It is largely unknown if anti-HPV serum antibody responses vary by anatomic site of infection in men.
This study assessed type-specific anti-HPV serum antibody prevalence associated with corresponding HPV DNA detection in the external genitalia and the anal canal of 1587 heterosexual men and 199 men who have sex with men (MSM).
We observed that HPV 6 and 16 seroprevalence was higher in the presence of same HPV type infection in the anal canal compared to the presence in the external genitalia only, and among MSM compared to heterosexual men. Seropositivity to HPV 6 was strongly associated with HPV 6 DNA detection in the anal canal but not in the external genitalia alone among both heterosexual men (Adjusted Prevalence Ratio (APR), anal+/genital+ vs. anal-/genital-: 4.2 [95% CI: 11.7-10.5]; anal+/genital- vs. anal-/genital-: 7.9 [95% CI: 3.7-17.0]) and MSM (APR, anal+/genital+ vs. anal-/genital-: 5.6 [95% CI: 2.7-11.9]; anal+/genital- vs. anal-/genital-: 3.2 [95% CI: 2.1-4.9]). Similar associations between seropositivity to HPV 16 and anal HPV 16 DNA detection were only observed in MSM (anal+/genital+ vs. anal-/genital-: 3.1 [95% CI: 2.0-5.0]; anal+/genital- vs. anal-/genital-: 2.2 [95% CI: 1.3-3.5]).
Our data demonstrated that seroprevalence varied by anatomic site of HPV infection, suggesting differences in epithelium type present at these anatomic sites may be relevant.
Our finding is instrumental in advancing our understanding of immune mechanism involved in anatomic site-specific antibody response.
Human Papillomavirus (HPV); heterosexual men; men who have sex with men (MSM); seroprevalence; external genitalia; anal canal
OBJECTIVE: To determine whether patients with genital warts carry human papillomavirus (HPV) DNA on their fingers. METHODS: 14 men and eight women with genital warts had cytobrush samples taken from genital lesions, finger tips, and tips of finger nails. Samples were examined for the presence of HPV DNA by the polymerase chain reaction. RESULTS: HPV DNA was detected in all female genital samples and in 13/14 male genital samples. HPV DNA was detected in the finger brush samples of three women and nine men. The same HPV type was identified in genital and hand samples in one woman and five men. CONCLUSION: This study has identified hand carriage of genital HPV types in patients with genital warts. Although sexual intercourse is considered the usual mode of transmitting genital HPV infection, our findings raise the possibility of transmission by finger-genital contact.
To monitor the impact of human papillomavirus types 16 and 18 vaccine on HPV infection dynamics in the Netherlands, we started an ongoing study in sexually transmitted infection (STI) clinics in 2009. Here, we analyze baseline type-specific HPV DNA and HPV-specific antibody positivity rates.
We enrolled 3569 men and women, 16–24 years of age, from 14 STI clinics, and estimated genital and anal HPV DNA and antibody positivity rates of 7 main carcinogenic HPV types. Generalized estimating equations regression analyses were applied to determine risk factors for, and associations between, type-specific HPV DNA and antibody positivity.
Genital HPV DNA positivity rates were higher in women than in men; anal HPV DNA was especially high in men who have sex with men (MSM). HPV antibody seropositivity rates were also highest in women and MSM. High-risk sexual behavior was predictive of both HPV DNA and antibody positivity. Despite a strong correlation in serological profiles for multiple HPV types, seropositivity was independently associated with homologous HPV DNA detection.
HPV DNA and antibody positivity rates are higher in women and MSM than in heterosexual men, but their association is similar across gender. This suggests a site-specific natural course of infection.
