Human Papillomavirus Seroprevalence Among Men Entering Military Service and Seroincidence After Ten Years of Service

Abstract

Vaccination against human papillomavirus (HPV) is recommended to prevent cervical cancer among women, but the benefits of HPV vaccination for males are less obvious. This study characterized HPV acquisition among male military members by evaluating both seroprevalence at entry into service and seroincidence of HPV infection after ten years of service. At entry, 29 of 200 (14.6%) male service members were positive for HPV serotypes 6, 11, 16, or 18. Of 199 initially seronegative for at least one of the four HPV serotypes, 68 (34.2%) seroconverted to one or more serotypes at ten years; more than one-third of these were seropostive for oncogenic HPV serotypes. This estimate of HPV seroprevalence among male military accessions is higher than that reported among U.S. civilian males. Vaccination to prevent genital warts and cancers resulting from HPV infection may decrease health care system burdens. Further analyses are warranted to understand the potential costs and benefits of a policy to vaccinate male service members.

Background

Human papillomavirus (HPV) is responsible for more health care visits among active duty service members than gonorrhea (GC) and chlamydia (CT) combined.¹ An effective vaccine to prevent infection with vaccine serotypes is available, although administration of the three-dose series is expensive.² Infection with the oncogenic HPV serotypes 16 and 18 can cause long-term morbidity or mortality due to cervical and vulvo-vaginal cancer among women, penile cancer among men, and anal and oropharyngeal cancers in both genders. HPV may also play a role in esophageal and lung cancer.³ Annual numbers of HPV-associated cancers are estimated at 25,000 and 550,000 cases in the U.S. and worldwide, respectively.³ Based on demonstrated efficacy and evidence of cost effectiveness, HPV vaccine is currently approved for the prevention of cervical cancer.² Recently the U.S. Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recognized the potential benefits of immunizing young men and recommended vaccination for both males and females.² The U.S. military’s implementation of this recommendation has been slow, as evidenced by low initiation and completion rates among servicewomen.^4,5 Assessment of HPV infection rates among male service members is important to evaluate the potential benefits of vaccination.

As obtaining genital HPV DNA samples from large populations is difficult, HPV serology is increasingly used to characterize the epidemiology of HPV infection^6–8, despite evidence of incomplete seroconversion and possible antibody decline^9,10. In one study, seropositivity was observed in approximately 60 percent of women with newly detected cervical HPV DNA.¹¹ The correlation between HPV seroprevalence and cervical DNA positivity is reportedly high (r=0.81).¹² Several assays are available including a multiplex Luminex® assay that quantitates neutralizing antibodies to HPV serotypes 6, 11, 16 and 18. This assay was used in the recent U.S. National Health and Nutrition Examination Survey (NHANES) serosurvey⁸ and has been well validated.^{13, 14–16}

Population-based studies have demonstrated that HPV seroprevalence is low in late adolescence (1–8%), increases over the first decade of adulthood, and among those at risk, is high (15–35%) by age 40.^{6–8,11,12,16,17} The timeline of HPV acquisition may be accelerated in a highly sexually active population such as military personnel.^18–20 Among female service members attending a sexually transmitted infections clinic, HPV seroprevalence was reported at 45 to 51 percent.¹⁸ The present report describes an effort to characterize HPV acquisition among U.S. military males by evaluating both seroprevalence at entry into service and seroincidence of HPV infection after ten years of service.

Methods

The study population consisted of males who entered the active component of the U.S. military in 2000, were between 17 and 26 years of age at entry, and had serum samples available in the DoD Serum Repository²¹ within one year of entry into service and at 10 years (+/− 1 year) after entry into service. Qualifying individuals were stratified into the eight U.S. census regions based on the state of their home of record. A random sample of 25 individuals per region was selected for the study for a total sample size of 200 individuals. By chance alone, due to multiple selection criteria, no Air Force members were included in the study population. Serum samples from both time points were assayed for HPV serotypes 6, 11, 16, and 18 using a validated, commercially available, Luminex ® assay (PPD Vaccines & Biologics, Wayne, PA).^13–15,22 Individuals were classified as positive or negative by serotype according to published assay cutoffs.²³ Demographic and military characteristics were derived from the Defense Medical Surveillance System.²¹ The study protocol was approved by scientific and institutional review boards…

Prevalent HPV cases were defined as individuals who were seropositive for one or more HPV serotypes at accession. Incident cases were individuals who were negative for one or more HPV serotypes at the first time point and subsequently positive for a prior negative serotype approximately 10 years later. Thus, incident infection could be observed among those with a baseline (prevalent) infection at accession due to seroconversion to different serotypes.

