Complete genome sequence of a HPV31 isolate from laryngeal squamous cell carcinoma and biological consequences for p97 promoter activity.

Human papillomavirus type 31, although detected less frequently than HPV types 16 and 18, is associated with head and neck squamous cell carcinomas. Previous studies suggest that polymorphisms in the long control region (LCR) may alter the oncogenic potential of the virus. This study reports the first complete genome of a South African HPV31 isolate from a laryngeal squamous cell carcinoma. Sequence variations relative to the HPV31 prototype sequence were identified. The pBlue-Topo® vector, a reporter gene system was used to investigate the possible influence of these variations on the LCR promoter activity in vitro. Using mutagenesis to create two different fragments, ß-galactosidase assays were used to monitor the effect of nucleotide variations on the p97 promoter. Increased ß-galactosidase expression was observed in mutants when compared to the South African HPV31 LCR isolate. Enhanced transcriptional activity was observed with the mutant that possessed a single nucleotide change within the YY1 transcription factor binding site. In conclusion, sequence variation within the LCR of HPV31 isolates may have a functional effect on viral p97 promoter activity.

Distribution of human papillomavirus genotypes in western China and their association with cervical cancer and precancerous lesions.

The aim of this study was to describe the distribution of human papillomavirus (HPV) genotypes among cervical cancers and pre-cancers in Shaanxi province of western China. A total of 17,341 women who were screened for cervical cancer from January 2014 to December 2016, using HPV genotyping and ThinPrep cytologic test were included. The prevalence and attribution of HPV genotypes were stratified by cervical lesion and age group. Of the subjects, 26.3% were infected with HPV, 28.0% of whom had multiple infections. The crude HPV prevalence increased from atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions (ASCUS/LSIL, 64.3%) to high-grade squamous intraepithelial lesions (HSIL, 79.8%) and to invasive cervical cancer (ICC, 89.7%, P < 0.001). The three most prevalent genotypes were HPV 16 (8.0%), 58 (4.2%), and 52 (4.0%), and HPV 16, 31 and 33 were positively correlated with increased severity of cervical lesions. Additionally, the divalent vaccine genotypes HPV 16 and 18 accounted for 68.2% of ICC cases. Although 78.5% of ICC and 60.3% of HSIL cases were attributed to 9-valent vaccine genotypes, the other genotypes not covered by any vaccine still resulted in increases in coverage, with 1.5% for ICC, 5.3% for HSIL, and 13.5% for ASCUS/LSIL. HPV prevalence in western China was consistent with other regions of China. Early vaccination with 9-valent HPV vaccine is recommended in this locality for females younger than 26 years with no prior infection, while divalent the vaccine is more appropriate for women between 26 and 45 years, considering the efficacy, safety and cost-effectiveness of vaccines.

Prevalence of human papillomavirus in archival head and neck cancer in the eastern Inner Mongolian Autonomous Region, China.

OBJECTIVE: To investigate the prevalence of human papillomavirus (HPV) in archival head and neck cancer (HNC) collected from the Tong-Liao area, which is located in east Inner Mongolia, China. METHODS: The presence of HPV in 54 HNCs and 25 benign biopsies was detected and the sequence variation of the E6 gene in HPV-positive samples was analyzed to determine their lineage/sublineage classification. RESULTS: HPV was detected in only 4 out of 54 HNCs and no benign biopsies were found to be HPV-positive. After further p16INK4a immunostaining, only 3 cases of HNC were positive for both HPV and p16INK4a. Phylogenetic analysis of the isolated E6 gene shows that the HPV 16, HPV 31, and HPV 58 isolated in this study belong to lineage A. CONCLUSIONS: The prevalence of HPV in HNC from this area is very low. The lineage/sublineage classification of the 3 HPV types in HNC in this area is consistent with the previous reported data of HPV lineage distribution in cervical cancer within China.

Synergistically enhanced colorimetric molecular detection using smart cup: a case for instrument-free HPV-associated cancer screening.

Rationale: Early and accurate detection of disease is crucial for its prevention, identification, and treatment. However, most of disease diagnostics is still limited in clinical laboratories due to the need of complicated instruments and professional personnel. Herein, we reported a smartphone-based synergistically enhanced colorimetric method for molecular diagnostics in our point of care (POC) smart cup platform. Methods: A disposable microfluidic chip was developed for colorimetric loop-mediated isothermal amplification (LAMP) detection of multiple HPV DNA in our POC smart cup platform. The colorimetric detection takes advantage of synergistic effect of PPi4- and H+ ions, two byproducts of LAMP reaction. Color signal of LAMP assay was recorded and analyzed by our custom Android app (dubbed "Hue Analyzer"). Results: Our method not only significantly improves colorimetric readout, but also provides a 10-fold increase in detection sensitivity. It has been successfully applied for HPV-associated cancer screening with spiked saliva and clinical swab samples. Conclusion: The proposed POC diagnostic platform is completely compatible with other nucleic acid biomarkers and has great potential for personalized health monitoring and disease prevention.