Real-time human papillomavirus (HPV) type-specific multiplex PCR assays were developed to detect HPV DNA in specimens collected for the efficacy determination of the quadrivalent HPV (type 6, 11, 16, and 18) L1 virus-like particle (VLP) vaccine (Gardasil). We evaluated the concordance between type-specific multiplex HPV PCR and the widely used, commercially available Roche Linear Array genotyping PCR assay. Female genital swab specimens were tested for the presence of L1, E6, and E7 sequences of HPV type 6 (HPV6), HPV11, HPV16, HPV18, HPV31, HPV45, HPV52, and HPV58 and E6 and E7 sequences of HPV33, HPV35, HPV39, HPV51, HPV56, and HPV59 in type- and gene-specific real-time multiplex PCR assays. Specimens were also tested for the presence of L1 sequences using two versions of the Roche Linear Array genotyping assay. Measures of concordance of a modified version of the Linear Array and the standard Linear Array PCR assay were evaluated. With specimen DNA extraction using the Qiagen Spin blood kit held as the constant, multiplex PCR assays detect more HPV-positive specimens for the 14 HPV types common to both than either version of the Linear Array HPV genotyping assay. Type-specific agreements between the assays were good, at least 0.838, but were often driven by negative agreement in HPV types with low prevalence, as evidenced by reduced proportions of positive agreement. Overall HPV status agreements ranged from 0.615 for multiplex PCR and standard Linear Array to 0.881 for multiplex PCR and modified Linear Array. An alternate DNA extraction technique, that used by the Qiagen MinElute kit, impacted subsequent HPV detection in both the multiplex PCR and Linear Array assays.
Although human papillomavirus (HPV) infection in heterosexual couples has been sparsely studied, it is relevant to understand disease burden and transmission mechanisms. The present study determined the prevalence and concordance of type-specific HPV infection as well as the determinants of infection in heterosexual couples in a rural area of Mexico.
A cross-sectional study was conducted in 504 clinically healthy heterosexual couples from four municipalities in the State of Mexico, Mexico. HPV testing was performed using biotinylated L1 consensus primers and reverse line blot in cervical samples from women and in genital samples from men. Thirty-seven HPV types were detected, including high-risk oncogenic types and low-risk types. Multivariate logistic regression models were utilized to evaluate factors associated with HPV.
The prevalence of HPV infection was 20.5% in external male genitals and 13.7% in cervical samples. In 504 sexual couples participating in the study, concordance of HPV status was 79%; 34 partners (6.7%) were concurrently infected, and 21 out of 34 partners where both were HPV positive (61.8%) showed concordance for one or more HPV types. The principal risk factor associated with HPV DNA detection in men as well as women was the presence of HPV DNA in the respective regular sexual partner (OR = 5.15, 95%CI 3.01-8.82). In men, having a history of 10 or more sexual partners over their lifetime (OR 2.5, 95%CI 1.3 - 4.8) and having had sexual relations with prostitutes (OR 1.7, 95%CI 1.01 - 2.8) increased the likelihood of detecting HPV DNA.
In heterosexual couples in rural regions in Mexico, the prevalence of HPV infection and type-specific concordance is high. High-risk sexual behaviors are strong determinants of HPV infection in men.
Little is known about the prevalence and seroprevalence of low-risk human papillomavirus (HPV) and the risk factors for HPV infection in Korean women. We determined the prevalence of low-risk HPV among 902 women aged 20-59 yr and the seroprevalence of low-risk HPV subtypes 6 and 11 among 1,094 women aged 9-59 yr in the general population. Genital low-risk HPV DNA was assessed by liquid hybridization and polymerase chain reaction. Antibody titers against HPV 6 and 11 were measured by a multiplexed competitive luminex technique. The prevalence of genital low-risk HPV was 4.9%. It reached its highest peak of 10.3% at 20-29 yr of age and a second peak of 3.2% at 50-59 yr of age. The seroprevalence of HPV 6 or 11 was 9.4%. It reached its highest peak of 12.7% at 25-29 yr of age and a second peak of 12.3% at 50-59 yr of age. In multivariable analysis, the number of lifetime sexual partners and past history of sexually transmitted diseases were associated with the seroprevalence but not prevalence of HPV. It is suggested that younger women should receive prophylactic HPV vaccination before they become sexually active and exposed to HPV in their 20s. This study provides baseline data for developing HPV vaccination programs and monitoring vaccine efficacy in Korea.
Low-Risk Human Papillomavirus; Prevalence; Seroprevalence
The epidemiology of human papillomavirus (HPV) in Tanzania is largely unknown both in risk groups and in the general population.
