The Strong Protective Effect of Circumcision against Cancer of the Penis

Table 1

Prevalence of HPV at different anatomical sites for circumcised and uncircumcised men in various studies in different countries.

(a) Castellsagué et al. (2002) [45]: Spain, Columbia, Brazil, Thailand, Philippines; 26% were aged ≤37, 57% were 38–56, 25% were ≥57 years

Site	HPV	Circumcised	Uncircumcised
		(𝑛=370)	(𝑛=1543)	AOR (95% CI)
Glans, coronal sulcus
	Any HPV	5.5%	19.6%	0.37 (0.16–0.85)

(b) Svare et al. (2002) [54]: Copenhagen, Sweden, STI clinic

Site	HPV	Circumcised	Uncircumcised
		(𝑛=22)	(𝑛=112)	AOR (95% CI)
Glans, coronal sulcus,
Shaft, scrotum
	Any HPV	9%	21%	0.20 (0.06–0.60)

(c) Baldwin et al. (2004) [44]: Tucson, Arizona, STI clinic, 42% white (non-Hispanic), 39% Hispanic, 19% indigenous, Pacific Islander or Asian, age 18–70, 90% heterosexual, 82% single, condom users had 79% lower high-risk HPV and 42% higher low-risk HPV

Site	HPV	Circumcised	Uncircumcised
		(𝑛=232)	(𝑛=89)	AOR (95% CI)
Glans, coronal sulcus,
urethral meatus
	Any HPV	19.8%	41.1%	0.34 (0.20–0.57)
	High-risk	7.8%	18.8%	0.44 (0.22–0.90)
	Low-risk	12.1%	22.3%	0.44 (0.23–0.81)

(d) Weaver et al. (2004) [58]: Seattle, university students, aged 18–25, 81% white, 6% Asian, 3% African American, 2% Latino, 8% other, 97%  β-globin DNA-positive

Site	HPV	Circumcised	Uncircumcised
		(𝑛=233)	(𝑛=84)	OR (95% CI)
Glans	Any HPV	17%	32%	Not shown
All sites	Any HPV	31%	29%	0.95 (0.50–1.79; NS)

(e) Shin et al. (2004) [52]: South Korea, university students, 46% had ≥4 sex partners

Site	HPV	Circumcised	Uncircumcised
		(𝑛=296)	(𝑛=40)	OR (95% CI)
Coronal sulcus, meatus,
shaft, scrotum
	Any HPV	7.0%	8.9%	1.8 (0.4–8.2; NS)

(f) Lajous et al. (2005) [48]: Mexico City, soldiers, age 16–40 (av. 23), average 3 sex partners. condom use with prostitutes did not affect HPV prevalence

Site	HPV	Circumcised	Uncircumcised
		(𝑛=95)	(𝑛=830)	AOR (95% CI)
Coronal sulcus, meatus,
shaft, scrotum
	Any HPV	29.5%	44.0%	0.48 (0.30–0.77)

(g) Vaccarella et al. (2006) [57]: Mexico, 27 public vasectomy clinics in 14 states, average age 34 years, HPV was 60% less for condom users with regular partners and 90% less with sex workers, high-risk and low-risk HPV stated as similar within each of circumcised and uncircumcised

Site	HPV	Circumcised	Uncircumcised
		(𝑛=247)	(𝑛=532)	AOR (95% CI)
Glans/coronal sulcus,
Meatus, shaft, scrotum
	Any HPV	2.4%	11.7%	0.20 (0.10–0.40)

(h) Partridge et al. (2007) [51]: Seattle, university students, age 18–20, white 85%, Asian/Pacific Islander 8.3%, other 7.1%, unmarried

Site	HPV	Circumcised	Uncircumcised
		(𝑛=184)	(𝑛=56)	HR (95% CI)
Glans, shaft, scrotum	1.2/100PY	1.7/100PY	1.1 (0.6–2.0; NS)

(i) Hernandez et al. (2008) [59]: Hawaii, university population, most white, single, average age 29, 77% heterosexual, 53% had had ≥6 female sex partners, 50% used condoms, all HIV-negative

