HPV16, HPV18, and HIV infection may influence cervical cytokine intralesional levels

Infection with oncogenic human papillomavirus (HPV) is considered to be the major risk to cervical cancer. This study analyzed the influence of HPV infection on cytokine intralesional levels in cervical lesion in the presence or not of HIV infection. Cervical biopsies from 42 women were studied. HPV detection and typing were performed using amplified DNA hybridized with sequence-specific primers, and cytokine intralesional levels were detected using ELISA. HPV16+ biopsies exhibited increased IFN-gamma and IL-10 when compared to HPV16- (P = 0.03 and 0.04, respectively). HPV18+ biopsies exhibited decreased TNF-alpha (P = 0.009) and IFN- gamma (P = 0.01) when compared to HPV18-. In accordance to HIV status, HIV-/HPV16+ patients exhibited increased IFN-gamma when compared to those presenting HIV-/HPV16- (P = 0.007). HIV-/HPV18+ patients presented decreased IFN-gamma when compared to HIV-/HPV18- (P = 0.02). These results suggest that the presence of HPV16 infection may influence cervical lesion installation, and irrespective of HIV status, HPV18 infection may be more aggressive than HPV-16.     

Prevalence of human papillomavirus types 6, 11, 16, 18, 31, and 33 in a cohort of Greek women

To study HPV prevalence and HPV types 6, 11, 16, 18, 31, and 33 distribution in cervical smears in a cohort of Greek women. One thousand six hundred thirty-six samples were cytologically evaluated and molecularly analyzed, by PCR based assay. Abnormal cytology was identified in 997 women and 75.4% of them were HPV DNA positive, while 639 had normal cytology and 24.6% were HPV DNA positive. HPV was detected in 62.9% of 256 ASCUS smears, 89.3% of 516 LSIL, 86.7% of 60 HSIL and 47.3% of 165 with cervical carcinoma. Overall, HPV 11 was the most common type (13.4%), followed by 18 (10.3%), 6 (7.2%), 16 (6.4%), 31 (3.4%) and 33 (3.4%). Multiple infections with two (11.3%) or more types, primarily 11 and 18 (4.8%), were also identified. Low-risk types 11 and 6 were common in ASCUS (36.6% and 26.4%, respectively), and high-risk types 16 and 18 in HSIL (42.3% and 30.8%, respectively) and in cancer (51.3% and 41%, respectively). Multiple infections were detected in 2.2% of normal and 31.7% of HSIL. HPV prevalence was 75.4% in abnormal and 24.6% in normal cervical smears. HPV 16 and 18 were the most common types in cancer. Single infection with type 11 and multiple infections with 11 and 18 were more frequent.     

Correlation between viral load,multiplicity of infection,and persistence of HPV16 and HPV18 infection in a Dutch cohort of young women

BackgroundPersistent high-risk human papillomavirus infection precedes the development of cervical cancer. Here we evaluated the contribution of HPV16/18 viral load and the presence of infections with multiple HPV types to persistence and clearance of HPV16/18 infections.MethodsVaginal self-swabs were obtained from young women (16–29 y) with one year interval. HPV genotyping was performed using the highly sensitive SPF10-DEIA-LiPA₂₅ system. HPV16/18 DNA loads were quantified via an adapted, highly sensitive qPCR protocol targeting the L1 gene.ResultsWe identified 227 HPV16 and 111 HPV18 infections with follow-up. For HPV16 132/227 (58%) were persistent and 95/227 cleared. For HPV18 49/111 (44%) infections were persistent and 62/111 cleared. Baseline viral load was significantly higher in persistent infections than in clearing infections for both HPV16 (p = 0.022) and HPV18 (p = 0.013). At baseline, only HPV16 viral load was significantly higher in multiple HPV infections compared with single infections (p = 0.003). In logistic regression analysis HPV16 and HPV18 viral load were found to contribute to persistency with OR = 1.279 (95%CI = 1.074–1.524) and OR = 1.256 (95%CI = 1.028–1.533) per log-unit increase HPV16 and HPV18 viral load respectively. The presence of multiple HPV type infections was not associated with higher persistency.ConclusionHPV16/18 viral load might be used as a marker for persisting infections and is affected by the presence of multiple HPV infections. Evaluation of these parameters at the population level may be of value to assess the presence of persistent or clearing HPV16/18 infections as an early marker, and may provide useful quantitative information in (epidemiological) vaccine monitoring studies.     

