Male Circumcision and Prevalence of Genital Human Papillomavirus Infection in Men

Table 1.  Socio-demographic characteristics of study participants by circumcision status N = 3969

	Circumcision				P-value
	No		Yes
	N = 2545 (64.1%)		N = 1424 (35.9%)
	N	%	N	%
Age					< 0.001
Mean (SD)	33.4 (10.3)		30.9 (12.1)
18–30	1115	43.8	822	57.7
31–44	1119	44.0	406	28.5
45–70	311	12.2	196	13.8
Country of residence					< 0.001
US	241	9.5	1027	72.1
Brazil	1190	46.8	197	13.8
Mexico	1114	43.8	200	14.0
Race					< 0.001
White	877	35.1	889	63.1
Black	397	15.9	218	15.5
Asian/Pacific Islander	65	2.6	46	3.3
Mexican	1020	40.8	183	13.0
Other (American Indian, Mixed)	141	5.6	73	5.2
Unknown	45		15
Marital status					< 0.001
Single	946	37.3	838	58.9
Married	1035	40.8	322	12.7
Cohabiting	373	14.7	104	4.1
Divorced/Separated/Widowed	183	7.2	158	11.1
Unknown	8		2
Education					< 0.001
<12 Years	750	29.6	133	9.3
Completed 12 Years	774	30.6	292	20.5
13–15 Years	377	14.9	623	43.8
Completed 16 Years	497	19.6	273	19.2
≥17 Years	135	5.3	102	7.2
Unknown	12		1
Current smoker					0.054
No	1916	75.4	1112	78.2
Yes	624	24.6	310	21.8
Unknown	5		2
Sexual orientation					< 0.001
MSW	2092	82.5	1245	87.7
MSWM	161	6.4	54	3.8
MSM	132	5.2	41	2.9
No sex	150	5.9	79	5.6
Unknown	10		5
Lifetime female sexual partners					0.059
Median (SD)	6 (2055.1)		7 (79.4)
0–1	440	18.5	253	18.4
2–9	1040	43.8	560	40.8
10–19	416	17.5	234	17.0
20–49	354	14.9	229	16.7
50+	124	5.2	98	7.1
Unknown	171		50
Female sexual partners in past 3–6 months					< 0.001
Mean (SD)	1.4 (2.4)		1.4 (1.7)
0	717	30.7	329	24.3
1	940	40.3	668	49.3
2	349	15.0	163	12.0
3+	326	14.0	196	14.5
Unknown	213		68
Male anal sexual partners in past 3 months					0.002
Mean (SD)	0.3 (3.3)		0.1 (1.0)
0	2341	92.9	1363	95.7
1	75	3.0	25	1.8
2	31	1.2	16	1.1
3+	73	2.9	20	1.4
Unknown	25		0
Diagnosis of STIs, ever					< 0.001
No	1992	81.3	1209	86.9
Yes	459	18.7	183	13.1
Unknown	94		32
HPV status					< 0.001
Negative	840	33.0	481	33.8
Oncogenic HPV	763	30.0	419	29.4
Non-oncogenic HPV	618	24.3	280	19.7
Unclassified HPV	324	12.7	244	17.1
HPV multiple infections					0.169
2+ HPV types	794	57.5	379	54.2
1 HPV type	587	42.5	320	45.8
Negative	840		481

NOTE. SD, standard deviation; US, the United States; MSW, men who have sex with women; MSWM, men who have sex with women and men; MSM, men who have sex with men; STI, sexually transmitted infections. Numbers in bold correspond to P values < 0.05.

Table 2.  Association between male circumcision and genital HPV detection in men

	Any HPV (n = 3969)		Oncogenic HPV (n = 2503)		Non-Oncogenic HPV (n = 2219)		Unclassified HPV (n = 1889)
	Univariate	Multivariable1	Univariate	Multivariable1	Univariate	Multivariable1	Univariate	Multivariable1
	PR (95% CI)	PR (95% CI)	PR (95% CI)	PR (95% CI)	PR (95% CI)	PR (95% CI)	PR (95% CI)	PR (95% CI)
Circumcision
No	1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0
Yes	0.99 (0.94 - 1.04)	0.96 (0.91 - 1.01)	0.98 (0.90 - 1.07)	0.95 (0.87 - 1.03)	0.87 (0.78 - 0.97)	0.85 (0.76 - 0.95)	1.21 (1.05 – 1.39)	1.07 (0.92 – 1.24)

NOTE. PR, prevalence ratio; CI, confidence interval. Numbers in bold correspond to statistically significant point estimates.
¹Adjusted for race, marital status, lifetime female sexual partners, female sexual partners in past 3–6 months and male anal sexual partners in the past 3 months.

