Infection with high‐risk HPV types among female sex workers in northern Vietnam

Vaccines against two high‐risk human papillomavirus (HPV) types, HPV‐16, and HPV‐18, are in use currently, with high efficacy for preventing infections with these HPV types and consequent cervical cancers. However, circulating HPV types can vary with geography and ethnicity. The aim of this study was to investigate the prevalence of HPV types and the association between HPV types and abnormal cervical cytology among female sex workers in Northern Vietnam. Cervical swabs and plasma samples were collected from 281 female sex workers at two health centers in Hanoi and Hai Phong in 2009. The HPV L1 gene was amplified by PCR using original and modified GP5⁺/6⁺ primers. Amplified PCR products were genotyped by the microarray system GeneSquare (KURABO) and/or clonal sequencing. Of the 281 women, 139 (49.5%) were positive for HPV DNA. Among the HPV‐positive samples, 339 strains and 29 different types were identified. Multiple‐type and high risk‐type HPV infections were found in 85 (61.2%) and 124 (89.2%) women, respectively. The most common genotype was HPV‐52, followed by HPV‐16, HPV‐18, and HPV‐58. Abnormal cervical cytology was detected in 3.2% (9/281) of the women, and all of these samples were positive for HPV‐DNA. Age ≤25 years and infection with human immunodeficiency virus were associated positively with HPV infection among the women while ever smoking was associated negatively. These results show that HPV‐52 is most prevalent among female sex workers in Northern Vietnam, most of whom had normal cervical cytology. This information may be important for designing vaccination strategies in Vietnam. J. Med. Virol. 85:288–294, 2013. © 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.     

The seroprevalence of IgG antibodies to human papillomavirus (HPV) types HPV-16, HPV-18, and HPV-11 capsid-antigens in mothers and their children

Human papillomavirus (HPV) types causing anogenital lesions and cancer are accepted as being sexually transmitted. The methods whereby children acquire these anogenital type HPV infections are unclear. The present study determined the prevalence of anti-HPV-16, HPV-11 and HPV-18 IgG antibodies in mothers and their children in an attempt to identify evidence of HPV transmission from mother to child. HPV virus-like particles (VLP) VLP-16, VLP-11 and VLP-18 were used in enzyme-linked immunosorbent assay to identify IgG antibodies in serum from 100 mothers and their 111 children. Antibodies to VLP-16, VLP-11 and VLP-18 were found in serum from 17%, 21% and 16% of mothers, respectively and seroprevalences were 9%, 11.7% and 9.9%, respectively amongst the children. Of the 111 children, 23 (20.7%) showed antibodies to one or more of the three HPV types tested. Seven of these (30.4%) HPV IgG positive children had the same antibodies to one or more HPV types as their mothers. The prevalence of HPV-11 was similar in children of seropositive compared with seronegative mothers (14% and 11%, respectively). The prevalence of HPV-16 and HPV-18 was higher in children of seropositive mothers compared with seronegative mothers (for HPV-16, 18% and 7%, respectively, P = 0.1, for HPV-18, 19% and 8%, respectively, P = 0.2). None of these differences were statistically significant indicating a lack of correlation between antibodies in mothers and children and no evidence to support vertical or horizontal mother to child transmission of HPV infection. Indications were of multiple sources of HPV infection in the children.     

Viral load and physical status of human papillomavirus (HPV) 18 in cervical samples from female sex workers infected with HPV 18 in Burkina Faso

Viral DNA load and physical status might be predictive of either high‐grade cervical lesions or disease progression among women infected by human papillomavirus (HPV) 16, but these virological markers have rarely been studied in HPV 18 infections. The relationships between HPV 18 DNA load, viral genome physical status and cervical squamous intraepithelial lesions were analyzed among female sex workers infected with HPV18 in Burkina Faso. HPV 18 E2 and E6 genes were quantitated by real‐time PCR. Among 21 women infected with HPV 18, 67% of whom were HIV‐1‐seropositive, 11 (52.4%) had a normal cytology, 8 (38.1%) had low‐grade squamous intraepithelial lesions, and 2 (9.5%) had high‐grade squamous intraepithelial lesions. Total viral load and integrated viral load were higher in women with squamous intraepithelial lesions than in women with normal cytology (P = 0.01 for both parameters). Total viral load and integrated viral load were higher in HIV‐1‐seropositive women than in those who were not infected with HIV (P = 0.01, and P, 0.01, respectively). Total viral load or integrated viral load >1,000 copies/ng of DNA were more frequent in women with squamous intraepithelial lesions than in women with normal cytology (7/10 vs. 1/11; P = 0.007) and in HIV‐1‐seropositive women (8/14 vs. 0/7 in HIV‐uninfected women; P = 0.02). Both HPV 18 DNA and integrated DNA loads might represent markers of cervical lesions. Prospective evaluations are needed to establish the value of these parameters to predict high‐grade lesion or lesion progression. J. Med. Virol. 81:1786–1791, 2009. © 2009 Wiley‐Liss, Inc.     