Results

The demographic and military characteristics of the population at accession were typical of active component military members (Table 1). Overall seroprevalence for any of the four studied HPV serotypes at accession was 14.6 percent (Table 1). At entry, 20 (10.1%) service members were seropositive to serotypes 6 or 11 (genital wart group) and 9 (4.5%) were seropositive to serotypes 16 or 18 (oncogenic group; data not shown). The highest proportions of HPV seropositivity at accession were among servicemen older than 23 years and ever-married. By race, a higher proportion of white (16.1%) than black (8.8%) service members were seropositive for any serotype.

Table 1.

Demographic characteristics and HPV seropositivity at accession among a sample of 200 active component service members who began service in 2000 and served at least 10 years, U.S. Armed Forces

Demographic/military characteristics		HPV seropositivea
	No. (%)	No. (%b)
All individuals	200	29 (14.5)
Age group
17–19	107 (53.5)	14 (13.1)
20–21	39 (19.5)	2 (5.1)
22–23	35 (17.5)	6 (17.1)
24-26	19 (9.5)	7 (36.8)c
Race/ethnicity
White, non-Hispanic	137 (68.5)	22 (16.1)
Black, non-Hispanic	34 (17.0)	3 (8.8)
Other	29 (14.5)	4 (13.8)
Education
High school or less	168 (84.0)	24 (14.3)
Some college	4 (2.0)	0 (0.0)
College or more	7 (3.5)	1 (14.3)
Unknown	21 (10.5)	4 (19.1)
Marital Status
Married	14 (7.0)	5 (35.7)
Single	183 (91.5)	22 (12.0)c
Divorced/widowed	3 (1.5)	2 (66.7)
Rank
Enlisted	192 (96.0)	28 (14.6)
Officer/Warrant	8 (4.0)	1 (12.5)
Service
Army	90 (45.0)	16 (17.8)
Marine Corps	34 (17.0)	4 (11.8)
Navy	76 (38.0)	9 (11.8)

^aFor HPV serotypes 6, 11, 16, 18

^bPercent of individuals at risk

^cStatistically significant (p<0.05) in univariate analysis

Of the 199 males at risk of seroconversion to at least one of the four HPV serotypes (one lacked data due to assay failure on his specimen), 68 (34.2%) seroconverted to one or more serotypes at ten years (Table 2). Sixty-six subjects were newly positive for one or two serotypes, two for three serotypes, and none for all four. Incident infection was most commonly seen for the genital wart group (28.6%) as compared to the oncogenic group (12.6%; data not shown). Seroincidence was higher among service members of black than white or “other” race, (50.0%, 33.1% and 20.7%, respectively), and among those in the Army and Navy (34.1% and 36.1%, respectively) compared to the Marine Corps (25.8%). There were no statistically significant differences in seroincidence by educational level, marital status, or rank (data not shown).

Table 2.

Incident HPV infection among U.S. service members (N=199) after 10 years^a of military service, U.S. Armed Forces, 2010

