Prevalence of human papillomaviruses in urine samples of male patients infected with HIV‐1 in Sao Paulo,Brazil

Human papillomavirus is a DNA virus that includes 118 genotypes. HPV16 is responsible for 80% of cervical cancer in women. Men are important reservoirs and major transmitters of HPV to their partners. The aim of this study was to detect HPV DNA and to determine the prevalence of HPV types 6, 11, 16, and 18 in urine samples of men infected with HIV‐1. This study included 223 patients infected with HIV‐1 from the Center of Reference on HIV/AIDS (CRT‐SP) and an outpatient clinic of HIV. Urine samples were collected and after DNA extraction real‐time PCR was performed for detection of HPV DNA. Positive samples were then tested by conventional PCR using type‐specific primers for the four HPV types. A total of 223 men infected with HIV‐1 were tested, 81% of whom were on HAART. Four (5.8%) were positive for HPV6, 18 (26.1%) were positive for HPV11, 22 (31.9%) were positive for HPV16 and five (7.2%) were positive for HPV18 by conventional PCR. Twenty (29%) patients had other HPV types and five patients (1.5%) had multiple types. The mean T CD4+cells count was 517 and 441 cells/mm³ (P = 0.30), in HPV negative and positive men, respectively. The HIV viral load was higher in the HPV negative group than for in the men with HPV (P = 0.0002). A 30.9% prevalence of HPV was found in asymptomatic urine samples of men infected with HIV‐1. This study suggests that urine may be a useful specimen for HPV screening. J. Med. Virol. 81:2007–2011, 2009. © 2009 Wiley‐Liss, Inc.     

Association of cytologic grade of anal “Pap” smears with viral loads of human papillomavirus types 16, 18, and 52 detected in the same specimens from men who have sex with men

BackgroundHuman papilloma virus (HPV) load has been linked to cellular abnormalities of the uterine cervix, and proposed as predictors of HPV persistence and progression of dysplasia to cervical cancer. However, the association of HPV viral load and anal dysplasia and cancer has not been as thoroughly investigated.ObjectivesTo examine the association of the viral loads of high-risk HPV types 16, 18, and 52, with the cytologic severity grading in anal-swab specimens of MSM with and without HIV-1 co-infection.Study designA cross-sectional study recruited 200 MSM in northern Thailand from July 2012 to January 2013. Real-time qPCR amplified portion of the HPV E6E7 gene, as well as the human β-globin gene to validate adequacy of the anal specimens and to normalize interpatient viral-load comparisons. Genotyping by linear-array assay identified and distinguished types 16, 18, and 52.ResultsHPV-16, and -18 viral loads increased with respect to the abnormality of the cytologic diagnoses (p < 0.05 for HPV-16, p < 0.01 for HPV-18). HIV-1 positivity was associated with higher HPV-18 viral load (p = 0.006). HPV-16 viral loads ≥10^2.24 copies per 5000 anal cells, and HPV-18 loads ≥10^3.15, were independently associated with abnormal cytology on logistic regression (p = 0.022, p = 0.041, respectively). Positive predictive values were 85.2% (23/27) and 80.0% (44/55) for the high viral load of a particular HPV-16 and the combined HPV-16, -18 and -52 types, respectively.ConclusionsHigh viral loads of HPV types 16 and 18 appear to be associated with anal cytologic abnormalities. The clinical utility of HPV viral loads to predict risk for anal cancer remains to be determined by a larger prospective cohort with sufficient frequency of high-grade dysplasia.     

Influence of age and CD4+ T cell counts on the prevalence of genital human papillomavirus infection among HIV‐seropositive men who have sex with men in Taiwan