HPV16/18和HPV16E6/E7DNA在宫颈癌组织中的表达

目的检测HPV16/18和HPV16E6/E7 DNA在宫颈癌组织中的表达,探讨其在宫颈癌发病中的作用.方法应用PCR和琼脂糖凝胶电泳方法检测46例宫颈癌组织中HPV16/18和HPV16E6/E7DNA.结果 46例宫颈癌中56.5%(26/46)扩增HPV16/18 DNA,其中宫颈鳞癌25例,宫颈腺癌1例.正常对照组20例HPV16/18DNA均为阴性,与宫颈癌组相比差异有显著性(P<0.01).HPV16/18 DNA阳性拷贝对数值为4.32±2.45.HPV16E6,E7DNA分别有53.8%(14/26)、46.2%(12/26)扩增.结论 HPV16/18和HPV16E6/E7 DNA与宫颈癌的发生密切相关,是宫颈癌恶性转化的关键之一,预示着宫颈癌有较强的增殖能力和转移能力.     

Cervical and oral human papillomavirus types in HIV-1 positive and negative women with cervical disease in South Africa

This study tested cervical and oral human papillomavirus (HPV) infection in HIV-1 seropositive (HIV+) and seronegative (HIV-) women to determine any association between infections at both sites and the difference in prevalence of the HPV types infecting these women. Participants were 115 women referred to a colposcopy clinic after diagnosis of abnormal cervical cytology. The women showed low grade cervical intraepithelial neoplasia (CIN1) or high grade disease (CIN2/3) or no CIN based on colposcopy and histology. Typing of HPV in cervical and oral cells was by Roche linear array and included direct sequencing on selected oral samples. Cervical HPV prevalence was 86.5% and 97.1% in HIV- and HIV+ women respectively. With the exception of HPV-45, prominent in HIV+ women, the hierarchy of predominant types were similar in HIV- and HIV+ women. HPV-16 was most prevalent in both HIV+ (41.7%) and HIV- women (38.5%) with CIN2/3. Significantly more HIV+ women had multiple cervical (>1) infections than HIV- women (36.1% vs. 88.2%, P < 0.001) and more oral HPV infections (45.5% and 25% respectively; P = 0.04). The most prevalent oral HPV types were HPV-33, -11, and -72. The majority of women did not have concordant oral and cervical HPV types, reflecting possible independence of infection at the two sites. HIV immune suppression did not impact significantly on the predominant types of cervical HPV infection (except for HPV-45). HIV+ women had more multiple HPV infections and those with severe cervical disease a similar prevalence of HIV-16 but a lower HPV-18 prevalence than HIV- women.     

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.     

High frequency of multiple HPV types in cervical specimens from Danish women

Genital human papillomavirus infection (HPV) is common and usually harmless. However, chronic cervical infection with high‐risk HPV types can cause cell changes that may eventually lead to cancer. To determine the frequency of individual HPV types among mixed infections, we examined the type distribution among cervical specimens from more than 1000 Danish women. We also examined the HPV type distribution and the frequency of single and multiple HPV types for specimens from 113 women who underwent conization and were diagnosed with cervical intraepithelial neoplasia grade II or worse (CIN2+). Using microarray technology, we found that 49% of the HPV‐positive patients were infected with multiple HPV types. Among the CIN2+ diagnosed women, this frequency was 41%. The most frequently found high‐risk HPV type was HPV‐16, which was found in 25% of the HPV‐positive cervical specimens. Among the HPV positive CIN2+ diagnosed women, 48% were HPV‐16 positive. Women younger than 30 years of age had a higher frequency of multiple infections (61%) than women older than 30 years (39%). We conclude that cervical infection with multiple HPV types is common among women in all age groups and among women with or without the diagnosis of CIN2+.     

