The aim of this study was to systematically review the findings of publications addressing the epidemiology of anal human papillomavirus (HPV) infection, anal intraepithelial neoplasia, and anal cancer in women. We conducted a systematic review among publications published from Jan. 1, 1997, to Sept. 30, 2013, to limit to publications from the combined antiretroviral therapy era. Three searches were performed of the National Library of Medicine PubMed database using the following search terms: women and anal HPV, women anal intraepithelial neoplasia, and women and anal cancer. Publications were included in the review if they addressed any of the following outcomes: (1) prevalence, incidence, or clearance of anal HPV infection, (2) prevalence of anal cytological or histological neoplastic abnormalities, or (3) incidence or risk of anal cancer. Thirty-seven publications addressing anal HPV infection and anal cytology remained after applying selection criteria, and 23 anal cancer publications met the selection criteria. Among HIV-positive women, the prevalence of high-risk (HR)–HPV in the anus was 16–85%. Among HIV-negative women, the prevalence of anal HR-HPV infection ranged from 4% to 86%. The prevalence of anal HR-HPV in HIV-negative women with HPV-related pathology of the vulva, vagina, and cervix compared with women with no known HPV-related pathology, varied from 23% to 86% and from 5% to 22%, respectively. Histological anal high-grade squamous intraepithelial lesions (anal intraepithelial neoplasia 2 or greater) was found in 3–26% of the women living with HIV, 0–9% among women with lower genital tract pathology, and 0–3% for women who are HIV negative without known lower genital tract pathology. The incidence of anal cancer among HIV-infected women ranged from 3.9 to 30 per 100,000. Among women with a history of cervical cancer or cervical intraepithelial neoplasia 3, the incidence rates of anal cancer ranged from 0.8 to 63.8 per 100,000 person-years, and in the general population, the incidence rates ranged from 0.55 to 2.4 per 100,000 person-years. This review provides evidence that anal HPV infection and dysplasia are common in women, especially in those who are HIV positive or have a history of HPV-related lower genital tract pathology. The incidence of anal cancer continues to grow in all women, especially those living with HIV, despite the widespread use of combined antiretroviral therapy.
Squamous cell cancer of the anus (SCCA) incidence has been increasing over the past several decades among women and men. Historically women have had a higher incidence of anal cancer than men, and recent publications have shown that the incidence rate for cancers of the anus, anal canal, and anorectum in all ages and races of women has more than doubled, with an increase from 0.946 per 100,000 in 1975 to 1.827 per 100,000 in 2008. It is estimated that 3000 cases of anal cancer related to human papillomavirus (HPV) occur in women in the United States each year.
Recently many epidemiological studies have highlighted the increase in anal cancer of certain subpopulations of men; specifically, men who have sex with men and HIV-positive individuals have a significantly higher incidence of cancer compared with the general population. There have been fewer publications addressing the changing epidemiology of anal cancer among women, and these publications have demonstrated that the risk of anal cancer has significantly increased among HIV-positive women, with the incidence of anal cancer in HIV-positive women increasing from 0 between 1980 and 1989 to approximately 11 per 100,000 in the years between 1996 and 2004. Thus, SCCA is a growing problem for women in the United States, especially those who are HIV positive.
SCCA shares biological similarities with cervical cancer, including detectable precancerous lesions and high-risk (HR) HPV infection. HPV has been detected in 99% of cervical cancers and 80–90% of anal cancers, with HR HPV types 16 or 18 detected in about 70% of cervical and 80% of anal cancers. Thus, anal HPV infection, in conjunction with other yet-to-be determined factors, leads to the development of high-grade squamous anal intraepithelial lesion (anal intraepithelial neoplasia [AIN] 2 or greater), a likely precursor to anal cancer.