Human papillomavirus (HPV) persistence and HPV 31 predict the risk of recurrence in high-grade vaginal intraepithelial neoplasia.

OBJECTIVE: High-grade vaginal intraepithelial neoplasia (vaginal HSIL) represents an uncommon entity. Here, we sought to identify predictors for recurrence and risk factor for developing genital cancers after primary treatment for vaginal HSIL. METHODS: Data of consecutive 5104 women who had human papillomavirus (HPV) DNA test were searched for identify women with histological confirmed vaginal HSIL. Disease-free interval and the risk of developing HPV-related gynecological cancers were assessed using Kaplan-Meier and Cox proportional hazard models. RESULTS: Overall, 77 patients were included. After a mean (SD) follow-up of 69.3 (33.0) months, 11 (14%) and 4 (5%) patients experienced vaginal HSIL recurrence and the occurrence of HPV-related gynecological cancers, respectively. Via multivariate analysis factors predicting for vaginal HSIL recurrence were infection from HPV31 at diagnosis (HR: 5.0 (95%CI:1.17, 21.3); p=0.03) and persistence of HPV infection after treatment (HR: 7.0 (95%CI:1.54, 31.6); p=0.01). Additionally, patients who had LASER ablation experienced a trend toward a lower risk of recurrence in comparison to medical treatment (HR: 0.20 (95%CI:0.03, 1.09); p=0.06). Considering the occurrence of HPV-related gynecological cancers, we observed that no factors independently correlated with this risk; while, a trend towards higher risk was observed for women with HIV infection (HR:16.4 (95%CI:0.90, 300.1); p=0.06) and persistence of HPV infection (HR: 13.3 (95%CI:0.76, 230.2); p=0.07). CONCLUSIONS: Patients affected by vaginal HSIL experienced a relatively high risk of recurrence. Persistence of HPV after treatment and pretreatment HPV-31 infection predicts for high-grade vaginal intraepithelial neoplasia recurrence. Further investigations are warranted in order to corroborate our data.

Prevalence of high-risk human papillomavirus infection among women in Shaanxi province of China: A hospital-based investigation.

This study aimed to investigate the characteristics of female high-risk human papillomavirus (HR-HPV) infection in Shaanxi province of China. A total of 14 111 women were enrolled for HPV genotyping test, and a cytology, and/or cervix biopsy were performed in partial women. Of these women, the HPV infection rate was 30.21%, and 26.73% were caused by HR-HPV. The most common HR-HPV genotypes were HPV-16, HPV-58, HPV-52, HPV-18, and HPV-31. The prevalence of HR-HPV among women older than 50 years was significantly higher than the other groups (P < 0.05). The main carcinogenic genotypes were HPV-16, HPV-18, HPV-58, HPV-52, and HPV-31. HPV-16 and HPV-18 combined caused 80.79% of cervical cancer cases. The infection with multiple HR-HPVs was not a risk factor for cervical lesions. In conclusion, HPV infection was common among women in Shaanxi province. Women older than 50 years were a high-risk group for HR-HPV infection and cervical cancer. HPV-16 and HPV-18 were the main carcinogenic genotypes in this region.

HPV genotyping and p16 expression in Xingu Indigenous Park, Brazil.

The association between high-risk human papillomavirus (HPV) genotypes and p16 expression in indigenous women from the Xingu Indigenous Park, Brazil, was unknown. This study evaluated p16 expression in women with a histological diagnosis of cervical intraepithelial neoplasia (CIN) 3 or higher and correlated this expression with HPV genotypes to determine possible discrepancies in the expression of this marker. We evaluated 37 previously collected samples with different HPV genotypes and high-grade lesions diagnosed based on cytology, histology, and colposcopy. Immunohistochemical analysis was performed using paraffin-embedded tissue sections and the CINtec® Histology Kit. p16 protein expression was investigated by immunostaining with an anti-p16 antibody. HPV genotyping was performed by reverse hybridization. The age of the study population ranged from 22-75 years (43.81 ± 15.89 years) and parity ranged from 1-11 (5.92 ± 2.58). Thirteen different HPV genotypes were found using the INNO-LiPA kit. Single and multiple infections by HPV were found with prevalence of single infections (P = 0.029). Comparison between HPV genotype and simple or multiple infections was highly significant; it was observed more HPV 52 followed by HPV 16 in single infections (P < 0.001). p16 expression was predominantly diffuse, which was observed in 91.7% of lesions, whereas 8.3% were focal (P < 0.001). HPV 52, HPV 16 and 31 were the most prevalent HPV types in high-grade CIN in these indigenous women. Diffuse p16 expression in high-grade CIN was not influenced by the viral genotype; however, more studies are necessary to further our understanding of this restricted group.

