Early infant male circumcision: Systematic review, risk-benefit analysis, and progress in policy

Table 1 Risk-benefit analysis for newborn male circumcision

A Conditions avoided and risk reduction
Condition	Decrease in risk1	Percent affected2	Study type and ref.	Quality score3
Pyelonephritis (infants)	–	0.60%	OS[24,25]	2+
With concurrent bacteremia	–	0.10%
Hypertension in early adulthood	–	0.10%
End-stage renal disease in early adult	–	0.06%
Urinary tract infections: Age 0-1 yr	90%	1.30%	Meta[22]	1+
Urinary tract infections: Age 1–16 yr	85%	2.70%	Meta[22]	1+
Urinary tract infections: Age > 16 yr	70%	28%	Meta[22]	1+
Urinary tract infections: Lifetime	72%	27%	Meta[22]	1+
Phimosis4	> 90%	10%	OS[33-45,47]	2+
Balanitis	68%	10%	Meta[54]	1+
Candidiasis (thrush)	60%	10%	OS[19]	2+
High-risk HPV infection	56%	10%	Meta[73]	1++
	53%-65%	4%	Meta[65]	1++
	40%	6-10%	RCT[61-63,70-72]	1++
HIV (acquired heterosexually)	60%	0.20%	OS[90]	2+
	70%	0.10%	Meta[87]	1++
Genital ulcer disease	50%	1%	OS[81,82,161]	2+
Syphilis	47%	1%	Meta[67]	1+
	40%-55%	1%	OS[79,80]	2+
Trichomonas vaginalis	50%	1%	RCT[77]	1+
Mycoplasma genitalium	40%	0.50%	RCT[78]	1+
Herpes simplex virus type 2	30%	4%	RCT[68,69,75,76]	1++
	15%	4%	Meta[67]	1++
Chancroid	50%	< 1%	Meta[67]	1+
Penile cancer (lifetime)	67%	0.07%	Meta[119]	1+
	95%5	0.10%	OS[116]	2+
	95%6	0.11%	OS[117]	2+
	99%6	0.07%	OS[118]	2+
Prostate cancer: Population-based	17%	2.10%	Meta[125]	1+
Black race	42%	17%	Meta[125]	1+
Total percentage of uncircumcised males affected = approximately 80%
B Risks of infant MC
Excessive minor bleeding	–	0.1%–0.2%	OS[128,132]	2++
Infection, local	–	0.06%	OS[128,132]	2++
Infection, systemic	–	0.03%	OS[128]	2++
Need for repeat surgery	–	0.08%	OS[128]	2++
Meatal stenosis	–	< 0.1%	OS[128-131]	2++
Partial loss of penis	–	0.00%	OS[128]	2++
Death	–	< 0.000001%	OS[132]	2++
Reduced penile function, sensitivity, sexual pleasure	–	0%	SR[133,134,137]	2++
Reduced penile function	–	0%	Meta[134]	1+
Total percentage of adverse events from infant circumcision: Approx. 0.4%
Risk vs. benefit
Thus, over the lifetime, the risk to an uncircumcised male of developing a foreskin-related condition requiring medical attention may be up to 80%. In comparison the procedural risk during infant MC of experiencing an easily treatable condition is approximately 1 in 250. The risk of a moderate or serious complication is approximately 1 in 3000. Thus, benefit to risk ratio = 1:200.
C Risks reduced by female partners
Condition7	Decrease in risk7	Study type and ref.	Quality score3
Cervical cancer	58%8	OS[59,60]	2++
	28%	RCT[101]	1++
Herpes simplex virus type 2	55%	OS[102]	2+
Genital ulceration	22%	RCT[103]	1+
Trichomonas vaginalis	48%	RCT[103]	1+
Syphilis	75%	OS[79]	2++
Bacterial vaginosis	40%	RCT[103]	1+
Chlamydia trachomatis	829	OS[104]	1++

¹Based on data for circumcised vs uncircumcised males;

²The percentage of males who will be affected as a result of the single risk factor of retention of the foreskin. Data for STIs were estimated after taking into account the external factor of heterosexual exposure, which is dependent on population prevalence of each STI in North America and risk reduction conferred by circumcision;

³Quality rating was based on an international grading system[13]. Rating was 1++ or 1+ for well-conducted meta-analysis and RCTs, was 2++ for well-conducted systematic reviews, and was 2++ or 2+ for the original studies cited;

⁴Phimosis (tight foreskin) is confined almost exclusively to uncircumcised males;

⁵Penile cancer was 22 times more frequent in uncircumcised males in the Californian study cited[116];

⁶The last two entries for penile cancer are the references cited by the AAP[2] and CDC[5] in their respective circumcision policy statements;

⁷For women with circumcised vs women with uncircumcised sexual partners;

⁸For monogamous women whose male sexual partner has had ≥ 6 other female sexual partners;

⁹Chlamydia trachomatis was 5.6 times more frequent in female partners of uncircumcised males in a large multinational study[104]. Shown are the reference(s) and type of study. The meta-analyses provide comprehensive lists of references to individual studies relevant to the topic. Meta: Meta-analysis; OS: Original study; RCT: Randomized controlled trial; SR: Systematic review; HPV: Human papillomavirus; HIV: Human immunodeficiency virus.