Neutralizing Antibodies to HPV in HIV-Positive MSM
Neutralizing Antibodies to HPV in HIV-Positive MSM
Two hundred ninety-six HIV-positive MSM were included in the analysis. Eighty-six percent of MSM were white and non-Hispanic, 6% MSM were Hispanic, and 8% MSM were "other" (Table 1). The mean age was 42 years and 85% reported having had at "some college" or "college" education. The mean number of years of HIV positivity was 9.5 at the time of the study. Overall 132 of 296 (45%) of the men were seropositive to HPV-16 and 141 of 296 (48%) were seropositive to HPV-18. Seventy-eight of 296 (26%) of the men were positive for both types and 101 of 296 (34%) were seronegative for both. Overall, 175 of 296 (59%) of the men were positive for HPV-16 antibodies or HPV-16 DNA and 167 of 296 (56%) of the men were positive for HPV-18 antibodies or HPV-18 DNA. Conversely, 41% of the men were DNA negative and seronegative to HPV-16 and 44% of the men were DNA negative and seronegative to HPV-18. Twenty-two percent of the men were DNA and seronegative to both HPV-16 and HPV-18.
Titers to HPV-16 in this unvaccinated population were generally less than 1:2000 and titers to HPV-18 were generally less than 1:1000.
There was no relationship between age or ethnic/racial background and rates of seropositivity to HPV-16 or HPV-18 or titers to these HPV types. Although there was no relationship between level of education and rates of seropositivity to HPV-16 or HPV-18, HPV-16 neutralization titers were significantly lower (ptrend = 0.032) among those who reported a college education than those who reported high school or some college education. There was no relationship between years of HIV positivity, current CD4 level, and current HIV viral load, and HPV-16 or HPV-18 seropositivity or titers (Table 2).
There was no relationship between HPV-16 or HPV-18 seropositivity or titers, prevalent anal squamous intraepithelial lesions, or lesion severity (Table 3). History of anogenital warts was associated with higher HPV-18 titers but not overall HPV-16 or HPV-18 seropositivity or HPV-16 titers.
HPV-16 seropositivity was associated with HPV-16 DNA positivity. Seventy-six of 119 (64%) men who were HPV-16 DNA positive were HPV-16 seropositive compared with 56 of 177 (32%) of men who were HPV-16 DNA negative (pFisher exact < 0.001). Likewise, HPV-18 seropositivity was associated with HPV-18 DNA positivity. Fifty-three of 79 (67%) men who were HPV-18 DNA positive were HPV-18 seropositive compared with 88 of 217 (41%) of men who were HPV-18 DNA negative (pFisher exact < 0.001). Compared with those who were HPV-16 DNA negative, there was a significant increase in HPV-16 seropositivity among those who were HPV-16 DNA positive whether or not they were also positive for HPV-18 DNA. HPV-16 seropositivity was not associated with HPV-18 DNA positivity alone. HPV-16 titers were significantly increased among those who were HPV-16 DNA positive and HPV-18 DNA negative compared with those who were HPV-16 and HPV-18 DNA negative.
As with the significant and specific relationship between HPV-16 DNA positivity and HPV-16 seropositivity, there was a significant and specific relationship between HPV-18 DNA positivity and HPV-18 seropositivity. Compared with those who were HPV-16 DNA negative and HPV-18 DNA negative, there was a significant increase in HPV-18 seropositivity among those who were HPV-18 DNA positive and those who were positive for both HPV-16 and HPV-18 DNA. In contrast, HPV-18 seropositivity was not associated with HPV-16 DNA positivity alone in the absence of concurrent HPV-18 positivity. HPV-18 titers were significantly increased among those who were HPV-18 DNA positive but not those who were HPV-16 DNA positive and HPV-18 DNA negative or positive for both HPV-16 and HPV-18 DNA.
HPV-16 DNA signal intensity correlated with the proportion of study participants who were HPV-16 seropositive (ptrend < 0.001) and to a lesser extent, the proportion who were HPV-18 DNA positive (ptrend = 0.013). Higher HPV-16 DNA signal intensity also correlated with higher HPV-16 titers (ptrend = 0.008) but not HPV-18 titers. HPV-18 DNA signal intensity correlated with the proportion of men seropositive for HPV-18 (ptrend < 0.001) and HPV-18 titers (ptrend = 0.003) but not with the proportion who were seropositive for HPV-16 or HPV-16 titers.