Demographic/military characteristics	HPV seroincidence (%)b
	All HPV serotypes n=199	HPV 6/11 (warts) n=196	HPV 16/18 (oncogenic) n=199
All individuals	68 (34.2)	56 (28.6)	25 (12.6)
Age group
27–29	41 (38.7)	32 (31.1)	17 (16.0)
30–31	8 (20.5)	8 (20.5)	1 (2.6)
32–33	10 (28.6)	7 (20.0)	4 (11.4)
34–37	9 (47.4)	9 (47.4)	3 (15.8)
Race/ethnicity
White, non-Hispanic	45 (33.1)	35 (26.3)	15 (11.0)
Black, non-Hispanic	17 (50.0)	16 (47.1)	7 (20.6)
Other	6 (20.7)	5 (17.2)	3 (10.3)
Education
High school or less	49 (32.9)	41 (28.1)	16 (10.7)
Some college	5 (27.8)	4 (22.2)	3 (16.7)
College or more	9 (42.9)	7 (33.3)	4 (19.0)
Unknown	5 (45.5)	4 (36.4)	2 (18.2)
Marital Status
Married	51 (32.7)	42 (27.1)	18 (11.5)
Single	8 (36.4)	5 (23.8)	6 (27.3)
Other	9 (42.9)	9 (45.0)	1 (4.8)
Rank
Enlisted	56 (33.1)	47 (28.3)	20 (11.8)
Officer/Warrant	8 (38.1)	5 (23.8)	4 (19.0)
Other	4 (44.4)	4 (44.4)	1 (11.1)
Service
Army	30 (34.1)	25 (28.7)	12 (13.6)
Marine Corps	8 (25.8)	6 (19.4)	3 (9.7)
Navy	26 (36.1)	21 (30.0)	9 (12.5)
Unknown	4 (50.0)	4 (50.0)	1 (12.5)

^a±1 year;

^bPercent of individuals at risk

Discussion

This study found that 14.6% of males entering military service were seropositive for one or more of the four vaccine preventable HPV serotypes. This estimate of seroprevalence is higher than those previously reported among U.S. civilians; the NHANES HPV serosurvey found prevalences of 4.2 and 7.2 percent among males aged 20 to 24 and 25 to 29 years, respectively.⁸ The finding of higher seroprevalence among military accessions is consistent with reports of sexually transmitted disease rates among U.S. military members^24–27, who may be more prone to risk-taking than their civilian counterparts.

This study also found that incident infections with these four serotypes were common; more than one-third (34.2%) of male service members seroconverted to one or more vaccine serotypes. This finding offers data-based evidence of the potential benefit of a military HPV vaccination program for males. While the majority of new infections were due to genital wart group types, about one-third were due to oncogenic types. Prevention of genital warts and cancers resulting from HPV infection seems likely to decrease health care system burdens and associated long-term costs.²⁸ Individual consequences are also notable, especially for individuals suffer HPV-related malignancies. While cervical cancer risk among women has been significantly mitigated through the use of routine Papanicolau smears, screening for anal and oropharyngeal cancers associated with HPV infection remains difficult and rates of these cancers continue to rise.²⁹ Given the associated mortality and potentially debilitating morbidities of these malignancies and their treatments, prevention of infection with oncogenic HPV types offers a relevant benefit.

Black, non-Hispanic service members were approximately 50 percent more likely than their white, non-Hispanic counterparts to acquire a new infection with one or more of the four studied serotypes. This is in contrast to the prevalence at the time of accession which was nearly 50 percent lower among black than white service members. Sexual risk behavior differences between these groups including number and type of partners, use of protective measures such as condoms, and sexual partner networks may account for this finding and merit further study.

This investigation was limited by the small size of the sample in general, which included only 34 service members of black race. Another limitation was that the study population included only those individuals with at least 10 years of service, who may not be representative of all military accessions. Of note in this regard, the high prevalence of HPV at entrance to military service indicates that men entering active duty service are at a relatively high risk for sexually transmitted infections and would likely benefit from preventive interventions, including HPV vaccination at accession. Although the assay for serotype 11 was challenged by high variability in positive controls, results were qualitatively consistent with the other serotypes (comparable rates of positivity with similar titers) suggesting this variability did not affect our findings. Finally, HPV vaccination status was not available for analysis. However, since HPV vaccination was not recommended for routine use among males until 2011 (after the 2010 cutoff for this study), HPV vaccination was probably not a confounding factor in this analysis. Although the serologic method used in this study may have underestimated the true infection rate by up to 40%, more than one-third of service members demonstrated evidence of a new HPV infection and more than one-third of these were seropostive for oncogenic HPV serotypes. These findings provide strong evidence of the potential benefit of male HPV vaccination upon entry into military service. Further analyses are warranted to understand the potential costs and benefits of such a policy.