Neutralizing Antibodies to HPV in HIV-Positive MSM
Neutralizing Antibodies to HPV in HIV-Positive MSM
Objective: Human papillomavirus (HPV) vaccination is routinely recommended in HIV-positive men who have sex with men (MSM) aged ≤26 years. Levels of previous HPV exposure in older HIV-positive MSM are assumed to be too high to warrant routine HPV vaccination. However, little is known about the prevalence of and risk factors for neutralizing antibody seropositivity to HPV-16 or HPV-18, a key measure of previous exposure to these types.
Methods: Cross-sectional analysis of baseline visit for 296 HIV-positive MSM participating in a prospective cohort study of anal squamous intraepithelial lesions at a university-based research clinic. Participants completed a questionnaire detailing behaviors and medical history. Phlebotomy, anal cytology, HPV DNA testing with quantitation, and high-resolution anoscopy with biopsy were performed. A pseudovirion-based neutralizing antibody assay was used to measure HPV-16 and HPV-18 neutralizing antibodies.
Results: One hundred thirty-two of 296 (45%) men were HPV-16 seropositive and 141 of 296 (48%) were HPV-18 seropositive. One hundred seventy-five of 296 (59%) of the men were positive for HPV-16 antibodies or DNA and 167 of 296 (56%) were positive for HPV-18 antibodies or DNA. In multivariable analysis, HPV-16 seropositivity did not correlate with age, years of HIV positivity, CD4 level, or HIV viral load. Significant risk factors included HPV-16 DNA positivity with higher DNA levels (ptrend < 0.001) and higher number of receptive sexual partners in the last year (ptrend = 0.012).
Conclusions: A high proportion of HIV-positive MSM aged >26 years are DNA negative and seronegative to HPV-16 and HPV-18 even when using a sensitive pseudovirion-based neutralizing antibody assay. Prospective studies are needed to determine the clinical- and cost-effectiveness of HPV vaccination in HIV-positive MSM aged >26 years.
Like cervical cancer, anal cancer is associated with human papillomavirus (HPV) infection, particularly HPV-16 and HPV-18. The incidence of anal cancer is increased in certain groups of the population, particularly men who have sex with men (MSM) and those who are immunocompromised due to medication to prevent solid organ transplant rejection or HIV infection. Before the advent of highly active antiretroviral therapy (HAART), the incidence of anal cancer was increased in HIV-positive MSM relative to MSM, but the difference in incidence was modest. It is now clear that the HAART has not led to a reduction in the incidence of anal cancer, with several studies reporting an increase in the incidence of anal cancer in the post-HAART era. The incidence of anal cancer was recently reported to be 131 of 100,000 among HIV-positive MSM and is 80-fold higher in this population than the general population of men.
The quadrivalent HPV (qHPV) vaccine was recently shown to be effective to prevent persistent anal HPV-16 and HPV-18 infection and anal squamous intraepithelial lesions caused by these HPV types in healthy mostly HIV-negative MSM aged 16–26 years. HPV vaccination therefore has the potential to prevent a large percentage of anal cancers.
All the randomized placebo-controlled trials of the bivalent or qHPV vaccines demonstrated their highest efficacy among those considered naive to a given vaccine type, that is, those who were both DNA negative and seronegative to that type. To most accurately assess previous HPV exposure, it is necessary to assess seropositivity to these types because individuals may become DNA test negative over time. An understanding of current or previous exposure to HPV-16 and HPV-18 among HIV-positive MSM older than 26 years is therefore critical to guide vaccination policy in this group given its high incidence of anal cancer.
Several methods have been used to measure seropositivity to HPV. Antibodies to a variety of linear HPV proteins may be measured. More recently, there has been increasing interest in measuring neutralizing antibodies because their presence or absence would presumably best reflect potential for benefit from vaccination. A commonly used method is a competitive Luminex immunoassay (cLIA) that employs a monoclonal antibody to a single L1 neutralizing epitope. Although convenient for high-throughput assays and highly specific, this assay has limited sensitivity given its ability to detect antibodies to only 1 epitope. More recently, enzyme-linked immunosorbent assays (ELISAs) designed to detect a wider array of neutralizing antibodies have been developed to address this limitation.
Here, we report the prevalence of and risk factors for seropositivity to HPV-16 and HPV-18 in a group of HIV-positive MSM using a pseudovirion-based neutralizing antibody (PBNA) assay. Because the PBNA assay likely measures a wider range of antibodies with neutralizing capability than cLIA or ELISAs, it may have higher sensitivity and thus may better reflect previous HPV exposure to HPV-16 and HPV-18. Guidelines of World Health Organization for HPV vaccines have indicated that neutralization assays are the "gold standard" for unbiased assessment of the protective potential of vaccine-induced antibodies.