Because programmatic screening for cervical cancer with cytology has been associated with markedly decreased incidence and mortality of cervical cancer, anal cytology (from a Dacron swab inserted into the anal canal) has been evaluated as a screening method for anal neoplasia. Individuals with abnormal anal screening cytology are referred for a colposcopic evaluation of the anus called high-resolution anoscopy (HRA) in which the anal canal is examined with a colposcope after the application of 5% acetic acid and/or lugol solution and lesions are biopsied for histological diagnosis.
A growing body of literature has utilized screening of the anal canal using HRA and anal detection of HPV. However, the majority of literature evaluating the epidemiology of anal HPV infection, anal neoplasia, and anal cancer has focused on HIV-positive men who have sex with men.
Materials and methods
Objective
The aim of this paper is to systematically review and to summarize the findings of publications addressing the epidemiology of anal HPV infection, anal neoplasia, and anal cancer in women.
Methods
We performed a systematic review for publications of anal HPV infection, anal histological and cytological abnormalities in women, and anal cancer in women published from January 1997 to Sept. 30, 2013. Because the publications evaluating HPV-related disease were so heterogeneous (different methodologies for HPV testing, different types of publications, different types of cohorts) and because we wanted to include as many publications as possible to get a full perspective of the research that has been done to date, we conducted a systematic review rather than a metaanalysis. We confined the search to publications published after Jan. 1, 1997, to limit the publications to the combined antiretroviral therapy (cART) era.
Information sources and search strategy
We performed 3 searches of the National Library of Medicine PubMed database using the following search terms: women and anal HPV, women and anal intraepithelial neoplasia, and women and anal cancer. The searches were limited to humans, published in the English language with full text available during the time period specified.
The searches produced a total of 798 manuscripts. After duplicate papers, review papers, and other nonrelevant papers were removed, a total of 535 papers remained for screening. We also enriched the search by examining germane journals and reviewed reference lists from retrieved publications to identify additional manuscripts not captured by the searches. Seven additional manuscripts were identified as meeting inclusion criteria through this method.
Study selection criteria
All potentially relevant publications were then evaluated by 4 individuals and were included in this review if they addressed any of the following outcomes: (1) prevalence, incidence, or clearance of anal HPV infection; (2) prevalence of anal cytological or histological neoplastic abnormalities; or (3) incidence or risk of anal cancer. Publications were excluded if they were case reports, did not include original data, did not include women, or did not stratify data by sex or did not report results related to the aforementioned outcomes. Initial search terms yielded 244 publications for anal HPV infection and cytological and histological pathology; 37 publications addressing anal HPV infection and anal cytology remained after applying selection criteria, with 23 publications that presented findings on both outcomes. Two hundred ninety-one publications were identified for the anal cancer search terms, of which 23 met selection criteria ( Figure ).
Data extraction
For all publications, we recorded the following variables: study location, years of study, methodology, number of participants, and a description of the study population including HIV status. We grouped together publications from the same cohort or population in our tables when appropriate and included the most recent and complete prevalence data presented. The final column in each table allowed us to present the unique findings from each publication.
For publications evaluating HIV-positive women, we recorded the effect of HIV viral load on HPV detection, cytological or histological outcomes based on whichever the primary outcome was reported in the paper. For the anal HPV publications, we recorded the method of HPV testing, incidence/prevalence findings, and concurrent cervical HPV testing findings, if available.
Methods of HPV testing included polymer chain reaction (PCR) and hybrid capture 2 (HC2). The publications varied by overall HPV types detected (high risk or oncogenic HPV genotypes only or high risk combined with low risk) as well as which specific HPV genotypes were included. Of note, there is lack of standardization of HPV testing in the anus (as in the cervix). HPV testing by PCR allows for the identification of specific high- and low-risk HPV genotypes, but HC2 testing does not allow for HPV genotyping; only aggregate data for high-risk genotypes or low-risk genotypes are available through HC2 tests. In addition, PCR has been shown to have a higher sensitivity for detecting low-level HPV infection compared with HC2.