This study aimed to examine the baseline prevalence of genital human papillomavirus (HPV) infection among human immunodeficiency virus (HIV)‐seropositive men who have sex with men in Taiwan and to determine the association of age and CD4+ T cell counts with HPV infection. In 2010, 305 men who have sex with men infected with HIV and 100 HIV‐seronegative men who have sex with men were recruited. Genital swabs were collected and 37 HPV genotypes were detected using linear array HPV genotyping. HPV infection was present in 45.3% of the patients infected with HIV and in 18% of the HIV‐negative subjects (P < 0.001). HPV types 52, 51, and 16 were the most commonly identified oncogenic types. Oncogenic HPV types were identified in 31.2% of the patients infected with HIV and in 13% of the seronegative subjects (P < 0.001). Adjusted odd ratios (ORs) for the detection of any HPV type were 2.9 (95% confidence interval [CI], 1.4–5.9) for men who have sex with men aged 30–34 and 2.1 (95% CI, 1.1–4.3) for those aged >35 compared with that for those aged <25. ORs were 2.8 (95% CI, 1.0–7.4) for a CD4+ T cell count of 200–350 cells/µl and 8.5 (95% CI, 2.9–24.5) for a CD4+ T cell count of <200 cells/µl compared with that for seronegative subjects. In conclusion, this novel HPV study, carried out in Northern Taiwan on men who have sex with men, revealed that age and immune state were associated significantly and independently with HPV infection. J. Med. Virol. 84:1876–1883, 2012. © 2012 Wiley Periodicals, Inc.     

Human papillomavirus (HPV) prevalence and type distribution,and HPV‐associated cytological abnormalities in anal specimens from men infected with HIV who have sex with men

Human papillomavirus (HPV) detection and typing using the PapilloCheck® test and cytological examination were carried out in anal samples collected from 67 men seropositive for human immunodeficiency virus (HIV) who have sex with men. Fifty (74.6%) patients had anal HPV infection, 46 (68.7%) had high‐risk (HR) HPV infection, and 38 (56.7%) had multiple infection involving 2–9 (median, 3) HPV types. The HPV types identified most frequently were HPV 44/55 (19.4%), HPV 53 (19.4%), HPV 16 (16.4%), HPV 39 (16.4%), and HPV 42 (14.9%). Thirty‐two of the 66 interpretable smears (48.5%) revealed cytological abnormalities: 9 (13.4%) atypical cells of undetermined significance, 20 (30.3%) low‐grade intraepithelial lesions, and 3 (4.5%) high‐grade intraepithelial lesions. Cytological abnormalities were associated significantly with HPV detection (P < 0.001), multiple HPV infection (P < 0.001), and increased number of HPV types (P < 0.001). The HPV types associated most frequently with cytological abnormalities were HPV 39 (28.1%), HPV 42 (28.1%), HPV 53 (28.1%), HPV 16 (25.0%), HPV 44/55 (25.0%), and HPV 59 (21.9%). HPV DNA detection as well as cytological abnormalities were associated neither with HIV RNA detection in plasma nor with CD4+ T‐cell count. Differences in age or in time since HIV acquisition were not observed in patients with or without cytological abnormalities. The present study confirms the high prevalence of anal HR‐HPV infection and cytological abnormalities in men infected with HIV who have sex with men. HPV testing and/or cytological analysis may be helpful in selecting the patients to be referred to proctological examination. J. Med. Virol. 82:592–596, 2010. © 2010 Wiley‐Liss, Inc.     

Analytic and Clinical Performance of cobas HPV Testing in Anal Specimens from HIV-Positive Men Who Have Sex with Men

Anal human papillomavirus (HPV) infections are common, and the incidence of anal cancer is high in HIV-infected men who have sex with men (MSM). To evaluate the performance of HPV assays in anal samples, we compared the cobas HPV test (cobas) to the Roche Linear Array HPV genotyping assay (LA) and cytology in HIV-infected MSM. Cytology and cobas and LA HPV testing were conducted for 342 subjects. We calculated agreement between the HPV assays and the clinical performance of HPV testing and HPV genotyping alone and in combination with anal cytology. We observed high agreement between cobas and LA, with cobas more likely than LA to show positive results for HPV16, HPV18, and other carcinogenic types. Specimens testing positive in cobas but not in LA were more likely to be positive for other markers of HPV-related disease compared to those testing negative in both assays, suggesting that at least some of these were true positives for HPV. cobas and LA showed high sensitivities but low specificities for the detection of anal intraepithelial neoplasia grade 2/3 (AIN2/3) in this population (100% sensitivity and 26% specificity for cobas versus 98.4% sensitivity and 28.9% specificity for LA). A combination of anal cytology and HPV genotyping provided the highest accuracy for detecting anal precancer. A higher HPV load was associated with a higher risk of AIN2/3 with HPV16 (P_trend < 0.001), HPV18 (P_trend = 0.07), and other carcinogenic types (P_trend < 0.001). We demonstrate that cobas can be used for HPV detection in anal cytology specimens. Additional tests are necessary to identify men at the highest risk of anal cancer among those infected with high-risk HPV.     

