Prevalence of HPV in Men Who Have Sex With Men
Prevalence of HPV in Men Who Have Sex With Men
Objectives The incidence of human papillomavirus (HPV)-associated anal cancer is increasing. Men who have sex with men (MSM), particularly those coinfected with HIV, are disproportionately affected. Documenting the molecular epidemiology of HPV infection is important in guiding policy makers in formulating universal and/or targeted vaccine guidelines.
Methods A prospective cohort study was conducted. HIV-positive and HIV-negative MSM > 18 years old were invited to participate. Provider-performed anal swabs were collected and anal HPV infection was detected using consensus primer solution phase polymerase chain reaction (PCR) followed by type-specific PCR for high-risk (HR)-HPV types 16, 18 and 31. Between-group differences were analysed using χ tests and Wilcoxon rank tests.
Results One hundred and ninety-four MSM [mean (standard deviation (SD)) age 36 (10) years; 51% HIV-positive) were recruited. The median number of sexual contacts in the preceding 12 months was 4 (interquartile range 2–10). HIV-positive subjects had a mean (SD) CD4 count of 557 (217) cells/μL, and 84% were on highly active antiretroviral therapy (HAART). Thirty-one samples were B-globin negative and thus excluded from further analysis. A total of 113 subjects (69%) had detectable HPV DNA. Sixty-eight subjects (42%) had an HR-HPV type detected. HR HPV type 16 was detected in 44 samples (27%), HR-HPV type 18 in 26 samples (16%) and HR-HPV type 31 in 14 samples (23%). Twenty-eight subjects (17%) had more than one type of HR-HPV type detected. When HPV and HR-HPV were stratified by age, those > 35 years had a higher prevalence (P = 0.001 and P = 0.028, respectively). HIV-positive subjects were more likely than HIV-negative subjects to have any detectable HPV (77% vs. 61%, respectively; P = 0.04), to have HR-HPV type 18 or 31 (P = 0.05 and P = 0.006, respectively) and to be infected with more than one HR-HPV type (31% vs. 3%, respectively; P < 0.001). Within the HIV-positive group, the prevalence of HPV was higher in those not on HAART (P = 0.041), although it did not differ when stratified by CD4 count.
Conclusions The identified prevalence of anal HPV infection was high. Emerging patterns of HPV-related disease strengthen the call for universal vaccination of boys and girls with consideration of catch-up and targeted vaccination of high-risk groups such as MSM and those with HIV infection.
Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI); it is highly prevalent in the sexually active population and is rapidly acquired after sexual debut. Over 90 serotypes of HPV have been identified; low-risk (LR)-HPV types (predominantly 6 and 11) can cause genital warts, while high-risk (HR)-HPV types (predominantly 16 and 18) can cause cancer of the cervix, anus and oropharynx.
Following the introduction of screening programmes in the developed world, the incidence of cervical cancer has decreased; however, the incidences of HPV-associated anal and oropharyngeal cancers have increased dramatically in the past decade. Noncervical HPV-associated cancers, while individually relatively rare, now collectively parallel the burden of cervical cancers in developed countries. HR-HPV is now thought to cause over 5% of all cancers world-wide.
Certain 'at-risk' groups such as men who have sex with men (MSM), particularly those with HIV infection, are disproportionately affected. The incidence of anal cancer is 1–2/100 000 in the general population, 35/100 000 in HIV-negative MSM and up to 70/100 000 in HIV-positive MSM.
Since the advent of highly active antiretroviral therapy (HAART), the HIV-positive population is living longer. In the Department of GU Medicine and Infectious Diseases (GUIDE), the largest HIV centre in Ireland, HIV-related mortality has fallen over tenfold from 16.8 deaths per 100 active patient-years in 1995 to 1.4 deaths per 100 active patient-years in 2012. With increased survival there are an increasing number of non- AIDS-defining illnesses contributing to morbidity and mortality. Malignancy and in particularly anal cancer is a major driver of this trend.