For the anal cytology publication, we recorded prevalence of abnormal anal cytology findings, criteria for undergoing HRA, number of individuals who received HRA, and prevalence of abnormal histological findings. Several publications evaluated both anal HPV prevalence and prevalence of abnormal anal cytology. For those publications that presented both outcomes, we divided the outcomes and presented the HPV findings with all the other HPV publications and the cytology findings with the other cytology publications. For the anal cancer publications, we recorded the anal cancer incidence described in each publication and included the standardized incidence ratio if available and other factors associated with increased incidence of anal cancer identified by the publication.
Results
Study characteristics
A total of 60 publications were included in the review. Many of the publications were conducted in women with specific risk factors for anal cancer. Of the anal HPV prevalence publications, 10 publications specified that the population included only HIV-positive women.
Among the publications that did not specify HIV infection, 6 publications were conducted in women with a history of abnormal cervical cytology or intraepithelial neoplasia (IN) 1 or greater of the lower genital tract, 1 publication was conducted among women with non-HIV related immune suppression, and 9 publications were conducted in the general female population.
Among the publications evaluating anal cytological findings, 14 publications evaluated study cohorts of HIV-positive women, 12 publications evaluated study cohorts of women with abnormal cervical cytology or IN1+ of the lower genital tract; and 7 publications assessed anal cytology among the general population. Among the anal cancer publications, there were 7 publications among HIV-positive women, 7 publications evaluated women with a history of HPV-related disease of the vulva or cervix, and 9 publications included women from the general population.
Synthesis of results
Anal HPV infection in HIV-positive women
There were 10 publications, utilizing 7 different study cohorts, that specifically evaluated the prevalence and/or incidence of anal HPV infection in HIV-positive women ( Table 1 ). With the exception of 2 papers, all publications reported data on HR HPV.
| Study | Location | Years of study | Study design | Subjects, n | Population (age) a | Methodology for HPV testing | Anal HR HPV prevalence, n (%) | Cervical HR HPV prevalence, n (%) | HPV concordance between the anus and cervix, principal HPV types, and notable findings |
|---|---|---|---|---|---|---|---|---|---|
| Durante et al | United States | 1995–1998 | Baseline data from cohort study | 86 | HIV positive with negative anal cytology (mean, 38) | PCR b | 38 (44) | 27 (31) |
|
| Goncalves et al | Brazil | 1996–1997 | Cross-sectional | 102 | HIV positive | PCR c | 44 (43) | 51 (37) |
|
| Hessol et al 2009 Hessol et al 2013 | United States | 2001–2003 | Point prevalence data within a cohort study | 470 | HIV positive/WIHS | PCR d | 188 (40) | 81 (17) |
|
| Kojic et al | United States | 2004–2006 | Baseline data from cohort study | 120 | HIV positive/SUN (median, 38) | PCR e | 102 (85) | 84 (70) |
|
| Tandon et al Baranoski et al | United States | 2006–2010 | Baseline prevalence and incidence data from cohort study | 100 | HIV positive (mean, 40) | HC2 | 16 (16) f | 24 (24) |
|
| The following publications did not separate the findings based on LR vs HR HPV | |||||||||
| Mullins et al Moscicki et al, 2003 | United States | 1996–2001 | Cohort study | 183 | HIV positive adolescent (REACH) (mean, 17) | PCR (HR and LR) | 59 (32) g | — |
|
| Palefsky et al | United States | 1995–1997 | Point prevalence data within a cohort study | PCR: 223 HC2: 242 | HIV positive/WIHS (mean, 40) | PCR (HR and LR) HC2 (HR and LR) | 170 (76) g 182 (75) g | 106 (53) |
|
a Mean or median age reported when available
b HR types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, and 73
c HR types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82
d HR types 16, 18, 31, 33, 39, 45, 51, 52, 56, 58, 59, and 66
e HR types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 70, 73, 82, and IS39
f HR types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68
The prevalence of anal HR HPV was calculated from baseline, point prevalence, or cross-sectional data from the 7 study cohorts. Two publications calculated incidence of new anal HPV infections from cohort studies. Six of the 7 study cohorts were from the United States.