A higher number of receptive sexual partners in the last year (ptrend < 0.001), but not lifetime receptive sexual partners, was associated with a higher proportion of HPV-16 seropositivity (Table 4). Both lifetime receptive partners (ptrend = 0.010) and receptive partners within the last year (ptrend = 0.003) were associated with a higher proportion of HPV-18 positivity. The number of receptive partners did not correlate with HPV-16 or HPV-18 titers.
A higher number of lifetime insertive sexual partners (ptrend = 0.004) and insertive sexual partners in the last year (ptrend = 0.006) were associated with a higher proportion of HPV-16 seropositivity, whereas neither insertive partners within the last year nor lifetime insertive partners were associated with a higher proportion of HPV-18 positivity. The number of insertive partners did not correlate with either HPV-16 or HPV-18 titers.
Using selected risk factors shown to be significant in univariate analysis and measures of HIV status, we assembled a multivariable model of risk factors HPV-16 and HPV-18 seropositivity (Table 5). When including years of HIV positivity, current CD4 level, and HIV viral load, risk factors that remained significant for increased risk of HPV-16 seropositivity included positivity for HPV DNA with increasing signal intensity (ptrend < 0.001) and number of receptive partners in the last year (ptrend = 0.012). Risk factors for HPV-18 seropositivity not only included HPV-18 positivity with increasing HPV-18 DNA signal intensity (ptrend < 0.001), and number of receptive partners within the last year (ptrend < 0.001), but also included being older (ptrend = 0.019).
The neutralizing titer levels were significantly higher for HPV-16 (mean = 1148, interquartile range = 1400) than HPV-18 (mean = 758, interquartile range = 650) genotypes (P < 0.0001). However, a statistically significant cubic correlation between HPV-16 and HPV-18 titer levels was not observed (adjusted R = 0.08, P = 0.7629) (see Figure S1, Supplemental Digital Content, http://links.lww.com/QAI/A452).
Results
Relationship Between Study Population Demographics, HIV Disease Status, and HPV Serostatus
Two hundred ninety-six HIV-positive MSM were included in the analysis. Eighty-six percent of MSM were white and non-Hispanic, 6% MSM were Hispanic, and 8% MSM were "other" (Table 1). The mean age was 42 years and 85% reported having had at "some college" or "college" education. The mean number of years of HIV positivity was 9.5 at the time of the study. Overall 132 of 296 (45%) of the men were seropositive to HPV-16 and 141 of 296 (48%) were seropositive to HPV-18. Seventy-eight of 296 (26%) of the men were positive for both types and 101 of 296 (34%) were seronegative for both. Overall, 175 of 296 (59%) of the men were positive for HPV-16 antibodies or HPV-16 DNA and 167 of 296 (56%) of the men were positive for HPV-18 antibodies or HPV-18 DNA. Conversely, 41% of the men were DNA negative and seronegative to HPV-16 and 44% of the men were DNA negative and seronegative to HPV-18. Twenty-two percent of the men were DNA and seronegative to both HPV-16 and HPV-18.
Titers to HPV-16 in this unvaccinated population were generally less than 1:2000 and titers to HPV-18 were generally less than 1:1000.
There was no relationship between age or ethnic/racial background and rates of seropositivity to HPV-16 or HPV-18 or titers to these HPV types. Although there was no relationship between level of education and rates of seropositivity to HPV-16 or HPV-18, HPV-16 neutralization titers were significantly lower (ptrend = 0.032) among those who reported a college education than those who reported high school or some college education. There was no relationship between years of HIV positivity, current CD4 level, and current HIV viral load, and HPV-16 or HPV-18 seropositivity or titers (Table 2).
Relationship Between Anal HPV Infection, Anal Squamous Intraepithelial Lesions, and HPV Serostatus
There was no relationship between HPV-16 or HPV-18 seropositivity or titers, prevalent anal squamous intraepithelial lesions, or lesion severity (Table 3). History of anogenital warts was associated with higher HPV-18 titers but not overall HPV-16 or HPV-18 seropositivity or HPV-16 titers.