Oral antibodies to human papillomavirus type 16 in women with cervical neoplasia

This study investigated the relationship between human papillomavirus type 16 (HPV-16) antibodies detected in oral fluid from women with cervical neoplasia, their HPV-16 antibody seroprevalence, and their cervical HPV-16 DNA presence. Cervical HPV-16 DNA was detected by polymerase chain reaction in 43.2% (35/81) of these women. The prevalence of IgG and IgA antibodies to HPV-16 virus-like particles (VLP-16) in oral fluid and was investigated by enzyme-linked immunosorbent assay. Anti-VLP-16 IgA antibodies were detected in oral fluid from 54.3% (44/81) of women with cervical neoplasia, compared with 8% (3/36) in controls (P = 0.000002). Anti-VLP-16 IgG was detected in oral fluid from 43.2.9% (25/72) and 13.3% (4/30; P = 0.029), respectively. Women who were HPV-16 DNA positive at their cervical lesion, displayed an oral fluid anti-VLP-16 IgA prevalence of 60.7% (17/28) and HPV-16 DNA negative women an oral fluid anti-VLP-16 IgA prevalence of 50% (20/40; P = 0.38). Oral fluid anti-VLP-16 IgG prevalence in HPV-16 DNA positive women was 28.6% (8/28) compared with 40% (16/40) in oral fluid from HPV-16 DNA negative women (P = 0.3). Amongst HPV-16 DNA positive women, the anti-VLP-16 IgG seroprevalence was 75% (21/28) and IgA seroprevalence 35.7% (10/28) and for the HPV-16 DNA negative women these values were 60% (24/40) and 32.5% (13/40), respectively. Oral IgA antibody testing proved no more sensitive than serum antibody detection for the determination of HPV infection but could be useful as a non-invasive screening method for women with cervical neoplasia and for estimating the mucosal antibody response to HPV vaccines.     

Undetectable HIV‐1 RNA load with the Cobas TaqMan v1.0 in a patient diagnosed at the time of primary HIV‐1 infection

Diagnosis of primary HIV‐1 infection is challenging due to the presence of a serological window; thus, HIV‐1‐RNA quantitation and/or measurement of p24 antigenemia are recommended in such cases. A patient was diagnosed at the time of primary HIV‐1 infection, he harbored a CFR02_AG subtype virus; quantitation of plasma HIV‐1‐RNA yielded an undetectable result according to one commercial assay, while HIV‐1‐RNA was detectable when measured with three other assays. J. Med. Virol. 82:1816–1818, 2010. © 2010 Wiley‐Liss, Inc.     

High prevalence of HPV 16 in South African women with cancer of the cervix and cervical intraepithelial neoplasia