Determinants of the presence of human papillomaviruses in the anal canal of Russian men

Knowledge of determinants of anal human papillomavirus (HPV) infections among men is still limited as most of the studies are focused on high‐risk populations and geographically narrowed. Such knowledge obtained in different populations is essential for better understanding of HPV natural history, transmission dynamics, and its role in the development and prevention of anogenital malignancies in different regions. Here we tested anal canal swab samples from 359 Russian heterosexual (323 human immunodeficiency virus [HIV]‐negative and 27 HIV‐positive, aged 18‐67 years) men attending a sexually transmitted infection clinic 36 HPV types using a proficient Luminex assay. HPV‐positivity in anal samples was common for 332 HIV‐negative heterosexual men for overall HPV (15.7%, n = 52), oncogenic HPV (9.6%, n = 32), nononcogenic HPV (8.1%, n = 27), and multiple HPV infections (4.5%, n = 14). The most common anal HPV types were HPV16 (5.7%), HPV45, and HPV51 (1.8% each), HPV66, and HPV87 (1.8% each). No association was found with the number of lifetime sexual partners, age of participants at the time of the study, or their sexual debut. Although anal HPV positivity was more common among HIV‐positive men, the current study provides additional evidence that anal HPV can be frequently detected in heterosexual HIV‐negative men favoring further studies on transmission routes to discriminate between contamination and true HPV infection.     

Human papillomavirus prevalence and cytopathology correlation in young Ugandan women using a low‐cost liquid‐based pap preparation

Screening for HPV‐driven cervical dysplasia and neoplasia is a significant public health concern in the developing world. The purpose of this study was to use a manual, low‐cost liquid‐based Pap preparation to determine HPV prevalence in HIV‐positive and HIV‐negative young women in Kampala, Uganda and to correlate cervical cytopathology with HPV‐DNA genotype. About 196 post‐partum women aged 18–30 years underwent rapid HIV testing and pelvic examination. Liquid‐based cervical cytology samples were processed using a low‐cost manual technique. A DNA collection device was used to collect specimens for HPV genotyping. HIV and HPV prevalence was 18 and 64%, respectively. Overall, 49% of women were infected with a high‐risk HPV genotype. The most common high‐risk HPV genotypes were 16 (8.2%), 33 (7.7%), 35 (6.6%), 45 (5.1%), and 58 (5.1%). The prevalence of HPV 18 was 3.6%. HIV‐positive women had an HPV prevalence of 86% compared to 59% in HIV‐negative women (P = 0.003). The prevalence of HPV 16/18 did not differ by HIV status. HIV‐positive women were infected with a significantly greater number of HPV genotypes compared to HIV‐negative women. By multivariate analysis, the main risk factor for HPV infection was coinfection with HIV. HIV‐positive women were four times more likely to have abnormal cytology than HIV‐negative women (43% vs. 11.6%, P < 0.001). These data highlight that HIV infection is a strong risk factor for HPV infection and resultant abnormal cervical cytology. Notably, the manual low‐cost liquid‐based Pap preparation is practical in this setting and offers an alternate method for local studies of HPV vaccine efficacy. Diagn. Cytopathol. 2010;38:555–563. 2009 Wiley‐Liss, Inc.     

Circumcision and penile human papillomavirus prevalence in human immunodeficiency virus-infected men: heterosexual and men who have sex with men

