu et al., 2020; Gupta et al., 
2017). However, our observed disparity in mortality 
persisted after controlling for stage, treatment, and 
markers of SES. A potential contributing factor may 
be HIV co-infection with HPV. Studies have noted 
disporportionately higher rates of contracting HIV 
among NH Black men, especially men who have sex 
with men (MSM) relative to white men, and there 
has been a rise in the HIV-infection of NH Black 
males over the last three decades (Heckman et al., 
1999; Leeds and Fang, 2016; Millett et al., 2007). HIV 
is a known risk factor for anal cancer, and the co-
infection of HIV and HPV represents a significant 
challenge to a progressively diminished immune 
system (Burd, 2003). Additional clinician-related 
challenges include a lack of formal 
recommendations for use of anal Pap tests, relative 
infrequency of anal cancer cases, and lack of 
familiarity with the procedure and purpose of anal 
Pap testing (Liszewski et al., 2014). Studies 
examining the potential cost-effectiveness of anal 



 
 
 
 
 

 
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cytology screening have found that screening MSM 
every 2–3 years would be cost-effective and have 
life-expectancy benefits, and that screening could 
be easily incorporated into a primary care practice 
(Goldie et al., 2000; Siddharthan et al., 2019). NH 
Black MSM are 80% less likely to report anal cancer 
screening relative to their NH White counterparts, 
and thus, less likely to benefit from early detection 
of anal cancer (Hicks et al., 2019), potentially leading 
to later stage at diagnosis and higher mortality.  

Though penile cancer incidence is rare, it can cause 
significant psychological distress, especially related 
to a man’s self-esteem and sexual function (Harju et 
al., 2021). Our study findings showing Hispanic 
males having the highest age-adjusted incidence 
rates of penile cancer is consistent with previous 
studies (Huang et al., 2020; Ortiz et al., 2018). We 
also found Hispanic males to be diagnosed at later 
stages compared with NH White males, particularly 
among Hispanic males living in the South and 
West/Pacific regions of the U.S. Researchers 
partially attribute this to the lower rates of 
circumcision among Hispanic males (Colón-López 
et al., 2010), and lack of circumcision may be more 
prevalent among recent Hispanic immigrants who 
predominantly reside in the South and Western U.S. 
(Passel et al., 2022). Circumcision potentially has a 
protective mechanism by decreasing the likelihood 
of phimosis and by removing the foreskin as a site 
susceptible to the development of penile cancer 
(Larke et al., 2011). This may be why Hispanic males 
with HIV have higher penile cancer rates but lower 
anal cancer rates compared with NH White and 
Black males with HIV (Cruz et al., 2019; Ortiz et al., 
2018).  

No differences in mortality were observed between 
Hispanic and NH White males for either AG cancer. 
However, interaction analyses revealed lower 
cancer-specific mortality in Hispanic males with 
distant disease and those living in the Northeasten 

region of the country relative to NH White males of 
the same disease stage and region, respectively. 
This trend recurs throughout cancer research and 
other disease studies and has led to the emergence 
of a "Hispanic Paradox" or "Healthy Migrant Effect," 
which suggest that migration demands exerted a 
selective effect that leads to better health and 
mortality outcomes compared to NH White and NH 
Black males in similarly disadvantaged conditions 
(Thomson et al., 2013). However, extreme caution 
should be used when considering this hypothesis 
during health intervention planning because of the 
serious impact on health policy and likelihood of 
negatively impacting healthcare delivery to 
Hispanic populations that may still be at risk, 
including MSM and HIV-positive Hispanic males.  

NH Other males were observed to have the lowest 
age-adjusted incidence of penile and anorectal 
cancer among all groups. The population that 
compose NH Other are under-studied, therefore, it 
is unclear why they have lower incidence of HPV-
associated cancers and improved prognosis relative 
to other racial/ethnic groups. Among men, Asians 
and Pacific Islanders have the lowest incidence of 
HPV infection and lower probability of acquiring 
new HPV infections relative to other ethnic groups 
(Schabath et al., 2013). Additionally, Asians have 
been found to have lower cancer-specific mortality 
of any cancer compared to NH White males in all 
insurance status categories (Benard et al., 2008; Pan 
et al., 2017). Our study reveals additional health 
outcomes among NH Other males with HPV-
associated AG cancers, particularly in certain 
subgroups. For example, NH Other males were 
found to have similar odds of late-stage diagnosis 
and risks of mortality from penile cancers relative to 
NH White males. However, those diagnosed at local 
stage had 0.35 times lower hazards of death 
compared to NH White males diagnosed at local 
stage. Conversely, NH Other males with anorectal 
cancer had 29% higher odds of late-stage diagnosis 



 
 
 
 
 

 
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RESEARCH 

relative to NH White males; specifically, those older 
than 65 years of age had three times higher odds 
of late-stage diagnosis relative to NH White males 
of the same age group. Future studies are 
necessary in understanding why certain subgroups 
of NH Other males experience better outcomes in 
penile cancer, while other subgroups have worse 
outcomes for anorectal cancer.  