Site	HPV	Circumcised	Uncircumcised
		(𝑛=299)	(𝑛=80)	AOR (95% CI)
Glans/coronal sulcus
	Any HPV	29%	46%	0.51 (0.27–0.97)
	High-risk	16%	31%	0.40 (0.18–0.90)
	Low-risk	22%	39%	0.51 (0.25–1.08)
	Multiple	12%	39%	0.28 (0.12–0.67)
Shaft
	Any HPV	50%	60%	0.63 (0.42–1.22)
	High-risk	34%	38%	0.70 (0.32–1.52)
	Low-risk	45%	56%	0.59 (0.30–1.16)
	Multiple	30%	36%	0.57 (0.26–1.28)
Urine
	Any HPV	8%	16%	0.31 (0.08–1.16)
	High-risk	1%	3%	0.18 (0.004–7.69)
	Low-risk	7%	16%	0.28 (0.07–1.10)
	Multiple	1%	0%	—
Semen
	Any HPV	6%	5%	1.09 (0.17–7.14)
	High-risk	2%	0%	—
	Low-risk	6%	5%	0.86 (0.13–5.88)
	Multiple	1%	0%	—
Scrotum
	Any HPV	40%	40%	0.82 (0.43–25.0)
	High-risk	20%	20%	0.69 (0.33–2.38)
	Low-risk	33%	35%	0.69 (0.33–1.43)
	Multiple	14%	19%	0.53 (0.21–1.33)
External penis
	Any HPV	57%	67%	0.58 (0.30–1.14)
	High-risk	25%	23%	0.82 (0.28–2.38)
	Low-risk	30%	36%	0.61 (0.25–1.47)
	Any	20%	23%	0.52 (0.17–1.56)
Any site
	Any HPV	78%	83%	0.49 (0.19–1.28)
	High-risk	55%	58%	0.38 (0.11–1.28)
	Low-risk	61%	67%	0.42 (0.14–1.25)
	Multiple	39%	41%	0.35 (0.09–1.43)

(j) Nielson et al. (2009) [49]: Tucson and Tampa, aged 18–40, circumcised participants: white 76%, Indigenous 6%, black 1%, Asian/Pacific Islander 2%, other 4%; >6 sex partners 65%, condom use ≤ half = 56%, sex with partner with abnormal pap smear 26% for circumcised, 11% for uncircumcised

Site	HPV	Circumcised	Uncircumcised
		(𝑛=389)	(𝑛=74)	AOR (95% CI)
Glans/coronal sulcus
	Any HPV	29.8%	35.2%	0.44 (0.23–0.82)
	High-risk	13.9%	18.3%	0.47 (0.22–0.99)
	Low-risk	15.8%	16.9%	0.62 (0.29–1.29)
Shaft
	Any HPV	40.2%	40.9%	0.53 (0.28–0.99)
	High-risk	21.2%	25.4%	0.50 (0.25–1.00)
	Low-risk	19.1%	15.9%	0.85 (0.40–1.80)
Scrotum
	Any HPV	25.9%	24.3%	0.73 (0.37–1.44)
	High-risk	12.9%	12.9%	0.68 (0.29–2.06)
	Low-risk	12.9%	11.4%	0.86 (0.36–2.06)
Urethra
	Any HPV	7.8%	14.9%	0.17 (0.05–0.56)
	High-risk	3.9%	2.1%	1.24 (0.14–10.8)
	Low-risk	3.9%	12.8%	0.04 (0.01–0.23)
Semen
	Any HPV	4.2%	7.1%	0.48 (0.12–1.96)
	High-risk	3.1%	3.6%	0.41 (0.10–2.78)
	Low-risk	1.1%	3.6%	0.41 (0.03–5.07)
Any site
	Any HPV	51.2%	51.4%	0.53 (0.28–0.99)
	High-risk	28.8%	31.2%	0.56 (0.30–1.06)
	Low-risk	22.4%	20.3%	0.84 (0.43–1.67)