Male circumcision is associated with a lower risk of penile human papillomavirus (HPV) infection in human immunodeficiency virus (HIV) uninfected men. Few studies have evaluated the role of male circumcision in penile HPV infection in HIV-infected men. The aim of this cross-sectional study was to examine the association between male circumcision and the prevalence of penile HPV infection among HIV-infected men—both men who have sex with men (MSM) and heterosexual men. Samples from 706 consecutive men included in the CARH-MEN cohort (overall 24% circumcised: 26% of MSM, 18% of heterosexual men) were examined by Multiplex-PCR. In the overall group (all HIV-infected men included), the prevalence of any penile HPV infection was 22% in circumcised men and 27% in uncircumcised men (OR = 1.0, 95% CI 0.6–1.6, adjusted analysis). In the circumcised group the overall prevalence of HPV infection was 22% in MSM and 24% in the heterosexual men, whereas in the uncircumcised group the prevalence was 26% and 28%, respectively. The prevalence of high-risk HPV types tended to be lower in the circumcised MSM (14% vs 21%, OR = 0.6, 95% CI 0.3–1.1, p 0.088), but it was similar in the heterosexual men (18% in circumcised vs 20% in uncircumcised). These results suggest that male circumcision may be associated with a lower prevalence of oncogenic high-risk penile HPV infection in HIV-infected MSM.     

Oral human papillomavirus type-specific infection in HIV-infected men: a prospective cohort study among men who have sex with men and heterosexual men

The natural history of type-specific oral infection of human papillomavirus (HPV) was assessed in a cohort of HIV-infected men (538 men who have sex with men (MSM); 195 heterosexuals). Risk factors associated with oral HPV infections were examined. The overall prevalence of HPV was 16%: HPV-16 was the most prevalent type (3.7% MSM; 7.8% heterosexuals). The prevalence of HPV-16 in heterosexuals was associated with CD4 nadir counts <200 cells/μL (OR_adjusted = 3.0, 95% CI, 1.4–6.3). The overall incidence of HPV was similar between groups (11%), but the incidence of HPV-16 was higher in heterosexuals (OR_adjusted = 3.2, 95% CI, 1.1–9.5). Not only MSM but also HIV-infected heterosexual men are at risk of HPV infection. Regular and careful oral inspection is needed.     

Prevalence and risk factors of HIV and syphilis,and knowledge and risk behaviors related to HIV/AIDS among men who have sex with men in Chongqing,China

High HIV prevalence and incidence burdens have been reported in men who have sex with men (MSM) in Chongqing, China. We aimed to estimate the prevalence of HIV and other sexually transmitted infections (STIs), to appraise the knowledge and risk behaviors related to HIV/AIDS among MSM, and to analyze the possible causes of deviation between behavior and knowledge to make better strategies. We recruited 617 MSM from February to July in 2008 by using a respondent-driven sampling (RDS) method in Chongqing, China. Through the collection of questionnaire-based data and biological testing results from all objects, we launched a cross-sectional survey. STATA/SE was used for data analysis by frequency, ANOVA, rank sum test and logistic regression models. MSM with syphilis (OR=4.16, 95%CI: 2.35-7.33, P<0.0001) were more likely to be HIV infected. Being a company employee (OR=3.64, 95%CI: 1.22-10.08, P<0.0001) and having bought male for sex (OR=3.52, 95%CI: 1.10-11.32, P < 0.034) were associated with a higher probability of syphilis. MSM with younger age, higher education and greater monthly income had a higher mean knowledge score. MSM who had HIV testing had a higher mean knowledge score than those who never had. Students, venues for finding sex partners by Internet and homosexuals in MSM had a higher mean knowledge score compared to other occupations, venues for finding sex partners and sexual orientation. There is an urgent need for delivery of barrier and biomedical interventions with coordinated behavioral and structural strategies to improve the effect of HIV interventions among MSM.     

High‐risk HPV types in lesions of the uterine cervix of female commercial sex workers in the Philippines