Table 3.  Association between MC and genital HPV detection in men by lifetime number of female partners

		Circumcision
	N	No	Yes
			Univariate	Multivariable 1
			PR (95% CI)	PR (95% CI)
Any HPV
Lifetime number of female partners				P = 0.1462
1–4	1099	1.00	0.97 (0.87–1.08)	0.92 (0.81–1.03)
5–12	1183	1.00	0.98 (0.91–1.07)	0.96 (0.88–1.05)
13+	1083	1.00	1.03 (0.97–1.10)	1.03 (0.96–1.10)
Oncogenic HPV
Lifetime number of female partners				P = 0.2042
1–4	667	1.00	0.93 (0.73 - 1.19)	0.96 (0.73 - 1.26)
5–12	726	1.00	0.96 (0.82 - 1.12)	0.92 (0.77 - 1.09)
13+	697	1.00	1.06 (0.95 - 1.18)	1.06 (0.95 - 1.19)
Non-Oncogenic HPV
Lifetime number of female partners				P = 0.006 2
1–4	647	1.00	0.62 (0.45 - 0.83)	0.59 (0.42 - 0.83)
5–12	668	1.00	0.89 (0.74 - 1.07)	0.88 (0.72 - 1.08)
13+	542	1.00	1.03 (0.88 - 1.20)	1.03 (0.88 - 1.21)
Unclassified HPV
Lifetime number of female partners				P = 0.9522
1–4	717	1.00	1.24 (1.01 – 1.51)	1.03 (0.82 – 1.28)3
5–12	527	1.00	1.25 (0.96 – 1.61)	1.15 (0.86 – 1.53)3
13+	330	1.00	1.19 (0.83 – 1.71)	1.10 (0.74 – 1.62)3

NOTE. PR, prevalence ratio; CI, confidence interval. Numbers in bold correspond to statistically significant point estimates.
¹Adjusted for race, marital status, female sexual partners in past 3–6 months and male anal sexual partners in the past 3 months.
²Test for interaction between MC and lifetime number of female partners.
³Adjusted for race, marital status, and male anal sexual partners in the past 3 months.

Table 4.  Genital type-specific HPV distribution in men by circumcision status

HPV	Circumcision				N total	PR (95% CI)
	No		Yes
	N	%	N	%
Oncogenic
16	190	7.5	117	8.2	307	1.10 (0.88–1.37)
18	51	2.0	40	2.8	91	1.40 (0.93–2.11)
31	51	2.0	20	1.4	71	0.70 (0.42–1.17)
33	20	0.8	4	0.3	24	0.36 (0.12–1.04)
35	41	1.6	24	1.7	65	1.05 (0.63–1.72)
39	96	3.8	49	3.4	145	0.91 (0.65–1.28)
45	47	1.8	18	1.3	65	0.68 (0.40–1.17)
51	158	6.2	95	6.7	253	1.07 (0.84–1.37)
52	166	6.5	78	5.5	244	0.84 (0.65–1.09)
56	55	2.2	20	1.4	75	0.65 (0.39–1.08)
58	71	2.8	27	1.9	98	0.68 (0.44–1.05)
59	131	5.1	91	6.4	222	1.24 (0.96–1.61)
68	54	2.1	37	2.6	91	1.22 (0.81–1.85)
Non-oncogenic
6	156	6.1	84	5.9	240	0.96 (0.74–1.24)
11	43	1.7	11	0.8	54	0.46 (0.24–0.88)
26	4	0.2	4	0.3	8	1.79 (0.45–7.14)
40	54	2.1	9	0.6	63	0.30 (0.15–0.60)
42	40	1.6	15	1.1	55	0.67 (0.37–1.21)
53	141	5.5	86	6.0	227	1.09 (0.84–1.41)
54	56	2.2	34	2.4	90	1.09 (0.71–1.65)
55	64	2.5	35	2.5	99	0.98 (0.65–1.47)
61	147	5.8	39	2.7	186	0.47 (0.34–0.67)
62	218	8.6	102	7.2	320	0.84 (0.67–1.05)
64	3	0.1	1	0.1	4	0.60 (0.06–5.72)
66	124	4.9	81	5.7	205	1.17 (0.89–1.53)
67	16	0.6	4	0.3	20	0.45 (0.15–1.33)
69	7	0.3	1	0.1	8	0.26 (0.03–2.07)
70	71	2.8	29	2.0	100	0.73 (0.48–1.12)
71	53	2.1	5	0.4	58	0.17 (0.07–0.42)
72	39	1.5	12	0.8	51	0.55 (0.29–1.05)
73	51	2.0	22	1.5	73	0.77 (0.47–1.27)
81	94	3.7	28	2.0	122	0.53 (0.35–0.81)
82	18	0.7	12	0.8	30	1.19 (0.58–2.47)
83	81	3.2	31	2.2	112	0.68 (0.45–1.03)
84	197	7.7	119	8.4	316	1.08 (0.87–1.34)
IS39	20	0.8	6	0.4	26	0.54 (0.22–1.33)
CP6108	162	6.4	113	7.9	275	1.25 (0.99–1.57)