Most publications used PCR to test for HPV, although the publications differed in HPV types detected ( Table 1 footnotes). Three publications utilizing PCR combined low-risk (LR) and HR HPV for their prevalence data. One publication used both PCR and a HC2 test, and 1 cohort used HC2 only.
Prevalence of HPV in the anus (16–85%) was higher than that of the cervix (17–70%) in the majority of publications. Concordant HPV genotypes between the anus and cervix were found in 9–16% of HIV-positive women (compared with only 2% having concordant HPV genotypes in the HIV-matched cohorts).
The most common prevalent HPV types identified in the anus were 16, 53, 45, 52, 18, and 35 (compared with the concurrent cervical HPV types 16, 52, 53, 58, and 31). Baranoski et al reported the incidence of new anal HR HPV infections was 74 per 1,000 person-years for HIV-positive women over an average follow-up time of 704 days.
Risk factors for prevalent anal HPV included cervical HPV, CD4 less than 200, smoking, and perianal warts. CD4 500 or greater was shown to be significantly protective for anal HPV infection. Of note, reported history of anal intercourse was not associated with anal HPV. Only 1 publication, by Palefsky et al evaluated the effect of most current HIV viral load on the detection of both high-risk and low-risk HPV types by both hybrid capture and PCR and did not find any differences in the detection of HPV using either method between individuals with high HIV viral load compared with low HIV viral load.
Anal HPV infection in predominantly HIV-negative female cohorts
Eighteen publications (representing 13 different study cohorts) reported data on anal HPV prevalence, incidence, or clearance in women not known to be HIV positive ( Table 2 ). The 13 study cohorts varied widely by age, recruitment criteria, population pool, and other inclusion criteria. Six of the cohorts were recruited from women attending colposcopy clinics ; however, the inclusion criteria among these cohorts varied from an abnormal referral cervical cytology, to histological cervical intraepithelial neoplasia (CIN) 3+.
| Study | Location | Years of Study | Study design | Subjects, n | Population (age) a | Methodology for HPV testing | Anal HR HPV prevalence, n (%) b | Cervical HR HPV prevalence, n (%) b | HPV concordance between the anus and cervix, principal HPV types, and notable findings |
|---|---|---|---|---|---|---|---|---|---|
| Park et al | United States | 2006–2007 | Cross-sectional | 92 | IN2+ lower genital tract (including Ca) (HIV positive: n = 1) (mean, 32) | PCR | 33 (36) c | — |
|
| Valari et al | Greece | 2009–2011 | Cross-sectional | 235 | IN1 or greater (including cervical Ca, n =20, and vulva Ca, n =1) (mean, 34) | PCR mRNA (flow) | 72 (31) d 19 (8) e | 91 (39) 60 (26) |
|
| Véo et al | Brazil | — | Cross-sectional | 40 | CIN3 (mean, 33) | HC2 | 9 (23) f | 39 (98) |
|
| 40 | Gynecology clinic (no CIN 3) (mean, 40) | HC2 | 2 (5) f | 3 (8) | |||||
| Goodman et al, 2008 ; Shvetsov | United States | 1998–2003 | Cohort study | 431 | Subset of Hernandez (2005) g (mean, 39) | PCR | 96 (22) h | 143 (33) |
|
| Goodman et al, 2010 | United States | 1998–2008 | Cohort study | 751 | Subset of Hernandez (2005) g (mean, 34) | PCR | — | — |
|
| Hernandez et al, 2013 | United States | 2008–2009 | Cross-sectional | 211 | Women, community (mean, 40) | PCR | 8 (4) i | 11 (5) |