In order to prevent cervical cancer, vaccines against human papilloma virus types 16 (HPV‐16) and 18 (HPV‐18) have been implemented worldwide. However, the HPV types that cause cancer can differ according to geographical area and ethnicity. In this new era of the HPV vaccine, it is important to elucidate the prevalent HPV types in each area. Therefore, the prevalence of HPV infection and cervical abnormalities among 369 female commercial sex workers in the Philippines were examined. HPV L1 gene was amplified by polymerase chain reaction (PCR) using modified GP5+/6+ primers, and genotyping was performed by sequencing cloned PCR products. HPV DNA was detected in 211 (57.2%) women, among whom 46 HPV types were identified. HPV‐52 was most common and multiple‐type infection was observed in 44.5%. Among 56 women with abnormal cervical cytology (low‐ and high‐grade squamous intraepithelial lesions and adenocarcinoma in situ), HPV‐52 was most common (23.2%), followed by HPV‐16 (19.6%), ‐58 (10.7%), and ‐67 (10.7%). Only 27% of these women were positive for HPV‐16 and ‐18. Multivariate analysis revealed that HPV‐16, ‐39, ‐52, ‐67, and ‐82 were significantly associated with abnormal cytology. Repeated analysis of HPV‐52 single‐positive samples using the original GP5+/6+ PCR primers produced negative results in 57% of cases, suggesting that the prevalence of HPV‐52 infection may have been underestimated in previous studies, and the current vaccines may not be sufficient for preventing infection and the development of premalignant lesions of the cervix in women in the Philippines. J. Med. Virol. 81:545–551, 2009. © 2009 Wiley‐Liss, Inc.     

A comparative study between conventional and liquid‐based cytology in screening for anal intraepithelial lesions in HIV‐positive patients

Anal intraepithelial neoplasia (AIN) is associated with HPV infection and can be detected by cytological screening. While conventional exfoliative cytology (CC) is a low‐cost and nonaggressive method, liquid‐based cytology (LBC) tends to give clearer readings. Although studies of the efficacy of anal cancer screening methods would be of great importance for groups at high risk for AIN, few such studies have been conducted. The aim of the present study was to assess the concordance of CC and LBC in diagnosing anal pre‐neoplastic lesions, and to compare cytological results with anoscopy, histopathological, and molecular biology findings. Comparative study involving 33 HIV‐positive patients, who underwent anoscopy and biopsy of suspected lesions. Concordance between the two cytology methods was calculated, as were the associations between cytology results and findings from other screening methods. A total of 54.5% of cases were considered AIN‐negative by CC and LBC, and concordance between the two methods was statistically significant (P < 0.05). Anoscopy was negative in 15 of the 18 CC‐ and LBC‐negative cases. CC identified 75% of patients with positive biopsy, while LBC identified 85.71% of these patients. Molecular biology results showed that patients with LSIL tested positive for the highest number of HPV subtypes. The associations between positive biopsy and high grade HPV, HPV 16, and multiple HPV infections were not statistically significant. Conventional and liquid‐based cytology are equally effective in screening for anal preneoplastic lesions. Diagn. Cytopathol. 2014;42:840–845. © 2014 Wiley Periodicals, Inc.     

Prevalence and viral load of oncogenic human papillomavirus types associated with cervical carcinoma in a population of North Italy

A cross‐sectional study was carried out in a population of North Italy to determine the prevalence of eight oncogenic human papillomavirus (HPV) types most commonly found in cervical carcinoma and to study the relationship between HPV DNA loads and severity of disease. A total of 597 cervical samples obtained from patients with pathological findings (n = 472) and from women with normal cytology (n = 125) were analyzed by means of normalized Real‐time PCR assays to quantify HPV‐16, ‐18, ‐31, ‐45, and ‐33 group (including ‐33, ‐52, ‐58, ‐67); the normalization of oncogenic HPV viral load was carried out by quantitation of a single copy gene. The two most common oncogenic HPV types found were 16 and 31 (24.3% and 22.9% of pathological samples, respectively); multiple infections were demonstrated in 22% of pathological samples. Overall, the HPV total viral load was found to increase with increasing severity of associated lesions, although a stronger association was observed only for HPV‐31 and HPV‐16 (γ = 0.49 and 0.41, respectively) as compared to HPV‐18 and ‐33 group (γ = 0.19 and 0.02, respectively). However, we found that high levels of HPV‐31 or 33 group DNA could be prognostic of minor oncogenic risk for high‐grade squamous intraepithelial lesions (H‐SIL) (age adjusted odds ratio [AORs] = 1.57 and 1.26, respectively) than HPV‐16 and HPV‐18 (AORs = 30 and 8, respectively). The AORs also increased with HPV total viral load and reached a maximum of AORs = 15.7. Thus, HPV load is a type‐dependent risk marker for the development of H‐SIL. J. Med. Virol. 81:278–287, 2009. © 2008 Wiley‐Liss, Inc.     