HIV合并HPV阳性标本中HPV的型别检测

目的探讨深圳地区人类免疫缺陷病毒（HIV）阳性人群中人乳头瘤病毒（HPV）感染分型情况,为HIV阳性人群中HPV感染的防治提供依据。方法运用荧光PCR方法和反向斑点杂交技术对HPV阳性患者进行HPV分型检测。结果在HIV感染者中。利用反向点杂交分型方法对40例HPV阳性标本进行HPV基因分型。其中单型感染有18例（45．0％）,混合感染有19例（47．5％）,共检出16种HPV型别,其中包括11种高危型（16、18、31、33、35、45、52、56、58、68、73型）和5种低危型（6、11、42、44、54型）。在16种型别中,感染率最高的为16型（25．0％）,其次为52型（17．5％）、58型（15．0％）。结论感染HIV人群中生殖器部位HPV的感染率较高,在HIV阳性人群中检出性病相关的高危HPV16／52／58亚型．对HIV阳性人群中HPV感染的防治有重要指导意义。     

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.     

Influence of HIV-1 and/or HIV-2 infection and CD4 count on cervical HPV DNA detection in women from Senegal,West Africa

BackgroundHIV infection is associated with greater risk of precancerous lesions and cervical cancer in women. However, several factors remain unclarified regarding the association between HIV infection and HPV detection, especially among those with HIV type 2 versus type 1 infection and severely immunocompromised persons.ObjectivesTo evaluate HPV overall and type-specific detection among HIV-infected and uninfected women in Senegal.Study designDetection of HPV DNA for 38 genotypes in cervical swabs using PCR-based methods was evaluated in HIV-positive (n = 467) and HIV-negative (n = 2139) women participating in studies in Senegal. Among HIV-1 and/or HIV-2 positive women, CD4 counts were assessed. Adjusted multivariable prevalence ratios (PR) were calculated.ResultsThe prevalence of any HPV DNA and multiple HPV types was greater among HIV-infected individuals (78.2% and 62.3%, respectively) compared with HIV-negative women (27.1% and 11.6%). This trend was also seen for HPV types 16 and 18 (13.1% and 10.9%) compared to HIV-negative women (2.2% and 1.7%). HIV-infected women with CD4 cell counts less than 200 cells/μl had a higher likelihood of any HPV detection (PR_a 1.30; 95% CI 1.07–1.59), multiple HPV types (PR_a 1.52; 95% CI 1.14–2.01), and HPV-16 (PR_a 9.00; 95% CI 1.66–48.67), but not HPV-18 (PR_a 1.20, 95% CI 0.45–3.24) compared to those with CD4 counts 500 cells/μl or above.ConclusionHIV-infected women, especially those most severely immunocompromised, are more likely to harbor HPV. Measures to prevent initial HPV infection and subsequent development of cervical cancer through focused screening efforts should be implemented in these high risk populations.     

Viral load and genomic integration of HPV 16 in cervical samples from HIV-1-infected and uninfected women in Burkina Faso

The relationships between human papillomavirus type 16 (HPV 16) viral load, HPV 16 integration status, human immunodeficiency virus type 1 (HIV-1) status, and cervical cytology were studied among women enrolled in a cohort of female sex workers in Burkina Faso. The study focused on 24 HPV 16-infected women. The HPV 16 viral load in cervical samples was determined by real-time PCR. Integration ratio was estimated as the ratio between E2 and E6 genes DNA copy numbers. Integrated HPV16 viral load was defined as the product of HPV 16 viral load by the integration ratio. High HPV 16 viral load and high integration ratio were more frequent among women with squamous intraepithelial lesions compared with women with normal cytology (33% vs. 11%, and 33% vs. 0%, respectively), and among women with high-grade squamous intraepithelial lesions compared with women without high-grade squamous intraepithelial lesions (50% vs. 17%, and 50% vs. 11%, respectively). High HPV 16 DNA load, but not high integration ratio, was also more frequent among HIV-1-positive women (39% vs. 9%; and 23% vs. 18%, respectively). The absence of statistical significance of these differences might be explained by the small study sample size. High-integrated HPV 16 DNA load was significantly associated with the presence of high-grade squamous intraepithelial lesions (50% vs. 5%, P = 0.03) in univariate and multivariate analysis (adjusted odds-ratio: 19.05; 95% confidence interval (CI), 1.11-328.3, P = 0.03), but not with HIV-1 or other high-risk HPV types (HR-HPV). Integrated HPV 16 DNA load may be considered as a useful marker of high-grade cervical lesions in HPV 16-infected women.     