To determine the cumulative seroprevalence of selected HPV types in order to evaluate exposure to HPV in urban Tanzania.
In a cross‐sectional study, sera of 200 patients of both sexes with genital ulcer disease (GUD) and sera of 60 male blood donors and 60 pregnant women were tested for antibodies to the oncogenic HPV types 16, 18, 31, 33, 35, 51 and 52 using an ELISA based on virus‐like particles (VLP).
The overall seroprevalence of HPV types for all patients with GUD was 83% and 77% for women and men, respectively. For pregnant women and male blood donors, the corresponding percentages were 55% and 15%, respectively. The most common HPV types were 16, 18 and 52. Infection with multiple types was more than 10 and 5 times more frequent than infection with a single type 16 in patients with GUD and in pregnant women, respectively. The seroprevalence to HPV types 16, 18, 51 and 52 was considerably higher in HIV‐positive patients with GUD than in HIV‐negative patients.
Infections with the oncogenic HPV types 16, 18 and 52 are common among patients with GUD and pregnant women in urban Tanzania, emphasising the need for control, treatment and implementation of appropriate HPV vaccine programmes.
Objectives: Genital infection with certain types of human papillomavirus (HPV) is the most important risk factor for cervical cancer. The male sexual partner is supposed to be the vector of the infection. However, the knowledge of risk factors for genital HPV DNA in men is limited. The objective of this paper is to study the risk factors for HPV infection in men and to compare them with those found in women, including the study of whether there are different risk profiles for oncogenic and non-oncogenic HPV types.
Methods: From a sexually transmitted diseases (STD) clinic in Denmark, 216 men were consecutively included. A personal interview was done and material for genital HPV DNA detection was obtained with swabs. HPV DNA was detected by polymerase chain reaction (PCR). Odds ratios (OR) for HPV as well as for oncogenic and non-oncogenic types separately were computed with a 95% confidence interval (CI) by means of unconditional multiple logistic regresssion.
Results: The most important predictors of any HPV were lifetime number of sex partners (OR = 4.3; 95% CI 1.4 to 13.1 for 25–39 v 1–9 partners), young age, and being uncircumcised. The most important risk factor for oncogenic HPV types was lifetime number of partners, whereas number of partners in the past year and ever having genital warts were risk factors for the non-oncogenic HPV types. Young age predicted risk of both oncogenic and non-oncogenic HPV types.
Conclusions: Most risk factors for HPV DNA detection in men resemble those found in women. As in women, the risk factor profile for the oncogenic HPV types was different from that of the non-oncogenic HPV types.
The role of circumcision in male HPV acquisition is not clear.
Male university students (18–20 years of age) were recruited from 2003–2009 and followed tri-annually. Shaft/scrotum, glans, and urine samples were tested for 37 alpha HPV genotypes. Cox proportional hazards methods were used to evaluate the association between circumcision and HPV acquisition. Logistic regression was used to assess whether number of genital sites infected at incident HPV detection or site of incident detection varied by circumcision status.
In 477 men, rates of acquiring clinically-relevant HPV types (high-risk types plus types 6 and 11) did not differ significantly by circumcision status (hazard ratio [HR] for uncircumcised relative to circumcised subjects: 0.9[95%CI:0.7–1.2]). However, compared to circumcised men, uncircumcised men were 10.1 (95%CI:2.9–35.6) times more likely to have the same HPV type detected in all 3 genital specimens than in a single genital specimen and were 2.7 (95%CI:1.6–4.5) times more likely to have an HPV-positive urine or glans specimen at first detection.
While the likelihood of HPV acquisition did not differ by circumcision status, uncircumcised men were more likely than circumcised men to have infections detected at multiple genital sites, which may have implications for HPV transmission.