Abstract and Introduction
Abstract
Objective: Human papillomavirus (HPV) vaccination is routinely recommended in HIV-positive men who have sex with men (MSM) aged ≤26 years. Levels of previous HPV exposure in older HIV-positive MSM are assumed to be too high to warrant routine HPV vaccination. However, little is known about the prevalence of and risk factors for neutralizing antibody seropositivity to HPV-16 or HPV-18, a key measure of previous exposure to these types.
Methods: Cross-sectional analysis of baseline visit for 296 HIV-positive MSM participating in a prospective cohort study of anal squamous intraepithelial lesions at a university-based research clinic. Participants completed a questionnaire detailing behaviors and medical history. Phlebotomy, anal cytology, HPV DNA testing with quantitation, and high-resolution anoscopy with biopsy were performed. A pseudovirion-based neutralizing antibody assay was used to measure HPV-16 and HPV-18 neutralizing antibodies.
Results: One hundred thirty-two of 296 (45%) men were HPV-16 seropositive and 141 of 296 (48%) were HPV-18 seropositive. One hundred seventy-five of 296 (59%) of the men were positive for HPV-16 antibodies or DNA and 167 of 296 (56%) were positive for HPV-18 antibodies or DNA. In multivariable analysis, HPV-16 seropositivity did not correlate with age, years of HIV positivity, CD4 level, or HIV viral load. Significant risk factors included HPV-16 DNA positivity with higher DNA levels (ptrend < 0.001) and higher number of receptive sexual partners in the last year (ptrend = 0.012).
Conclusions: A high proportion of HIV-positive MSM aged >26 years are DNA negative and seronegative to HPV-16 and HPV-18 even when using a sensitive pseudovirion-based neutralizing antibody assay. Prospective studies are needed to determine the clinical- and cost-effectiveness of HPV vaccination in HIV-positive MSM aged >26 years.
Introduction
Like cervical cancer, anal cancer is associated with human papillomavirus (HPV) infection, particularly HPV-16 and HPV-18. The incidence of anal cancer is increased in certain groups of the population, particularly men who have sex with men (MSM) and those who are immunocompromised due to medication to prevent solid organ transplant rejection or HIV infection. Before the advent of highly active antiretroviral therapy (HAART), the incidence of anal cancer was increased in HIV-positive MSM relative to MSM, but the difference in incidence was modest. It is now clear that the HAART has not led to a reduction in the incidence of anal cancer, with several studies reporting an increase in the incidence of anal cancer in the post-HAART era. The incidence of anal cancer was recently reported to be 131 of 100,000 among HIV-positive MSM and is 80-fold higher in this population than the general population of men.
The quadrivalent HPV (qHPV) vaccine was recently shown to be effective to prevent persistent anal HPV-16 and HPV-18 infection and anal squamous intraepithelial lesions caused by these HPV types in healthy mostly HIV-negative MSM aged 16–26 years. HPV vaccination therefore has the potential to prevent a large percentage of anal cancers.
All the randomized placebo-controlled trials of the bivalent or qHPV vaccines demonstrated their highest efficacy among those considered naive to a given vaccine type, that is, those who were both DNA negative and seronegative to that type. To most accurately assess previous HPV exposure, it is necessary to assess seropositivity to these types because individuals may become DNA test negative over time. An understanding of current or previous exposure to HPV-16 and HPV-18 among HIV-positive MSM older than 26 years is therefore critical to guide vaccination policy in this group given its high incidence of anal cancer.
Several methods have been used to measure seropositivity to HPV. Antibodies to a variety of linear HPV proteins may be measured. More recently, there has been increasing interest in measuring neutralizing antibodies because their presence or absence would presumably best reflect potential for benefit from vaccination. A commonly used method is a competitive Luminex immunoassay (cLIA) that employs a monoclonal antibody to a single L1 neutralizing epitope. Although convenient for high-throughput assays and highly specific, this assay has limited sensitivity given its ability to detect antibodies to only 1 epitope. More recently, enzyme-linked immunosorbent assays (ELISAs) designed to detect a wider array of neutralizing antibodies have been developed to address this limitation.
Here, we report the prevalence of and risk factors for seropositivity to HPV-16 and HPV-18 in a group of HIV-positive MSM using a pseudovirion-based neutralizing antibody (PBNA) assay. Because the PBNA assay likely measures a wider range of antibodies with neutralizing capability than cLIA or ELISAs, it may have higher sensitivity and thus may better reflect previous HPV exposure to HPV-16 and HPV-18. Guidelines of World Health Organization for HPV vaccines have indicated that neutralization assays are the "gold standard" for unbiased assessment of the protective potential of vaccine-induced antibodies.