|
| Pierangeli et al | Italy | 2005–2011 | Cross-sectional | 134 | HIV negative, proctology clinic j (mean, 42) | PCR | 18 (13) k | 13/108 (12) |
|
| Hessol et al, 2009 Hessol et al, 2013 | United States | 2001–2003 | Point prevalence within a cohort study | 185 | HIV negative (WIHS) (mean, 29) | PCR | 28 (15) | 13 (1) |
|
| The following publications did not separate the findings based on LR vs HR HPV | |||||||||
| D’Hauwers et al | Belgium | 2007–2008 | Cross-sectional | 96 | Colposcopy clinic (n = 61 ) Gynecology clinic (n = 35 ) (mean, 30) | PCR (HR and LR) | HR and LR 54 (56) b,l | HR and LR 59 (61) b |
|
| Crawford et al | United Kingdom | 2009–2010 | Cross-sectional | 100 | Colposcopy clinic (mean, 34) | PCR (HR and LR) HPV16 HPV31 | 84 (90) b,m,n 52/93 (56) 20/93 (22) | 96 (96) b 55 (53) 24 (24) |
|
| Heraclio et al | Brazil | 2008–2009 | Cross-sectional | 303 | CIN1 or greater (including cervical Ca, n = 26) (HIV positive, n = 8) | PCR (LR and HR) | 255 (84) b,o | — | — |
| Castro et al | Costa Rica | 2004–2005 | Cross-sectional | 2107 | Women, community (22–29 y) | PCR HR and LR PCR HR only | 666 (32) b 464 (22) p | 768 (36) b n/a |
|
| Hernandez et al, 2005 | United States | 1998–2004 | Baseline data from cohort study | 1378 | Women, community | PCR (LR and HR) | 368 (27) b,q | 368 (27) b |
|
| Mullins et al Moscicki et al, 2003 | United States | 1996–2001 | Cohort study | 82 | HIV negative adolescent (REACH) (mean, 17) | PCR (HR and LR) | 11 (13) b | — |
|
| Palefsky et al | United States | 1995–1997 | Point prevalence within a cohort study | PCR: 57 HC2: 67 | HIV-negative subset of WIHS (mean, 40) | PCR (HR and LR) HC2 (HR and LR) | 24 (42) b,r HC2: 20 (30) | 12 (24) | — |
a Mean or median age reported when available
b Publications reporting only combined HR and LR HPV data (and not separating out the HR HPV) are as follows: Castro et al, Crawford et al, D’Hauwers et al, Goodman et al (2010), Heraclio et al, Hernandez et al, and Palefsky et al
c HR types 16, 18, 26, 31, 33, 35,39, 45, 51–53, 56, 58, 59, 66, 68, 73, 82, and IS39
e Flow cytometry for E6 and 7 mRNA of 14 high-risk HPV types (not stated)
g Note that these publications are a subset of the cohort from Hernandez et al (2005) with sufficient follow-up
h HR types 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73, and 82
i HR types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68
j Cohort has no history of HPV-related pathologies
k HR types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68; possible HR 26, 34, 53, 66, 70, 73, and 82
l HR types 6 E6, 11 E6, 16 E7, 18 E7, 31 E6, 33 E6, 35 E6, 39 E7, 45 E7, 51 E6, 52 E7, 53 E6, 56 E7, 58 E6, 59 E7, 66 E6, 67 L1 and 68 E7
m Seven anal specimens were unable to be evaluated for HPV
n HR types 16, 31, 33, 53, 59, 45, 56, 18, 66; probable HR-HPV types 26, 35, 39, 51, 52, 58, 68, 69, 70, 73, 82, IS39; LR-HPV types ;6, 11, 40, 42, 54, 61, 72, 81, CP6108; undetermined risk types 55, 62, 64, 67, 71, 83 and 84
p HR types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68/73b
q HR types 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71,72, 73, 81, 82, 83, 84, CP6108, and IS39
r HR types 6, 11, 16, 18, 26, 31, 32, 33, 35, 39, 40, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 68, 69, 70, 73, AE2, Pap 155, Pap 291, 2, 13, 34, 42, 57, 62, 64, 67, 72, W13B.