Strategies to curtail the increase in anal cancer include screening, the benefits of which remain to be determined, and HPV vaccination.
Two vaccines have been developed to protect against HPV infection, a quadrivalent vaccine which targets HPV 6, 11, 16 and 18 (Gardasil®, HPV-6/11/16/18, Merck, Whitehouse Station, NJ, USA) and a bivalent vaccine which targets HPV 16 and 18 (Cervarix®, HPV-16/18, GlaxoSmithKline Biologicals, GSK, Brentford, London, UK).
Both vaccines have demonstrated efficacy against the development of cervical intraepithelial neoplasia (CIN) 2 or 3, adenocarcinoma in situ or cervical cancer among HPV-naïve women. Gardasil has in addition demonstrated efficacy against genital warts in male and female individuals and anal intraepithelial neoplasia related to HPV 6, 11, 16 and 18 in male individuals.
Despite the substantial clinical benefit of the HPV vaccine in male individuals, mathematical models suggest that HPV vaccination of male individuals would exceed cost-effectiveness thresholds. Cost effectiveness, however, has been demonstrated in models looking at specific 'at-risk' male populations such as MSM and those infected with HIV over a range of assumptions.
Although no therapeutic benefit of the HPV vaccine has been demonstrated for the treatment of active disease present at the time of vaccination, there are early data suggesting a possible benefit of HPV vaccination in the setting of previous disease which could represent an important opportunity for intervention in older high-risk patient groups such as HIV-positive MSM.
In addition, if the HPV vaccine proved efficacious in the HIV-positive population against vaccine subtypes, the potential reduction in anal cancer rates could be upwards of 60%.
The primary objective of this study was to document the prevalence of anal HPV infection and the prevalence of infection with HR-HPV types 16, 18 and 31 in HIV-positive and HIV-negative MSM. Secondary objectives were to identify factors associated with HPV and HR-HPV infection.
Understanding the prevalence of HPV and HR-HPV infection in the MSM population may help inform strategies for primary and secondary prevention of HPV-associated anal cancer in this at-risk group.
Abstract and Introduction
Abstract
Objectives The incidence of human papillomavirus (HPV)-associated anal cancer is increasing. Men who have sex with men (MSM), particularly those coinfected with HIV, are disproportionately affected. Documenting the molecular epidemiology of HPV infection is important in guiding policy makers in formulating universal and/or targeted vaccine guidelines.
Methods A prospective cohort study was conducted. HIV-positive and HIV-negative MSM > 18 years old were invited to participate. Provider-performed anal swabs were collected and anal HPV infection was detected using consensus primer solution phase polymerase chain reaction (PCR) followed by type-specific PCR for high-risk (HR)-HPV types 16, 18 and 31. Between-group differences were analysed using χ tests and Wilcoxon rank tests.
Results One hundred and ninety-four MSM [mean (standard deviation (SD)) age 36 (10) years; 51% HIV-positive) were recruited. The median number of sexual contacts in the preceding 12 months was 4 (interquartile range 2–10). HIV-positive subjects had a mean (SD) CD4 count of 557 (217) cells/μL, and 84% were on highly active antiretroviral therapy (HAART). Thirty-one samples were B-globin negative and thus excluded from further analysis. A total of 113 subjects (69%) had detectable HPV DNA. Sixty-eight subjects (42%) had an HR-HPV type detected. HR HPV type 16 was detected in 44 samples (27%), HR-HPV type 18 in 26 samples (16%) and HR-HPV type 31 in 14 samples (23%). Twenty-eight subjects (17%) had more than one type of HR-HPV type detected. When HPV and HR-HPV were stratified by age, those > 35 years had a higher prevalence (P = 0.001 and P = 0.028, respectively). HIV-positive subjects were more likely than HIV-negative subjects to have any detectable HPV (77% vs. 61%, respectively; P = 0.04), to have HR-HPV type 18 or 31 (P = 0.05 and P = 0.006, respectively) and to be infected with more than one HR-HPV type (31% vs. 3%, respectively; P < 0.001). Within the HIV-positive group, the prevalence of HPV was higher in those not on HAART (P = 0.041), although it did not differ when stratified by CD4 count.