Despite the high prevalence of cervical cancer and cervical neoplasias in South Africa, few studies have been performed in this region to establish which human papillomavirus (HPV) types are associated with the development of high-grade cervical intraepithelial neoplasia lesions and cervical cancer. To investigate these prevalence rates, punch biopsies were obtained from 56 women with cervical cancer and 141 women with histologically diagnosed cervical intraepithelial neoplasia 2 or 3 lesions. Nested polymerase chain reaction (PCR) using consensus degenerate PCR primers was performed for the detection of HPV DNA and HPV typing was done by restriction fragment length polymorphism. Forty-seven (94%) of the cervical cancer and 114 (88%) of the cervical intraepithelial neoplasia 2/3 biopsies were positive for HPV DNA. The prevalence rates of the HPV types detected in the cervical cancer biopsies were HPV 16 (82%), HPV 18, (10%), HPV 33 (10%), HPV 31 (2%), HPV 58 (2%), HPV 35 (2%), and HPV 59 (2%). The cervical intraepithelial neoplasia lesions contained HPV 16 (56.6%), HPV 33 (14%), HPV 31 (10.9%), HPV X (7%), HPV 52 (3.9), HPV 58 (3.1%), HPV 35 (2.3%), HPV 18 (1.6%), HPV 11 (0.8%). Five of the nine fragments that were not typed by the RFLP, designated HPV-X, were sequenced to give HPV6 (1/5), HPV 26 (2/5), HPV 68 (1/5), and candHPV 87 (1/5). HPV 58 was detected in one cervical cancer biopsy and four biopsies from cervical intraepithelial neoplasia grade 3 lesions and was shown to be a previously described variant [Williamson and Rybicki (1991) J. Med. Virol. 33:165-171]. In addition, a cervical intraepithelial neoplasia grade 2 lesion was shown to harbour HPV type HAN2294 (cand HPV 87). The results of this study indicate that cervical cancer and cervical intraepithelial neoplasia 2/3 are largely associated with HPV 16 infection in this group of South African women and, therefore, an effective HPV 16 based vaccine should prevent the development of cervical cancer in a large proportion of women from this region of South Africa.     

DC contact with HIV‐1‐infected cells leads to high levels of Env‐mediated virion endocytosis coupled with enhanced HIV‐1 Ag presentation

In HIV‐infected patients, DC are likely to interact with both cell‐free HIV and HIV‐infected cells. We were interested in investigating the mechanism of virus transmission occurring upon contact between HIV‐1‐infected cells and DC, as well as the consequences for HIV‐1 Ag‐presenting activity. By comparing mixed co‐cultures with trans‐well cultures, we observed that cell‐to‐cell contact strongly increased HIV‐1 Env‐mediated virion endocytosis in target DC. This endocytosis was independent of HIV‐1 tropism, de novo infection, HIV‐1 Env‐CD4‐dependent fusion, and immature DC activation/maturation. We also found that augmentation of HIV‐1 endocytosis was closely correlated with strong, Env‐dependent HIV‐1 Ag presentation by DC. Our results provide a better understanding of the mechanisms underlying the induction of the anti‐HIV adaptive immune response.     

High level of HIV‐2 false positivity in KwaZulu‐Natal province: A region of South Africa with a very high HIV‐1 subtype C prevalence

Human immunodeficiency virus 2 (HIV‐2) is found predominantly in West Africa. It is not unlikely, however, that HIV‐2 may also be found in South Africa, due to the influx of immigrants into this country. It is important to distinguish between HIV‐1 and HIV‐2 since the clinical courses and treatment responses of these viruses are different. Routine serological methods for diagnosing HIV do not differentiate between HIV‐1 and ‐2 infections, while rapid tests, viral load quantification and PCR are HIV‐type—specific. The objective of this study was to describe the seroprevalence and molecular epidemiology of HIV‐2 in KwaZulu‐Natal, one of the regions with the highest HIV prevalence in the world and home of the two largest harbors in South Africa. HIV‐1 positive samples were screened for antibodies against HIV‐2, using a rapid test. The confirmation of HIV‐2 positive samples was done by PCR. Of the 2,123 samples screened, 319 (15%) were identified as positive by the rapid test. None of these samples were confirmed positive by PCR. To explore this discrepancy in the results, a subset (n = 52) of the rapid HIV‐2 positive samples was subjected to Western blotting. Thirty‐seven (71%) of these were positive, yielding an overall HIV‐2 seroprevalence of 10.6%. Three out of 28 (10.7%) Western blot positive samples were positive by a Pepti‐LAV assay. This discrepancy between serological and molecular confirmation may be attributed to non‐specific or cross‐reacting antibodies. The use of rapid tests and Western blots for HIV‐2 diagnosis in South Africa should be interpreted with caution. J. Med. Virol. 85:2065–2071, 2013. © 2013 The Authors. Journal of Medical Virology published by Wiley Periodicals, Inc.     