(k) Giuliano et al. (2009) [46]: USA (34%), Mexico (32%), Brazil (35%); age 18–70 (av. 32), 66% had >1 sex partner in past 3 months, 9% had had sex with male, condom use: always 20%, sometimes 32%. The respective OR became 0.70 (0.52–0.94), 0.70 (0.50–0.97), and 0.63 (0.42–0.93) after multivariate analysis

Site	HPV	Circumcised	Uncircumcised
		(𝑛=590)	(𝑛=398)	OR (95% CI)
Coronal sulcus, shaft, under foreskin, scrotum (all β-globin DNA-positive)
	Any HPV	54.8%	62.2%	0.97 (0.68–1.39)
	High-risk	41.8%	49.2%	0.93 (0.63–1.33)
	Low-risk	33.1%	40.4%	1.15 (0.74–1.79)

(l) Auvert et al. (2009) [43]: RCT, South Africa, Black, age 18–24, average 4 lifetime sex partners, consistent condom use 25%, 5% HIV-positive

Site	HPV	Circumcised	Uncircumcised
		(643)	(621)	PRR (95% CI)
Urethra
	High-risk	14.0%	23.2%	0.60 (0.46–0.79)
	Multiple high-risk	4.2%	9.9%	0.43 (0.28–0.66)

(m) Tobian et al. (2009) [55]: Rakai 1 RCT, Kenya; age 15–49 years; only β-globin positive samples

Site	HPV	Circumcised	Uncircumcised
		(𝑛=307)	(𝑛=302)	RR (95% CI)
Glans/coronal sulcus
	All HPV	35.6%	51.2%	0.70 (0.53–0.91)
	High-risk	18.0%	27.9%	0.65 (0.46–0.90)
	Low-risk	26.2%	39.4%	0.66 (0.49–0.91)
	Multiple	4.3%	12.2%	0.35 (0.17–0.71)

(n) Gray et al. (2010) [47]: Rakai, Uganda; RCT; age 15–24 (22%), 25–35 (51%), >35 (26%); condom use (35%), >1 sex partners 42%; HPV at enrolment (39%); data for 24 months: after circumcision

Site	HPV	Circumcised	Uncircumcised
		(𝑛=441)	(𝑛=399)	IRR (95% CI)
Glans/coronal sulcus
	Any high-risk HPV	19.7%	29.4%	0.67 (0.50–0.90)
	Single new high-risk HPV	12.9%	15.6%	0.89 (0.60–1.30)
	Multiple new high-risk HPV	6.7%	14.8%	0.45 (0.28–0.73)
	HPV16	3.6/100PYs	4.8/100PYs	0.75 (0.38–1.51)
	HPV18	1.6/100PYs	5.3/100PYs	0.30 (0.12–0.75)
	HPV31	1.6/100PYs	2.2/100PYs	0.74 (0.27–2.05)
	HPV33	0.5/100PYs	3.1/100PYs	0.17 (0.04–0.76)
	HPV35	1.9/100PYs	3.7/100PYs	0.50 (0.21–1.21)
	(Condom use)	22/100PYs	32/100PYs	0.68 (0.43–1.09)

(o) Tobian et al. (2011) [56]: Rakai, rural Uganda, RCT, age 15–49, consistent condom use 16%, HPV test at 12 months after circumcision, only β-globin DNA positive samples included, high-risk HPV significantly higher on coronal sulcus than on shaft

Site	HPV	Circumcised	Uncircumcised
		(𝑛=231)	(𝑛=228)	APR (95% CI)
Coronal sulcus
	Any high-risk HPV	21.5%	36.3%	0.57 (0.39–0.84)
	Multiple high-risk	7.4%	10.5%	0.71 (0.33–1.52)
Shaft
	Any high-risk HPV	15.5%	23.8%	0.66 (0.39–1.12)
	Multiple high-risk HPV	1.7%	3.8%	0.45 (0.09–2.27)

OR: odds ratio; AOR: adjusted odds ratio; NS: not significant; RR: risk ratio; PPR: prevalence risk ratio; HR: hazard ratio, 100PY: 100 person years.