HPV-16 seropositivity was associated with HPV-16 DNA positivity. Seventy-six of 119 (64%) men who were HPV-16 DNA positive were HPV-16 seropositive compared with 56 of 177 (32%) of men who were HPV-16 DNA negative (pFisher exact < 0.001). Likewise, HPV-18 seropositivity was associated with HPV-18 DNA positivity. Fifty-three of 79 (67%) men who were HPV-18 DNA positive were HPV-18 seropositive compared with 88 of 217 (41%) of men who were HPV-18 DNA negative (pFisher exact < 0.001). Compared with those who were HPV-16 DNA negative, there was a significant increase in HPV-16 seropositivity among those who were HPV-16 DNA positive whether or not they were also positive for HPV-18 DNA. HPV-16 seropositivity was not associated with HPV-18 DNA positivity alone. HPV-16 titers were significantly increased among those who were HPV-16 DNA positive and HPV-18 DNA negative compared with those who were HPV-16 and HPV-18 DNA negative.
As with the significant and specific relationship between HPV-16 DNA positivity and HPV-16 seropositivity, there was a significant and specific relationship between HPV-18 DNA positivity and HPV-18 seropositivity. Compared with those who were HPV-16 DNA negative and HPV-18 DNA negative, there was a significant increase in HPV-18 seropositivity among those who were HPV-18 DNA positive and those who were positive for both HPV-16 and HPV-18 DNA. In contrast, HPV-18 seropositivity was not associated with HPV-16 DNA positivity alone in the absence of concurrent HPV-18 positivity. HPV-18 titers were significantly increased among those who were HPV-18 DNA positive but not those who were HPV-16 DNA positive and HPV-18 DNA negative or positive for both HPV-16 and HPV-18 DNA.
HPV-16 DNA signal intensity correlated with the proportion of study participants who were HPV-16 seropositive (ptrend < 0.001) and to a lesser extent, the proportion who were HPV-18 DNA positive (ptrend = 0.013). Higher HPV-16 DNA signal intensity also correlated with higher HPV-16 titers (ptrend = 0.008) but not HPV-18 titers. HPV-18 DNA signal intensity correlated with the proportion of men seropositive for HPV-18 (ptrend < 0.001) and HPV-18 titers (ptrend = 0.003) but not with the proportion who were seropositive for HPV-16 or HPV-16 titers.
Relationship Between Sexual Behavior and HPV Serotatus
A higher number of receptive sexual partners in the last year (ptrend < 0.001), but not lifetime receptive sexual partners, was associated with a higher proportion of HPV-16 seropositivity (Table 4). Both lifetime receptive partners (ptrend = 0.010) and receptive partners within the last year (ptrend = 0.003) were associated with a higher proportion of HPV-18 positivity. The number of receptive partners did not correlate with HPV-16 or HPV-18 titers.
A higher number of lifetime insertive sexual partners (ptrend = 0.004) and insertive sexual partners in the last year (ptrend = 0.006) were associated with a higher proportion of HPV-16 seropositivity, whereas neither insertive partners within the last year nor lifetime insertive partners were associated with a higher proportion of HPV-18 positivity. The number of insertive partners did not correlate with either HPV-16 or HPV-18 titers.
Multivariable Model of Risk Factors for HPV-16 or HPV-18 Seropositivity
Using selected risk factors shown to be significant in univariate analysis and measures of HIV status, we assembled a multivariable model of risk factors HPV-16 and HPV-18 seropositivity (Table 5). When including years of HIV positivity, current CD4 level, and HIV viral load, risk factors that remained significant for increased risk of HPV-16 seropositivity included positivity for HPV DNA with increasing signal intensity (ptrend < 0.001) and number of receptive partners in the last year (ptrend = 0.012). Risk factors for HPV-18 seropositivity not only included HPV-18 positivity with increasing HPV-18 DNA signal intensity (ptrend < 0.001), and number of receptive partners within the last year (ptrend < 0.001), but also included being older (ptrend = 0.019).
Association Between HPV-16 and HPV-18 Neutralization Results
The neutralizing titer levels were significantly higher for HPV-16 (mean = 1148, interquartile range = 1400) than HPV-18 (mean = 758, interquartile range = 650) genotypes (P < 0.0001). However, a statistically significant cubic correlation between HPV-16 and HPV-18 titer levels was not observed (adjusted R = 0.08, P = 0.7629) (see Figure S1, Supplemental Digital Content, http://links.lww.com/QAI/A452).
Source...