Limitations 
Though our study included several established 
variables contributing to stage at diagnosis and 
overall survival in male AG cancers across 
racial/ethnic groups, the NAACCR database does 
not contain other information, such as sociocultural 
and behavioral factors as well as comorbidities that 
may impact our results. Known risk factors for anal 
and penile cancer include anal intercourse, lack of 
circumcision, immunosuppression, HIV-infection, 
and solid-organ transplantation (Amirian et al., 
2013; Clifford et al., 2020; van der Zee et al., 2013). 
These factors may be differentially distributed 
across racial/ethnic groups and within subgroups of 
MSM and those engaging in higher-risk sexual 
behaviors (Amirian et al., 2013). Additionally, HPV 
status was not molecularly determined but based 
on supposition that cancers at particular sites and 
histologies are associated with HPV (Centers for 
Disease Control and Prevention, 2020), which may 
have led to misclassification of cases and an 
overestimate of the number of AG squamous cell 
carcinomas in our cohort. Furthermore, a limitation 
of the NAACCR database is a lack of information on 
the immigration status or birthplace of individuals 
identified as Hispanic or Asian. Since intragroup 
variability may be substantial among Hispanics 
(Martinez Tyson et al., 2018) and Asians (Thompson 
et al., 2016), future studies are needed to 
disentangle and understand AG outcomes among 
different Hispanic ethnicities and Asian subgroups. 

CONCLUSION 
This study highlights different racial/ethnic 
disparities in health outcomes among males 
depending on site of HPV-associated AG cancer. 
When considering the strong association between 
HPV and anal (>90%) and penile cancer (64%), as 
well as the potential reduction of cancer risk with 
HPV vaccination (Stier et al., 2016), our findings call 
for increasing HPV immunizations among all males. 
Additionally, increasing awareness of symptoms 
and signs of penile and anal cancer, as well as the 
utility of anal pap smears in high-risk populations 
may help to improve early detection, particularly in 
men of color. Finally, improving access to treatment 
is paramount for decreasing mortality in males with 
HPV-associated AG cancers, especially for Black 
men. 

Author Contributions 
SV, AMS, and JMF designed the research study. SV, 
AMS, JMF acquired and analyzed the data. All 
authors interpreted the data. SV, SS, DR drafted the 
manuscript. AMS and JMF revised the manuscript 
critically for important intellectual content. All 
authors approved the final manuscript and agreed 
to be accountable for all aspects of the work.  

Ethics Approval 
This study was approved by the Institutional Review 
Boards at the North American Association of 
Central Cancer Registries (NAACCR) and Rutgers, 
the State University of New Jersey (Pro2019001220). 

Funding 
No funding was received for this research. 

Conflict of Interest 
AMS received travel expenses while serving as 
President and Representative-at-Large of the Board 
of Directors for the North American Association of 
Central Cancer Registries (NAACCR) and the 



 
 
 
 
 

 
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RESEARCH 

NAACCR Communications Steering Committee. 
The other authors have no conflicts of interests to 
declare. 

Acknowledgement 
The data underlying this article were provided by 
The North American Association of Central Cancer 
Registries, which granted access to the Cancer in 
North America Deluxe file.  

We thank Anna Petrova, MD, PhD, MPH and 
Ambarina Faiz, MD, PhD for their feedback on the 
analysis as part of Seiichi Villalona’s Distinction in 
Research Program at Rutgers Robert Wood 
Johnson Medical School. 

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	INTRODUCTION
	MATERIALS AND METHODS
	Data and Sample
	Stage at Diagnosis
	Survival and Mortality
	Covariates
	Statistical Analysis

	RESULTS
	Stage at Anogenital Cancer Diagnosis

	DISCUSSION
	Limitations

	CONCLUSION
	Author Contributions
	Ethics Approval
	Funding
	Conflict of Interest
	Acknowledgement