HPV; human papilloma virus; circumcision; epidemiology; risk factors
The aim of this study was to investigate whether antibody responses against synthetic peptides derived from genital human papillomavirus (HPV) proteins are associated with laboratory-proven genital and anorectal HPV infection. In this study, 158 heterosexual patients (110 women and 48 men) were followed prospectively. At each visit we collected serum samples as well as specimens from several sites in the anogenital area for detection of HPV type 6/11 (HPV-6/11), -16, -18, and -33 DNAs by PCR. Immunoglobulin A (IgA) and IgG responses against disrupted bovine papilloma virions and eight different synthetic peptides derived from HPV-6/11, -16, and -18 were determined for serum samples from the first and the last visits. The subjects attended the Municipal Sexually Transmitted Disease Clinic in Amsterdam, The Netherlands, two to seven times (mean, four times) at approximately 4-month intervals. Women were monitored over a period of 155 person-years, and men were monitored over 65 person-years. The magnitudes of the IgA responses against HPV-16 late protein epitopes L1:13, L1:31, and L2:49 were significantly higher in the sera from the last visit among the currently HPV DNA-positive participants than in HPV DNA-negative persons (P = 0.02). When the persons positive for any HPV type at any time during the follow-up period were compared with those who were negative at all times during the follow-up period, we also found a significant elevation of IgA responses against L1:31 and L2:49 (P = 0.04 and 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Human papillomavirus (HPV) is associated with specific benign and malignant lesions of the epithelial and mucosal surfaces. Of the sexually transmitted types, HPV type 16 (HPV 16) and HPV 18 are commonly associated with severe dysplasia and carcinoma of the uterine cervix. In men, genital HPV infections which have been studied are manifest as external lesions usually involving types other than 16 and 18. The nature of HPV 16 and 18 infections in men has not been explored. Since the most common neoplasias of the male genital tract involve the prostate gland, we assayed benign hyperplastic and cancerous prostate tumors for the presence of HPV DNA, using type-specific primers in polymerase chain reaction amplifications. Normal prostatic tissue obtained at autopsy was included in the survey. Amplified sequences specific for HPV 16 were found in 14 of 15 benign prostatic hyperplasias and in all of four carcinomas tested. In contrast, HPV 18 was identified in only three benign hyperplasias, which also contained HPV 16 DNA. Four of five normal prostates demonstrated no HPV infection; one contained HPV 16 sequences. The presence of these oncogenic HPV types in prostate tissues suggests a reservoir for sexual transmission; a potential role for the virus in the etiology of prostatic neoplasia remains to be demonstrated.
Investigation of HPV infection in men remains important due to its association with genital warts and anorectal cancer, as well as to the role men play in HPV transmission to their female sexual partners. Asymptomatic men (n = 43), whose sexual partners had presented cervical HPV infection, were enrolled in this study. Among the 43 men, 23 had their female partner included and tested for HPV-DNA, totaling 23 couples. HPV-DNA was detected by PCR. Type specific PCR to detect HPV 16, 18, 31, 33, 45 and 6/11 was performed. At least one type of HPV was detected in 86.0% (37/43) of the male patients and more than one HPV type was identified in 39.5% (17/43) of the samples, including high and low risk HPV. HPV-16 proved to be the most prevalent viral type in both male and female samples. Concordance of at least one viral type was observed in 56.5% (13/23) of the couples. Among couples that have shown concordance of viral types, 84.6% (11/13) of the men had the same high risk viral type presented by the female sexual partner. These data suggest that HPV infected men is an important reservoir, contributing to a higher transmission to women and maintenance of infection, and consequently, a higher risk of developing cervical cancer. HPV vaccination in men will protect not only them but will also have implications for their sexual partners.
Human papillomavirus (HPV) type-specific distribution was evaluated in genital samples collected from 654 women from the South of Italy undergoing voluntary screening and correlated with cyto-histological abnormalities. HPV DNA was detected in 45.9% of the samples, 41.7% of which had multiple infection and 89.0% had high-risk HPV infection. The prevalence of HPV infection and the rate of multiple infections decreased with age, suggesting natural selection of HPV types with better fitness. In line with other Italian studies, the most common HPV types were HPV-6 and HPV-16, followed by HPV-51, HPV-31, HPV-53, and HPV-66, in women with both normal and abnormal cytology. Cervical intraepithelial lesions grade 2 or 3 were associated with high-risk HPV-16, HPV-18, HPV-31, and HPV-51 infection. These data indicate that prophylactic HPV vaccination is expected to reduce the burden of HPV-related cervical lesions in this population, but also suggest the potential utility of new vaccines with larger type coverage.