NOTE. PR, prevalence ratio; CI, confidence interval. Numbers in bold correspond to statistically significant point estimates.

Authors and Disclosures

Ginesa Albero^1,2,3, Luisa L Villa⁴, Eduardo Lazcano-Ponce⁵, William Fulp⁶, Mary R Papenfuss⁶, Alan G Nyitray⁶, Beibei Lu⁶, Xavier Castellsagué^1,2, Martha Abrahamsen⁶, Danélle Smith⁶, F Xavier Bosch¹, Jorge Salmerón⁷, Manuel Quiterio⁵ and Anna R Giuliano<sup>6*

1</sup> Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Program (CERP), Catalan Institute of Oncology (ICO), L'Hospitalet de Llobregat 08908, Barcelona, Spain
² CIBER en Epidemiología y Salud Pública – CIBERESP (Epidemiology and Public Health Biomedical Research Consortium), Barcelona, Spain
³ Program in Public Health and the Methodology of Biomedical Research, Universitat Autonoma de Barcelona (UAB). Campus Universitat Autonoma, s/n, Cerdanyola del Valles, 08193, Barcelona, Spain
⁴ Ludwig Institute for Cancer Research, São Paulo, 01323–903, Brazil
⁵ Instituto Nacional de Salud Publica, Cuernavaca, 62100, Mexico
⁶ H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA
⁷ Instituto Mexicano del Seguro Social, Cuernavaca, 62140, Mexico

Competing interests
G.A. My research unit is involved in vaccine trials organized by GlaxoSmithKline and Merck/Sanofi Pasteur MSD. Travel fund to conferences/symposia/meetings are occasionally granted by either GlaxoSmithKline, Sanofi Pasteur MSD or Qiagen. A.R.G. and L.L.V. are on the speakers' bureau for Merck and are members of its advisory board. A.G.N. has received research funding from Merck & Co. X.C. Research Grants (GlaxoSmithKline, Merck Sharp & Dohme, Sanofi Pasteur MSD); Speakers Bureau (GlaxoSmithKline, Sanofi Pasteur MSD); Steering Committee (GlaxoSmithKline, Sanofi Pasteur MSD). F.X.B. Advisory Board (GlaxoSmithKline, Merck Sharp & Dohme, Sanofi Pasteur MSD); Speakers Bureau (GlaxoSmithKline); Research Grants (Merck Sharp & Dohme, Sanofi Pasteur MSD). X.C. and F.X.B. My research unit is involved in vaccine trials organized by GlaxoSmithKline and Merck/Sanofi Pasteur MSD. Travel fund to conferences/symposia/meetings and honorarium are occasionally granted by either GlaxoSmithKline, Merck, Sanofi Pasteur MSD, MTM or Qiagen. All other authors declare that they have no competing interests.

*Corresponding author
anna.giuliano@moffitt.org