Low rate of virological failure and maintenance of susceptibility to HIV‐1 protease inhibitors with first‐line lopinavir/ritonavir‐based antiretroviral treatment in clinical practice

Protease inhibitor (PI)‐resistant HIV‐1 has hardly ever been detected at failed boosted PI‐based first‐line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first‐line lopinavir/ritonavir (LPV/rtv)‐based therapy with available baseline HIV‐1 RNA load, a viral genotype and follow‐up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV‐1 RNA >500 and >50 copies/ml, respectively, after 6 months of treatment. Cox proportional hazard models detected baseline HIV‐1 RNA (RH 1.79, 95%CI 1.10–2.92 per 1 ? log₁₀ increase, P = 0.02) and resistance to the nucleoside backbone (RH 1.04, 95%CI 1.02–1.06 per 10‐point increase using the Stanford HIVdb algorithm, P < 0.001) as independent predictors of HIV‐1 RNA at >500 copies/ml, but not at the >50 copies/ml cutoff criteria. Higher baseline viral load, older patient age, heterosexual route of infection and use of tenofovir/emtricitabine were predictors of failure at month 3 using the 50‐copy and/or 500‐copy threshold. Resistance to LPV/rtv did not occur or increase in any of the available 36 follow‐up HIV‐1 genotypes. Resistance to the nucleoside backbone (M184V) developed in four cases. Despite the likely differences in patient population and adherence, both the low rate of virological failure and the lack of development of LPV/rtv resistance documented in clinical trials are thus confirmed in clinical practice. J. Med. Virol. 82:1996–2003, 2010. © 2010 Wiley‐Liss, Inc.     

Impact of changes in antigen level on CD38/PD‐1 co‐expression on HIV‐specific CD8 T cells in chronic,untreated HIV‐1 infection

Excessive immune activation is a hallmark of chronic uncontrolled HIV infection. During the past years, growing evidence suggests that immune inhibitory signals also play an important role in progressive disease. However, the relationship between positive and negative immune signals on HIV‐specific CD8 T cells has not been studied in detail so far in chronic HIV‐1 infection. In this study, the expression of markers of positive (CD38) and negative (PD‐1) immune signals on virus‐specific CD8 T cells in chronic, untreated HIV‐1 infection was evaluated using intracellular cytokine staining. Viral escape mutations were assessed by autologous virus sequence analysis and subsequent peptide titration assays. Single‐epitope CD8 T‐cell responses toward Gag, Pol, and Nef were compared in 12 HIV‐1 controllers (viral load <5,000 cp/ml) and 12 HIV‐1 progressors (viral load >50,000 cp/ml) and a highly significant increase of CD38/PD‐1 co‐expression on virus‐specific CD8 T cells in progressors was found (P < 0.0001). The level of CD38/PD‐1 co‐expression was independent of epitope specificity. Longitudinal follow‐up revealed a clear drop in CD38/PD‐1 co‐expression on virus‐specific CD8 T cells after the suppression of antigen following either viral escape mutation or the initiation of HAART (P = 0.004). Antigen persistence with a fluctuating viral load revealed stable levels of CD38/PD‐1 co‐expression whereas significant rises in viral load were accompanied or even preceded by substantial increases in CD38/PD‐1 co‐expression. The CD38/PD‐1 phenotype clearly distinguishes HIV‐specific CD8 T‐cell responses between controllers and progressors. Whether it plays a causative role in disease progression remains debatable. J. Med. Virol. 82:358–370, 2010. © 2010 Wiley‐Liss, Inc.     

Genetic variability and phylogeny of the high‐risk HPV‐31, ‐33, ‐35, ‐52, and ‐58 in central Brazil