The majority of publications were cross-sectional. Study cohort size ranged from 40 to 2107 participants. Eleven of the publications were done in the United States, 4 in Europe, and 3 in Central/South America. The vast majority of publications used PCR to test for HPV. Eight publications utilized PCR combined LR and HR HPV for their prevalence data. Two publications used PCR and either HC2 or flow cytometry, and 1 publication used only HC2. Ten publications reported the prevalence of anal HR HPV infection in their study cohorts ranging from 4% to 36%.
The prevalence of anal HR HPV in women with HPV-related pathology of the vulva, vagina, and cervix compared with women with no known HPV-related pathology varied from 23% to 36% compared with 4–22%, respectively. Véo et al reported the prevalence of HPV in the anal canal of the women with CIN III was greater than in the women without CIN III ( P = .014).
Several publications found that detection of cervical HPV was associated with prevalent anal HPV infection. Other risk factors for anal HPV detection among HIV-negative women include a reported history of anal intercourse, the number of lifetime partners, and a history of perianal and/or vulvar condyloma. Hernandez et al (2013) found that age younger than 30 years increased the risk for anal HPV, and Goodman et al found that an age older than 45 years decreased the likelihood of anal HPV.
The data regarding incidence and clearance of anal HR HPV infection were reported from the Reaching for Excellence in Adolescent Care and Health Project (REACH) and Hawaii Cohorts. The REACH cohort (mean age 17 years) reported an incident anal HR HPV infection rate of 5.3 per 100 person-years, whereas the Hawaii cohort (mean age 39 years) reported an incident anal HR HPV infection rate of 19.5 per 1000 person-months. In this Hawaii cohort, the mean duration of anal HR HPV infection was 5 months (compared with cervical HR HPV infections that lasted a mean of 8 months), and the clearance rate of anal HPV was 9.16/100 woman-months.
A longitudinal study of cervical and anal HPV infection (Hawaii cohort) found the risk of anal HPV infection after cervical infection with concordant genotype was 20.5 (95% confidence interval [CI], 16.3–25.7) compared with the risk of a cervical HPV infection after an anal HPV infection with a concordant genotype of 8.8 (95% CI, 6.4–12.2).
Results
Study characteristics
A total of 60 publications were included in the review. Many of the publications were conducted in women with specific risk factors for anal cancer. Of the anal HPV prevalence publications, 10 publications specified that the population included only HIV-positive women.
Among the publications that did not specify HIV infection, 6 publications were conducted in women with a history of abnormal cervical cytology or intraepithelial neoplasia (IN) 1 or greater of the lower genital tract, 1 publication was conducted among women with non-HIV related immune suppression, and 9 publications were conducted in the general female population.
Among the publications evaluating anal cytological findings, 14 publications evaluated study cohorts of HIV-positive women, 12 publications evaluated study cohorts of women with abnormal cervical cytology or IN1+ of the lower genital tract; and 7 publications assessed anal cytology among the general population. Among the anal cancer publications, there were 7 publications among HIV-positive women, 7 publications evaluated women with a history of HPV-related disease of the vulva or cervix, and 9 publications included women from the general population.
Synthesis of results
Anal HPV infection in HIV-positive women
There were 10 publications, utilizing 7 different study cohorts, that specifically evaluated the prevalence and/or incidence of anal HPV infection in HIV-positive women ( Table 1 ). With the exception of 2 papers, all publications reported data on HR HPV.