Human papillomavirus (HPV) infection is associated with genital malignancy and specific cutaneous malignancies. We report a case of an HPV-associated concurrent vulval intraepithelial neoplasia and periungual Bowen's disease in a young immunocompetent Afro-Caribbean woman with no known risk factors for either disease. HPV genotyping studies detected multiple α and β papillomaviruses with concordance for HPV-34 [a high-risk (HR) mucosal type], and HPV-21 [an epidermodyslasia verruciformis (EV) type] in both vulval and finger tissue. Although the HR-mucosal viruses detected are likely to have a pathogenic role in vulval intraepithelial neoplasia, this is the first report of concordance for EV HPV types in both genital and nongenital skin premalignancies. This case, in the context of accumulating epidemiological and experimental data in cutaneous SCC, raises the question of whether EV HPV may contribute to vulval malignancy, and further study is merited.
Thirty-nine patients with condylomas (12 women and 27 men) attending a dermatology clinic were tested for genital human papillomavirus (HPV) DNA and for seroprevalence to HPV type 6 (HPV6) L1 virus-like particles. The L1 consensus PCR system (with primers MY09 and MY11) was used to determine the presence and types of HPV in sample specimens. All 37 (100%) patients with sufficient DNA specimens were positive for HPV DNA, and 35 (94%) had HPV6 DNA detected at the wart site. Three patients (8%) had HPV11 detected at the wart site, and one patient had both HPV6 and -11 detected at the wart site. Thirteen additional HPV types were detected among the patients; the most frequent were HPV54 (8%) and HPV58 (8%). Baculovirus-expressed HPV6 L1 virus-like particles were used in enzyme-linked immunosorbent assays to determine seroprevalence among the patients with warts. Seronegativity was defined by a control group of 21 women who were consistently PCR negative for HPV DNA. Seroprevalence was also determined for reference groups that included cytologically normal women who had detectable DNA from either HPV6 or HPV16 and women with HPV16-associated cervical intraepithelial neoplasia. Among the asymptomatic women with HPV6, only 2 of 9 (22%) were seropositive, compared with 12 of 12 (100%) female patients with warts. A similar trend in increased HPV6 seropositivity with increased grade of disease was found with the HPV16 DNA-positive women, whose seroprevalence increased from 1 in 11 (9%) in cytologically normal women to 6 in 15 (40%) among women with cervical intraepithelial neoplasia 1 or 3. However, only 4 of 25 (16%) male patients were seropositive.(ABSTRACT TRUNCATED AT 250 WORDS)
A human papillomavirus type 16 (HPV-16) virus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA) was used to measure serum antibody to capsid proteins in 376 sexually active college women who were also screened for the presence of genital HPVs by PCR and interviewed for demographic and behavioral risk factors for HPV infection. The seroprevalence was 46% in women with HPV-16 DNA in the genital tract. The corresponding values for women who harbored other HPV types or no HPV in the genital tract were 30 and 19%, respectively (HPV-16 group versus no-HPV group; odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5 to 8.9). The antibody response was significantly higher among women with a high viral load than among those with a low viral load (median optical density value, 0.838 versus 0.137, P = 0.009). Comparable levels of seroreactivity were observed among women infected with HPV types distantly or closely related genetically to HPV-16. Seroreactivity was significantly associated with an age of 25 to 30 years (OR, 2.3; 95% CI, 1.2 to 4.4), three or more lifetime sexual partners (OR, 2.9; 95% CI, 1.1 to 10), and history of a sexually transmitted disease other than HPV (OR, 3.1; 95% CI, 1.5 to 6.3). The percent seropositivity increased linearly with number of lifetime sexual partners until reaching a plateau at 35% for women with more than six partners (chi for linear trend, P < 0.001). The low sensitivity of HPV-16 VLP-based ELISA may limit the usefulness of the assay as a diagnostic test for HPV-16 infection. However, the assay appears to have adequate specificity and should be useful as an epidemiological marker of HPV-16 infection and sexual behavior.