Molecular epidemiology of recent HIV‐1 infections in southern Poland

The genetic diversity of human immunodeficiency virus type 1 (HIV‐1) offers an opportunity to track the development of the epidemic across different populations. Viral pol gene fragments from 55 individuals of Polish origin with recent HIV‐1 infection identified in 2008–2010 in four Polish cities were analyzed. Viral sequences were compared with sequences from 100 individuals (reference group) infected before 2004. Viral spread among groups with different HIV transmission categories was compared using a phylogenetic approach. The majority of sequences from individuals with recent infection were subtype B (93%) within which four transmission clusters (18% of samples) were detected. Samples from men infected through sex between men and from persons infected through injecting drugs were broadly separated (P < 0.0001), while samples from individuals infected by heterosexual contacts were dispersed uniformly within phylogenetic tree (P = 0.244) inferred from viral sequences derived from individuals infected recently and the reference group. The percentage of samples from persons infected by heterosexual contacts which clustered with samples from men infected through sex between men was not significantly higher for those with recent infection (47%), compared to the reference group (36%). In conclusion, men infected by sex between men and individuals infected through injecting drugs appear to form separate HIV transmission networks in Poland. The recent spread of HIV‐1 among persons infected with subtype B by heterosexual contacts appears to be linked to both these groups. J. Med. Virol. 84:1857–1868, 2012. © 2012 Wiley Periodicals, Inc.     

p16 and Ki67 expression in normal,dysplastic and neoplastic uterine cervical epithelium and human papillomavirus (HPV) infection

Cellular cycle proteins like the p16^INK4a and the Ki67 proliferation nuclear antigen have been used as oncogenicity cellular markers. The E6 and E7 oncoproteins interact with tumor suppressor genes p53 and pRb, culminating with the p16^INK4a overexpression.     

The human papillomavirus (HPV) vaccine,HPV related diseases and cervical cancer in the post-reproductive years

Prophylactic HPV vaccines have demonstrated high efficacy against a range of HPV related diseases. They have been widely adopted as population health interventions in many jurisdictions and their routine use has been endorsed by the WHO. The development of these vaccines comes after an increased understanding of the natural history and epidemiology of HPV infection and disease in both males and females. Persistent HPV infection with oncogenic types induces malignant transformation in a range of epithelia including the cervix, anogenital regions, the penis and a number of head and neck sites. In relation to HPV disease prevention in the post-reproductive years, most infections occur soon after commencement of sexual activity but new infections do occur throughout the age spectrum. This reduces the likely impact of prophylactic vaccines in this population. The major impact on HPV related disease in this age group will come from advances in screening and early detection of HPV and neoplastic precursors. The most appropriate prevention for any individual man or women in this age group will be an individualised combination of vaccination, screening and early detection depending on the individual's own circumstances.     

Low rate of oral human papillomavirus (HPV) infection in women screened for cervical HPV infection in Southern Italy: A cross‐sectional study of 140 immunocompetent subjects

Even though the natural history of cervical and oral human papillomavirus (HPV) infection has been investigated intensely, the possibility that HPV may infect both sites in the same subject is not well documented. This study investigated the frequency of concurrent oral and cervical HPV infection in southern Italian women, in the light of some selected socio‐behavioral variables. One hundred forty women (mean age: 36 years), with known cervical HPV status, were analyzed for oral HPV. Age, smoking/drinking habits, clinical and socio‐behavioral history were assessed by personal interviews. Oral mucosal cells were collected by oral brushing and HPV DNA was sought by the use of nested PCR amplification followed by direct DNA sequencing and the commercial assay INNOLiPA HPV Genotyping (Innogenetics N.V., Ghent, Belgium). The data were analyzed by using the chi‐square test and a logistic regression (logit) model (P < 0.05 statistically significant). Oral HPV infection was detected in 2/140 (1.4%) cases, being present in 2/76 (2.6%) women with cervical HPV infection and 0/64 uninfected women (P = 0.19). A lack of type‐specific concordance in the two patients with concurrent infection was observed. In the sample of population examined, HPV cervical infection does not seem to predispose to oral transmission, even in the presence of oral–genital sexual habits, thus suggesting the independence of infection at the two mucosal sites. J. Med. Virol. 81:1438–1443, 2009. © 2009 Wiley‐Liss, Inc.