Baseline sociodemographic characteristics, sexual behaviors, and symptoms of STIs were similar between male study arm participants, except that a greater proportion of men in the intervention arm had previously received voluntary counseling and testing (p=0.008) and more men in the control arm consumed alcohol prior to sexual intercourse (p=0.045) (). The female enrollment characteristics were comparable between study arms for all enrollment covariates examined. At enrollment, the prevalence of HR-HPV was 35.2% (228/648) in the women married to intervention arm men and 37.1% (221/595) in the women married to control arm men (PRR 0.95, 95%CI 0.82-1.10, p =0.479) ().
Baseline characteristics, risk behaviors, and symptoms of sexually transmitted infections of men and their female partners by study arm.
Female HPV prevalence at enrollment, and at 12 and 24 months follow-up, by male circumcision study arm (intention-to-treat analysis).
Throughout the duration of the study, 14 vaginal samples (0.8%, 14/1,758) tested in intervention arm women and 26 (1.6%, 26/1,614) tested in control arm women were excluded from the analyses because of the absence of detectable beta-globin and HPV DNA (). This difference in DNA detection was statistically significant (p=0.04). There were 34 male intervention arm crossovers who did not accept surgery by one year after randomization. There were 7 male control arm crossovers at year one and 11 male control arm crossovers at year two who received MC from other sources.
In the primary intention-to-treat analyses, the prevalence of female HR-HPV infection at year two was 27.8% (151/544) in the intervention arm and 38.7% (189/488) in the control arm (PRR = 0.72, 95% CI 0.60-0.85, p=0.001) (). In an as treated analysis, the prevalence of any HR-HPV infections at year two was 28.4% (148/521) in spouses of circumcised men and 37.8% (192/508) in spouses of uncircumcised men (PRR = 0.75, 95% CI 0.63-0.90, p= 0.002) (). HR-HPV declined from 35.2% (228/648) at enrollment to 27.8% (151/544) at year 2 (Δ −7.4%, p=0.006) in female partners of men in the intervention arm but remained unchanged in female partners of men in the control arm (Δ +1.6%, p=0.59).
Female HPV prevalence at enrollment, and at 12 and 24 months follow-up, by male circumcision status (as treated analysis).
The incidence of new HPV infections is shown in . Over the two-year follow-up, the incidence of HR-HPV was 20.7/100 py in intervention arm wives and 26.9/100 py in control arm wives (IRR= 0.77, 95% CI 0.63-0.93, p=0.008). The incidence of low-risk HPV (LR-HPV) was also reduced among the wives of circumcised men (IRR=0.83, 95% CI 0.69-1.00, p=0.05). New detection of multiple HR-HPV genotypes (IRR= 0.71, 95% CI 0.53-0.95, p=0.02) and multiple LR-HPV genotypes (IRR= 0.65, 95%CI 0.49-0.87, p=0.003) was lower among women married to men in the intervention arm. Although the incidence of single HR-HPV infections in female partners of intervention arm men was lower compared with partners of control arm men, the difference was not statistically significant.
Female HPV incidence by study arm and follow-up interval for participants with amplifiable cellular and/or viral DNA at sequential study visits. N is the number of women with newly detected HPV infections.
The incidence of genotype-specific HR-HPV infection (including HPV 16) over 24 months was lower in the wives of intervention than control arm men for all HR-HPV genotypes examined, except for HPV 39 (). However, only HPV 33, 35 and 58 genotype-specific differentials were statistically significant. The incidence of LR-HPV genotype 6 and 11 was also assessed since these two genotypes are associated with genital warts, and MC significantly reduced HPV 11 in female partners (IRR 0.20, 95% CI 0.06-0.72, p=0.006), but had no effect on HPV 6 in female partners (IRR 1.04, 95% CI 0.65-1.67, p=0.87), as shown in Supplemental Table 1
Genotype-specific female HR-HPV incidence over two years by study arm. N is the number of women with newly detected genotypes.
The two-year cumulative rates of new HR-HPV detection per 100 person-years by sociodemographic and sexual behavioral characteristics and symptoms of sexually transmitted infections are shown in . The incidence of HR-HPV infection in female partners of men in the intervention arm was lower than in the wives of control arm men in all sociodemographic/behavioral subgroups, except for women reporting non-marital relationships and symptoms of dysuria. After adjustment for enrollment characteristics (age, condom use, alcohol consumption with sex, and number of sex partners during the past year), and controlling for correlation due to polygynous unions, the adjusted IRR of any new HR-HPV detection in female partners of intervention relative to control men was IRR=0.77 (95%CI 0.65-0.92, p=0.004).
Table 6 Female HR-HPV incident infection and incidence rate ratios over two year follow-up by enrollment sociodemographic and behavioral characteristics and symptoms of sexually transmitted infection reported during the year prior to enrollment. N is the number (more ...)
As shown in , the cumulative probability of genotype-specific HR-HPV clearance (i.e., loss of detection) among women who were prevalent positive at enrollment was higher among the wives of men in the intervention arm (66.2%, 376/568) than wives of control arm men (59.2%, 339/573, RR=1.12, 95% CI 1.02-1.22, p=0.014). The proportion of genotype-specific cleared infections was higher in the intervention arm women for 10 of the 14 (71.4%) HR-HPV genotypes (). However, clearance of HPV16 was not increased. After adjustment for baseline age, education, number of sex partners, alcohol consumption with sex, condom use, and accounting for possible correlation of one woman clearing multiple genotypes, the HR-HPV clearance risk ratio in female partners of men in the intervention relative to the control arm was 1.10 (95% CI 1.03-1.20, p =0.003). The clearance probability at year two among women who acquired HR-HPV genotypes during the first year of the trial was also higher among intervention arm wives (82.1%, 124/151) compared to control arm wives (70.2%, 127/181, RR=1.17, 95%CI 1.04-1.32, p=0.014). Results were similar for genotype-specific LR-HPV clearance (Supplemental Table 2
Table 7 Clearance of pre-existing genotype-specific female HR-HPV infections by study arm. The denominators (N) are individuals with the specified genotype who had amplifiable cellular and/or viral DNA at both enrollment and follow-up, and were positive for the (more ...)
Self-reported rates of female partners’ sexual practices and STI symptoms were assessed by the male partner’s circumcision status (Supplemental Table 3
). At year one, there were no differences in behaviors or STI symptoms between the two arms. At year two, the rate of female self-reported GUD was significantly lower in the female partners of intervention arm men (12.8%, 70/549) compared to women with control arm partners (17.1%, 86/502, p=0.046). In addition, the proportion of women reporting inconsistent condom use during the second year of follow-up was higher in the control than intervention arm (p=0.022). There were no differences in the reported number of sexual partners, non-marital relationships, vaginal discharge, or dysuria between the women in the two study arms at either year one or year two. Among the male partners, there were no reported differences in the number of sexual partners, non-marital relationships or condom use between study arms at enrollment and during follow-up.