OBJECTIVE--To study the prevalence of human papillomavirus (HPV) infection, using several different hybridisation techniques, in men whose female sexual partners had cervical HPV and/or cervical intraepithelial neoplasia (CIN). METHODS--The male genital area was examined colposcopically and areas suspicious of HPV changes were biopsied. Each biopsy was subjected to histological examination and HPV DNA analysis by conventional DNA analysis such as Southern, reverse and dot blot as well as with polymerase chain reaction (PCR). RESULTS--Colposcopic examination of men showed 133 to be normal whilst 82 (38%) had clinical or subclinical lesions. Of 55 colposcopically directed biopsies from the male lesions taken, detection of HPV DNA by hybridisation with conventional techniques and by PCR showed HPV DNA in 29 (53%) and 47 (85%) of biopsies respectively. Overall HPV types 6/11 were the predominant types. In 18 (33%) biopsies positive by PCR, multiple types were found. CONCLUSION--HPV DNA was present in the majority of biopsy specimens taken, with HPV 6/11 being the predominant type. Among methods for HPV DNA detection, PCR was the most sensitive and useful technique.
Human papillomavirus type 16 (HPV-16) is strongly associated with the development of cervical cancer. Studies of model systems with animal papillomaviruses have demonstrated the importance of neutralizing antibodies in preventing papillomavirus-associated disease. The assessment of neutralizing antibody responses against HPV-16, previously hampered by the lack of a viral source, was enabled by the recent propagation of an HPV-16 stock in xenografted severe combined immunodeficiency (SCID) mice. HPV-16 infection of an immortalized human keratinocyte cell line was demonstrated by detection of an HPV-16-specific spliced mRNA amplified by reverse transcriptase PCR. Infection was blocked by preincubation of the virus with antiserum generated against HPV-16 virus-like particles (VLPs) composed of the major capsid protein, L1. To examine potential cross-neutralizing activity among the different genital HPV types, rabbit antisera to L1 VLPs corresponding to HPV-6, -11, -18, -31, -33, -35, -39, and -45 were assayed for the ability to block the HPV-16 infection of cultured cells. Antiserum raised against HPV-33 L1 VLPs was the only heterologous antiserum which inhibited HPV-16 infection. Thus, a neutralization assay for HPV-16 may help to characterize the components required to compose a broadly efficacious genital HPV vaccine.
Little is known about detection of genital human papillomavirus (HPV) types in women’s fingertips. The study objectives were to determine the presence of genital HPV types in fingertip samples and agreement between fingertip and genital samples for detecting HPV.
At tri-annual visits, genital and fingertip samples were collected from female university students and tested for 37 HPV genotypes by PCR-based assay. Type-specific concordance between paired fingertip and genital samples was evaluated using a kappa statistic for percent positive agreement (“kappa +”). Paired samples with type-specific concordant fingertip and genital results were selected for variant characterization.
A total of 357 fingertip samples were collected from 128 women. HPV prevalence in fingertip samples was 14.3%. Although percent positive agreement between fingertips and genitals for detecting type-specific HPV was low (17.8%; kappa+=0.17, 95%CI:0.10–0.25), 60.4% of type-specific HPV detected in the fingertips was detected in a concurrent genital sample. All but one of 28 paired concordant samples were positive for the same type-specific variant in the fingertip and genital sample. Re-detection of HPV types at the subsequent visit was more common in genital samples (73.3%) than in fingertip samples (14.5%) (p<.001).
Detection of genital HPV types in the fingertips was not uncommon. While impossible to distinguish between deposition of DNA from the genitals to the fingertips and true fingertip infection, the rarity of repeat detection in the fingertips suggests that deposition is more common.