| Study | Location | Years of study | Study design | Subjects, n | Population (age) a | Methodology for HPV testing | Anal HR HPV prevalence, n (%) | Cervical HR HPV prevalence, n (%) | HPV concordance between the anus and cervix, principal HPV types, and notable findings |
|---|---|---|---|---|---|---|---|---|---|
| Durante et al | United States | 1995–1998 | Baseline data from cohort study | 86 | HIV positive with negative anal cytology (mean, 38) | PCR b | 38 (44) | 27 (31) |
|
| Goncalves et al | Brazil | 1996–1997 | Cross-sectional | 102 | HIV positive | PCR c | 44 (43) | 51 (37) |
|
| Hessol et al 2009 Hessol et al 2013 | United States | 2001–2003 | Point prevalence data within a cohort study | 470 | HIV positive/WIHS | PCR d | 188 (40) | 81 (17) |
|
| Kojic et al | United States | 2004–2006 | Baseline data from cohort study | 120 | HIV positive/SUN (median, 38) | PCR e | 102 (85) | 84 (70) |
|
| Tandon et al Baranoski et al | United States | 2006–2010 | Baseline prevalence and incidence data from cohort study | 100 | HIV positive (mean, 40) | HC2 | 16 (16) f | 24 (24) |
|
| The following publications did not separate the findings based on LR vs HR HPV | |||||||||
| Mullins et al Moscicki et al, 2003 | United States | 1996–2001 | Cohort study | 183 | HIV positive adolescent (REACH) (mean, 17) | PCR (HR and LR) | 59 (32) g | — |
|
| Palefsky et al | United States | 1995–1997 | Point prevalence data within a cohort study | PCR: 223 HC2: 242 | HIV positive/WIHS (mean, 40) | PCR (HR and LR) HC2 (HR and LR) | 170 (76) g 182 (75) g | 106 (53) |
|
a Mean or median age reported when available
b HR types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, and 73
c HR types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82
d HR types 16, 18, 31, 33, 39, 45, 51, 52, 56, 58, 59, and 66
e HR types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 70, 73, 82, and IS39
f HR types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68
The prevalence of anal HR HPV was calculated from baseline, point prevalence, or cross-sectional data from the 7 study cohorts. Two publications calculated incidence of new anal HPV infections from cohort studies. Six of the 7 study cohorts were from the United States.
Most publications used PCR to test for HPV, although the publications differed in HPV types detected ( Table 1 footnotes). Three publications utilizing PCR combined low-risk (LR) and HR HPV for their prevalence data. One publication used both PCR and a HC2 test, and 1 cohort used HC2 only.
Prevalence of HPV in the anus (16–85%) was higher than that of the cervix (17–70%) in the majority of publications. Concordant HPV genotypes between the anus and cervix were found in 9–16% of HIV-positive women (compared with only 2% having concordant HPV genotypes in the HIV-matched cohorts).
The most common prevalent HPV types identified in the anus were 16, 53, 45, 52, 18, and 35 (compared with the concurrent cervical HPV types 16, 52, 53, 58, and 31). Baranoski et al reported the incidence of new anal HR HPV infections was 74 per 1,000 person-years for HIV-positive women over an average follow-up time of 704 days.
Risk factors for prevalent anal HPV included cervical HPV, CD4 less than 200, smoking, and perianal warts. CD4 500 or greater was shown to be significantly protective for anal HPV infection. Of note, reported history of anal intercourse was not associated with anal HPV. Only 1 publication, by Palefsky et al evaluated the effect of most current HIV viral load on the detection of both high-risk and low-risk HPV types by both hybrid capture and PCR and did not find any differences in the detection of HPV using either method between individuals with high HIV viral load compared with low HIV viral load.
Anal HPV infection in predominantly HIV-negative female cohorts
Eighteen publications (representing 13 different study cohorts) reported data on anal HPV prevalence, incidence, or clearance in women not known to be HIV positive ( Table 2 ). The 13 study cohorts varied widely by age, recruitment criteria, population pool, and other inclusion criteria. Six of the cohorts were recruited from women attending colposcopy clinics ; however, the inclusion criteria among these cohorts varied from an abnormal referral cervical cytology, to histological cervical intraepithelial neoplasia (CIN) 3+.