Detection of antibodies to L1, L2, and E4 proteins of human papillomavirus types 6, 11, and 16 by ELISA using synthetic peptides

Antibodies against eight synthetic peptides spanning different epitopes located on L1, L2, and E4 proteins of human papillomavirus (HPV) types 16, 6, and 11 were examined in sera from 73 women infected by HPV and from 139 healthy controls. Only three of these peptides were reactive. Two located on proteins L2 and E4 of HPV 16 seem type specific since antibodies to these peptides were detected, respectively, in 21% and 15% of the HPV 16 infected patients and in 2.5% and none of women infected by other HPVs. The third peptide located on the L1 protein of HPV 6 bears a common epitope since antibodies to this peptide were detected not only in 85% of women infected by HPV 6 or 11, but also in 82% of women infected by other HPVs, and in 74% and 71% of the control groups (10–12-year-old children and adults, respectively). In conclusion, none of the peptides investigated seems useful to develop ELISAs for serological diagnosis of HPV infection. © 1995 Wiley-Liss, Inc.     

Seroprevalence of human herpesvirus-8 in blood donors from different geographical regions of Argentina, Brazil, and Chile

Human herpesvirus-8 (HHV-8) causes Kaposi's sarcoma (KS) and lymphoproliferative disorders in both HIV-infected and uninfected patients. HHV-8 has a worldwide occurrence but infection rates vary according to a combination of geographic and behavioral risks. The main transmission route seems to be sexual, nevertheless, nasal secretions, saliva, blood, and organ graft have been proposed. HHV-8 was postulated as a new infectious agent for screening in blood donors. The aim of this study was to evaluate the prevalence of antibodies against HHV-8 antigens in blood donors of South America. Serum samples from 2,470 blood donors from Argentina, Brazil, and Chile corresponding to five geographic regions were studied by indirect immunofluorescence assay (IFA). Seroprevalence rate was 3.7% (92/2,470; 95% CI 2.9-4.5) in the entire blood donor population distributed as follows: Argentina, 4.0% (Buenos Aires city, 4.3%; Bahia Blanca, 2.4%; and Córdoba, 4.0%), Campinas (Brazil), 2.8%; and Santiago de Chile, 3.0%. There was no difference (P>0.05) between men and women or age related, except in Brazil where positive cases were 30-49-year-old males. The present study, which includes different geographical areas of multiple countries from South America, has not been done before. The results show similar prevalence rates among the studied zones corresponding to low-prevalence regions. South America is a large sub-continent with a wide spectrum of population and geographical characteristics, thus, more HHV-8 prevalence studies should be necessary to establish possible regional differences.     

HPV16 E6 variants and HLA class II polymorphism among Chinese women with cervical cancer

Infection with human papillomavirus type 16 (HPV16) confers a high risk for the development of cervical cancer. Variants of this virus may interact differentially with host genetic factors, possibly affecting the disease pathogenesis. This study was designed to investigate the association between HPV16 E6 variants and human leukocyte antigen (HLA) polymorphism within a Chinese population. Peripheral blood from HPV16 positive Chinese women with cervical carcinoma, who had previously been tested for HPV16 E6 variants, was used for HLA class II typing. It was found that there was a significant positive association between DQB1*060101 allele and HPV16 As variant-positive cervical cancers (OR, 4.47; Pc=0.0018). A negative relationship was found between DRB1*150101-DQB1*0602 haplotype and decreased risk for HPV16 As variant-positive cervical cancers (OR=0.31; P=0.037). Similar tendency was observed for the haplotype DRB1*070101-DQB1*0201 with HPV16 As variant-positive cervical cancers (OR=0.16, P=0.024). Additionally, as for the HPV16 E6 prototype-positive cervical cancers, a significant positive association was found in DQB1*060101 allele (OR=5.95; P=0.002; Pc=0.036), and similar trends were observed for DQB1*030201 (OR=10.87, P<0.0001; Pc=0.0018), and DPB1*1301(OR=7.40, P=0.002; Pc=0.04). It was found that there was no significant association between DRB1-DQB1 haplotype and HPV16 prototype-positive cervical cancers. These data indicate that host genetic factors, such as HLA polymorphism, may determine the potential oncogenicity of the HPV16 E6 variant. The results suggest that a specific match between E6 variant proteins and HLA class II alleles may contribute to HPV16-related cervical carcinogenesis in a certain Chinese population.