Finger-genital transmission is plausible, but unlikely to be a significant source of genital HPV infection.
human papillomavirus; fingertip; genital; women; epidemiology
We developed a liquid bead microarray (LBMA) assay for genotyping genital human papillomaviruses (HPVs) based on the MY09-MY11-HMB01 PCR system and the reverse line blot (RLB) assay probe sequences. Using individual HPV plasmids, we were able to detect as few as 50 copies per reaction. In two separate retrospective studies, the LBMA assay was compared to the RLB assay and to the Hybrid Capture II (hc2) assay. Testing was performed without knowledge of other assay results. In the first study, 614 cervical swab samples (enriched for HPV infection) from 160 young women were tested for HPV DNA, and 360 (74.8%) type-specific HPV infections were detected by both assays, 71 (14.8%) by the LBMA assay only, and 50 (10.4%) by the RLB assay only. Type-specific agreement for the two assays was excellent (99.1%; kappa = 0.85; 95% confidence interval [95% CI], 0.82 to 0.88). Samples with discrepant LBMA and RLB test results tended to have low viral loads by a quantitative type-specific PCR assay. In the second study, cervical swab samples from 452 women (including 54 women with histologically confirmed cervical-intraepithelial neoplasia grade 2 or worse [≥CIN2]) were tested initially by the hc2 and subsequently by the LBMA assay. The estimated sensitivities for ≥CIN2 were similar for the LBMA and hc2 assays (98.4% [95% CI, 95.0 to 100%] and 95.6% [95% CI, 89.2 to 100%], respectively). The percentages of negative results among 398 women without ≥CIN2 were similar for the LBMA and hc2 assays (45% and 50%, respectively). The repeat test reproducibility for 100 samples was 99.1% (kappa = 0.92; 95% CI, 0.90 to 0.95). We conclude that the new LBMA assay will be useful for clinical and epidemiological research.
Background. Data on the natural history of human papillomavirus (HPV)–related genital warts (GWs) in men are sparse. We described the distribution of HPV types in incident GWs and estimated GW incidence and time from type-specific incident HPV infections to GW detection in a multinational cohort of men aged 18–70 years.
Methods. Participants included 2487 men examined for GWs and tested for HPV every 6 months and followed up for a median of 17.9 months. Samples were taken from 112 men with incident GWs to test for HPV DNA by polymerase chain reaction.
Results. Incidence of GWs was 2.35 cases per 1000 person-years, with highest incidence among men aged 18–30 years (3.43 cases per 1000 person-years). HPV 6 (43.8%), HPV 11 (10.7%), and HPV 16 (9.8%) were the genotypes most commonly detected in GWs. The 24-month cumulative incidence of GWs among men with incident HPV 6/11 infections was 14.6% (95% confidence interval [CI], 7.5%–21.1%). Median time to GW detection was 17.1 months (95% CI, 12.4–19.3 months), with shortest time to detection among men with incident infections with HPV 6/11 only (6.2 months; 95% CI, 5.6–24.2 months).
Conclusions. HPV 6/11 plays an important role in GW development, with the highest incidence and shortest time to detection among men with incident HPV 6/11 infection.
Typing of human papillomaviruses (HPV) by DNA hybridization procedures, such as reverse line blot (RLB) assay, is sensitive and well validated. However, the application of these assays to high-throughput analyses is limited. Here, we describe the development of multiplex human papillomavirus genotyping (MPG), a quantitative and sensitive high-throughput procedure for the identification of multiple high- and low-risk genital HPV genotypes in a single reaction. MPG is based on the amplification of HPV DNA by a general primer PCR (GP5+/6+) and the subsequent detection of the products with type-specific oligonucleotide probes coupled to fluorescence-labeled polystyrene beads (Luminex suspension array technology). Up to 100 different HPV types can be detected simultaneously with MPG, and the method is fast and labor saving. We detected all 22 HPV types examined with high specificity and reproducibility (the median interplate coefficient of variation was below 10%). Detection limits for the different HPV types varied between 100 and 800 pg of PCR products. We compared the performance of MPG to an established RLB assay on GP5+/6+-PCR products derived from 94 clinical samples. The evaluation showed an excellent agreement (kappa = 0.922) but also indicated a higher sensitivity of MPG. In conclusion, MPG appears to be highly suitable for large-scale epidemiological studies and vaccination trials as well as for routine diagnostic purposes.