More than 100 HPV types have been described, 13 of which are classified as high‐risk due to their association with the development of cervical cancer. The intratype genomic diversity of HPV‐16 and ‐18 has been studied extensively, while little data have been generated for other less common high‐risk types. The present study explores the nucleotide variability and phylogeny of the high‐risk HPV‐31, ‐33, ‐35, ‐52, and ‐58, in samples from Central Brazil. For this purpose, the LCR and the E6 and L1 genes were sequenced. Several variants of these HPV types were detected, some of which have been detected in other parts of the world. Furthermore, new variants of all types examined were characterized in a total of 13 new variants. Based on the E6 and L1 sequences, variants were described comprising conservative and non‐conservative amino acid changes. For phylogenetic tree construction, samples characterized in this study were compared to others described and submitted to GenBank previously. The phylogenetic analysis of HPV‐31, ‐33, ‐35, and ‐58 isolates did not reveal ethnic or geographical clustering as observed previously for HPV‐16 and ‐18. HPV‐35 analysis showed a dichotomic branching characteristic of viral subtypes. Interestingly, four clusters relative to the analysis of HPV‐52 isolates were identified, two of which could be classified as Asian and European branches. The genomic characterization of HPV variants is crucial for understanding the intrinsic geographical relatedness and biological differences of these viruses and contributes further to studies on their infectivity and pathogenicity. J. Med. Virol. 81:685–692, 2009 © 2009 Wiley‐Liss, Inc.     

Persistence of high‐risk human papillomavirus infection in a population‐based cohort of Danish women

Persisting human papillomavirus (HPV) infection is a critical step in cervical carcinogenesis. This study was conducted to determine the type‐specific HPV persistence and risk factors for persistence of high‐risk HPV infections in a large cohort of Danish women. The study was based on a population‐based prospective cohort study of women aged 20–29 years. Participants were interviewed and underwent two gynecological examinations 2 years apart. Women with Hybrid Capture 2 results at enrolment and a follow‐up visit were included in the analysis (n = 7,418). Persistence was defined as positivity for the same high‐risk HPV type at both examinations. Overall, 4.2% of the women had persistent HPV infection, accounting for 26.9% of the initially HPV‐positive women. HPV 16, HPV 58, and HPV 31, all from species group alpha 9, were the most persistent types; however, other high‐risk HPV types that are detected rarely in cancer cases were also likely to persist. The number of high‐risk HPV types and detection of HPV 16 infection at baseline and ever use of oral contraceptives increased the risk for persistence. The risk factor analyses also showed that use of an intrauterine device decreased the risk for persistent high‐risk HPV infection among women with one high‐risk HPV type at baseline. No association was found with viral load or smoking. In conclusion, persistent high‐risk HPV infection, especially HPV 16 persistence, was common among women positive for high‐risk HPV. J. Med. Virol. 82:616–623, 2010. © 2010 Wiley‐Liss, Inc.     

HIV‐1 seroconversion promotes rapid changes in cervical human papillomavirus (HPV) prevalence and HPV‐16 antibodies in female sex workers

The extent to which human immunodeficiency virus (HIV‐1) infection impacts on the ability to mount an effective immune response to HPV is unknown, but is relevant in planning HPV vaccine strategies for HIV‐1 infected individuals. This longitudinal study investigated changes shortly after HIV‐1 seroconversion on cervical HPV types and HPV‐16 antibody responses in serum and at the cervix of female sex workers. Typing of HPV DNA from cervical cells was done prior to HIV‐1 seroconversion and within 1 year and greater than 2 years after HIV‐1 seroconversion. Antibody determinations on serum and cervico‐vaginal rinse samples were by HPV‐16 virus‐like particle‐based, enzyme‐linked immunosorbent assay. Of 104 women tested, 40 (38.4%) became HIV‐1 seropositive (HIV‐positive) during the course of the study. Shortly after HIV‐1 seroconversion a significant increase in multiple (>1) HPV infection (OR 4.0, 95% CI 1.3–11.9) was observed compared with HIV‐1 seronegative (HIV‐negative) women and certain changes in HPV type infection. HIV‐1 seroconversion resulted in a reduced prevalence of serum HPV‐16 IgA and cervico‐vaginal IgA and IgG but an increased prevalence of serum HPV‐16 IgG. All HIV‐positive women had been exposed to HPV‐16 as all displayed serum HPV‐16 IgG. Serum HPV‐16 responses were maintained at a high magnitude in the presence of HPV‐16 infection irrespective of HIV infection, but decreased in the absence of HPV‐16 infection. In conclusion, HIV‐1 seroconversion in sex workers rapidly increased cervical HPV infection and caused a reduced ability to produce cervical HPV‐16 antibodies but a continued ability to generate serum IgG antibodies. J. Med. Virol. 81:203–210, 2009. © 2008 Wiley‐Liss, Inc.