| Study | Location | Years of Study | Study design | Subjects, n | Population (age) a | Methodology for HPV testing | Anal HR HPV prevalence, n (%) b | Cervical HR HPV prevalence, n (%) b | HPV concordance between the anus and cervix, principal HPV types, and notable findings |
|---|---|---|---|---|---|---|---|---|---|
| Park et al | United States | 2006–2007 | Cross-sectional | 92 | IN2+ lower genital tract (including Ca) (HIV positive: n = 1) (mean, 32) | PCR | 33 (36) c | — |
|
| Valari et al | Greece | 2009–2011 | Cross-sectional | 235 | IN1 or greater (including cervical Ca, n =20, and vulva Ca, n =1) (mean, 34) | PCR mRNA (flow) | 72 (31) d 19 (8) e | 91 (39) 60 (26) |
|
| Véo et al | Brazil | — | Cross-sectional | 40 | CIN3 (mean, 33) | HC2 | 9 (23) f | 39 (98) |
|
| 40 | Gynecology clinic (no CIN 3) (mean, 40) | HC2 | 2 (5) f | 3 (8) | |||||
| Goodman et al, 2008 ; Shvetsov | United States | 1998–2003 | Cohort study | 431 | Subset of Hernandez (2005) g (mean, 39) | PCR | 96 (22) h | 143 (33) |
|
| Goodman et al, 2010 | United States | 1998–2008 | Cohort study | 751 | Subset of Hernandez (2005) g (mean, 34) | PCR | — | — |
|
| Hernandez et al, 2013 | United States | 2008–2009 | Cross-sectional | 211 | Women, community (mean, 40) | PCR | 8 (4) i | 11 (5) |
|
| Pierangeli et al | Italy | 2005–2011 | Cross-sectional | 134 | HIV negative, proctology clinic j (mean, 42) | PCR | 18 (13) k | 13/108 (12) |
|
| Hessol et al, 2009 Hessol et al, 2013 | United States | 2001–2003 | Point prevalence within a cohort study | 185 | HIV negative (WIHS) (mean, 29) | PCR | 28 (15) | 13 (1) |
|
| The following publications did not separate the findings based on LR vs HR HPV | |||||||||
| D’Hauwers et al | Belgium | 2007–2008 | Cross-sectional | 96 | Colposcopy clinic (n = 61 ) Gynecology clinic (n = 35 ) (mean, 30) | PCR (HR and LR) | HR and LR 54 (56) b,l | HR and LR 59 (61) b |
|
| Crawford et al | United Kingdom | 2009–2010 | Cross-sectional | 100 | Colposcopy clinic (mean, 34) | PCR (HR and LR) HPV16 HPV31 | 84 (90) b,m,n 52/93 (56) 20/93 (22) | 96 (96) b 55 (53) 24 (24) |
|
| Heraclio et al | Brazil | 2008–2009 | Cross-sectional | 303 | CIN1 or greater (including cervical Ca, n = 26) (HIV positive, n = 8) | PCR (LR and HR) | 255 (84) b,o | — | — |
| Castro et al | Costa Rica | 2004–2005 | Cross-sectional | 2107 | Women, community (22–29 y) | PCR HR and LR PCR HR only | 666 (32) b 464 (22) p | 768 (36) b n/a |
|
| Hernandez et al, 2005 | United States | 1998–2004 | Baseline data from cohort study | 1378 | Women, community | PCR (LR and HR) | 368 (27) b,q | 368 (27) b |
|
| Mullins et al Moscicki et al, 2003 | United States | 1996–2001 | Cohort study | 82 | HIV negative adolescent (REACH) (mean, 17) | PCR (HR and LR) | 11 (13) b | — |
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| Palefsky et al | United States | 1995–1997 | Point prevalence within a cohort study | PCR: 57 HC2: 67 | HIV-negative subset of WIHS (mean, 40) | PCR (HR and LR) HC2 (HR and LR) | 24 (42) b,r HC2: 20 (30) | 12 (24) | — |
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