The majority of cervical human papillomavirus (HPV) infections in young women are transient, but whether the clearance differs among different HPV genotypes and the different factors predicting genotype-specific clearance are partly unknown. In the Finnish Family HPV Study, 131 of 252 women (mean age, 25.5 years) cleared their infection during the prospective follow-up of 6 years (median, 62.4 months; range, 1.6 to 94.5 months). Cervical scrapings collected at each visit were tested for 24 low-risk and high-risk (HR) HPV types with multiplex HPV genotyping. Poison regression (panel data) was used to estimate predictors for the clearance of species 7 and 9 HPV genotypes. Of all HPV genotypes detected in these women, multiple-type and HPV type 16 (HPV16) infections showed clearance least frequently (46.1% and 50.5%, respectively). The actuarial and crude mean times to first clearance were variable among different genotypes. The actuarial clearance rate (events/person-time at risk) was highest for HPV16 and multiple-type infections, while HPV66 and -82 had the highest crude clearance rate. Independent predictors increasing type-specific clearance of species 7/9 HPV genotypes were older age (incidence rate ratio [IRR] = 1.1; 95% confidence interval [95% CI], 1.03 to 1.18; P = 0.002) and baseline oral HR HPV DNA-negative status (IRR = 2.94; 95% CI, 1.03 to 8.36; P = 0.042), while a higher number of sexual partners during the follow-up decreased the probability of clearance (IIR = 0.35; 95% CI, 0.15 to 0.83; P = 0.018). To conclude, HPV16 and multiple-type infections showed the lowest clearance among young mothers. Increasing age and negative oral HR HPV DNA status at baseline were associated with increased clearance, whereas a higher number of current sexual partners decreased the probability of species 7/9 HPV genotype clearance.
Characterizing short-term detection patterns of young women’s incident alpha-genus human papillomavirus (HPV) infections may further understanding of HPV transmission.
Between 2000–2007, we followed 18–22 year old female university students with triannual HPV DNA and Papanicolau testing. Using Kaplan-Meier methods, we estimated: duration of detectable, type-specific incident infections; time to re-detection (among infections that became undetectable); and time to cervical lesion development after incident infection. We evaluated risk factors for short-term persistent versus transient infection with logistic regression.
303 incident type-specific infections were detected in 85 sexually active women. Median time to first negative test after incident infection was 9.4 (95%CI:7.8–11.2) months; 90.6% of infections became undetectable within two years. 19.4% of infections that became undetectable were re-detected within one year. Cervical lesions were common, and 60% were positive for multiple HPV types in concurrent cervical swabs. Incident HPV detection in the cervix only (versus the vulva/vagina only or both sites) was associated with short-term transience.
While most incident infections became undetectable within two years, re-detection was not uncommon. Cervical lesions were a common early manifestation of HPV infection.
It remains unclear whether potentially modifiable risk factors can be identified to reduce infection duration (and transmission likelihood).
human papillomavirus; incidence; duration; persistence; women; epidemiology
Genital human papillomavirus (HPV) infection is one of the most commonly diagnosed sexually transmitted infections world-wide. Over the last two decades, research has established a strong causal link between specific types of HPV infection and cancer, particularly cervical, anal, vulvar/vaginal, penile, and oropharyngeal cancer. Limited epidemiological studies of anogenital HPV infection have been conducted in Hispanic populations (including Puerto Rico), and population-based incidence and prevalence estimates of HPV infection among Hispanics are limited. Studies that evaluate knowledge and awareness of HPV among men are also scarce. With the world-wide introduction of two new prophylactic vaccines against high-risk HPVs causing cervical cancer, and the recent FDA approval of the quadrivalent vaccine in preventing genital warts in men, there is an urgency to determine the burden of HPV in Hispanic populations before vaccine programs are implemented on a widespread basis. Knowledge and acceptability of the vaccine prior to implementation of these programs are also necessary to allow a targeted assessment. This review article summarizes existing research on HPV infection and HPV-related morbidities in men, with a particular emphasis on Hispanic men in the United States and Puerto Rico. Three major areas are discussed: (1) genital warts, (2) HPV and related cancers and (3) biobehavioral and psychosocial factors related to HPV infection and vaccination. Specific recommendations for advancing HPV research and knowledge among Hispanic populations also are suggested.
HPV infection; Men; Hispanics; Puerto Rico; Anal cancer; Penile cancer