Conclusions The identified prevalence of anal HPV infection was high. Emerging patterns of HPV-related disease strengthen the call for universal vaccination of boys and girls with consideration of catch-up and targeted vaccination of high-risk groups such as MSM and those with HIV infection.
Introduction
Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI); it is highly prevalent in the sexually active population and is rapidly acquired after sexual debut. Over 90 serotypes of HPV have been identified; low-risk (LR)-HPV types (predominantly 6 and 11) can cause genital warts, while high-risk (HR)-HPV types (predominantly 16 and 18) can cause cancer of the cervix, anus and oropharynx.
Following the introduction of screening programmes in the developed world, the incidence of cervical cancer has decreased; however, the incidences of HPV-associated anal and oropharyngeal cancers have increased dramatically in the past decade. Noncervical HPV-associated cancers, while individually relatively rare, now collectively parallel the burden of cervical cancers in developed countries. HR-HPV is now thought to cause over 5% of all cancers world-wide.
Certain 'at-risk' groups such as men who have sex with men (MSM), particularly those with HIV infection, are disproportionately affected. The incidence of anal cancer is 1–2/100 000 in the general population, 35/100 000 in HIV-negative MSM and up to 70/100 000 in HIV-positive MSM.
Since the advent of highly active antiretroviral therapy (HAART), the HIV-positive population is living longer. In the Department of GU Medicine and Infectious Diseases (GUIDE), the largest HIV centre in Ireland, HIV-related mortality has fallen over tenfold from 16.8 deaths per 100 active patient-years in 1995 to 1.4 deaths per 100 active patient-years in 2012. With increased survival there are an increasing number of non- AIDS-defining illnesses contributing to morbidity and mortality. Malignancy and in particularly anal cancer is a major driver of this trend.
Strategies to curtail the increase in anal cancer include screening, the benefits of which remain to be determined, and HPV vaccination.
Two vaccines have been developed to protect against HPV infection, a quadrivalent vaccine which targets HPV 6, 11, 16 and 18 (Gardasil®, HPV-6/11/16/18, Merck, Whitehouse Station, NJ, USA) and a bivalent vaccine which targets HPV 16 and 18 (Cervarix®, HPV-16/18, GlaxoSmithKline Biologicals, GSK, Brentford, London, UK).
Both vaccines have demonstrated efficacy against the development of cervical intraepithelial neoplasia (CIN) 2 or 3, adenocarcinoma in situ or cervical cancer among HPV-naïve women. Gardasil has in addition demonstrated efficacy against genital warts in male and female individuals and anal intraepithelial neoplasia related to HPV 6, 11, 16 and 18 in male individuals.
Despite the substantial clinical benefit of the HPV vaccine in male individuals, mathematical models suggest that HPV vaccination of male individuals would exceed cost-effectiveness thresholds. Cost effectiveness, however, has been demonstrated in models looking at specific 'at-risk' male populations such as MSM and those infected with HIV over a range of assumptions.
Although no therapeutic benefit of the HPV vaccine has been demonstrated for the treatment of active disease present at the time of vaccination, there are early data suggesting a possible benefit of HPV vaccination in the setting of previous disease which could represent an important opportunity for intervention in older high-risk patient groups such as HIV-positive MSM.
In addition, if the HPV vaccine proved efficacious in the HIV-positive population against vaccine subtypes, the potential reduction in anal cancer rates could be upwards of 60%.
The primary objective of this study was to document the prevalence of anal HPV infection and the prevalence of infection with HR-HPV types 16, 18 and 31 in HIV-positive and HIV-negative MSM. Secondary objectives were to identify factors associated with HPV and HR-HPV infection.
Understanding the prevalence of HPV and HR-HPV infection in the MSM population may help inform strategies for primary and secondary prevention of HPV-associated anal cancer in this at-risk group.
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