Impact of partial bivalent HPV vaccination on vaccine-type infection: a population-based analysis.

BACKGROUND: Data on the effectiveness of one dose of HPV vaccine are lacking, particularly in population-based settings. Data from a national HPV immunisation catch-up programme of 14-18-year-old girls were used to assess the effectiveness of<3 doses of the bivalent vaccine on vaccine-type and cross-reactive-type HPV infection. METHODS: Cervical samples from women attending for their first cervical smear, which had been genotyped for HPV as part of a longitudinal HPV surveillance programme were linked to immunisation records to establish the number of vaccine doses (0, 1, 2 and 3) administered. Vaccine effectiveness (VE) adjusted for deprivation and age at first dose, was assessed for prevalent HPV 16/18 and HPV 31/33/45 infection. RESULTS: VE for prevalent HPV 16/18 infection associated with 1, 2 and 3 doses was 48.2% (95% CI 16.8, 68.9), 54.8% (95% CI 30.7, 70.8) and 72.8% (95% CI 62.8, 80.3). Equivalent VE for prevalent HPV 31/33/45 infection was -1.62% (95% CI -85.1, 45.3), 48.3% (95% CI 7.6, 71.8) and 55.2% (95% CI 32.6, 70.2). CONCLUSIONS: Consistent with recent aggregated trial data, we demonstrate the potential effectiveness of even one dose of HPV vaccine on vaccine-type infection. Given that these women were immunised as part of a catch-up campaign, the VE observed in this study is likely to be an underestimate of what will occur in girls vaccinated at younger ages. Further population-based studies which look at the clinical efficacy of one-dose schedules are warranted.

Loop mediated isothermal amplification (LAMP) for the detection and subtyping of human papillomaviruses (HPV) in oropharyngeal squamous cell carcinoma (OPSCC).

BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is a growing problem that presents a significant challenge to Otolaryngologist-Head and Neck Surgeons. Knowledge of HPV status yields critical prognostic information, with potential for treatment selection based on tumour HPV status. The current gold standard of diagnosis, PCR, is expensive, demanding and time consuming. Alternatives such as p16 immunohistochemistry are subjective and potentially inaccurate. Loop-mediated isothermal amplification (LAMP) is a rapid, robust and inexpensive molecular diagnostic technique. OBJECTIVES: Our aim was to verify LAMP as a potential bedside diagnostic assay for subtyping of HPV in OPSCC. STUDY DESIGN: DNA from 72 formalin-fixed paraffin embedded (FFPE) OPSCC patient samples was tested. PCR and LAMP were then performed to specifically identify HPV 16, 18, 31, 33 and 35. RESULTS AND CONCLUSIONS: For these high-risk subtypes, LAMP had an overall sensitivity of 99.4% and specificity of 93.2% relative to PCR. LAMP is a promising technology that can accurately diagnose high-risk HPV infection.

Validation of a DNA methylation HPV triage classifier in a screening sample.

High-risk human papillomavirus (hrHPV) DNA tests have excellent sensitivity for detection of cervical intraepithelial neoplasia 2 or higher (CIN2+). A drawback of hrHPV screening, however, is modest specificity. Therefore, hrHPV-positive women might need triage to reduce adverse events and costs associated with unnecessary colposcopy. We compared the performance of HPV16/18 genotyping with a predefined DNA methylation triage test (S5) based on target regions of the human gene EPB41L3, and viral late gene regions of HPV16, HPV18, HPV31 and HPV33. Assays were run using exfoliated cervical specimens from 710 women attending routine screening, of whom 38 were diagnosed with CIN2+ within a year after triage to colposcopy based on cytology and 341 were hrHPV positive. Sensitivity and specificity of the investigated triage methods were compared by McNemar's test. At the predefined cutoff, S5 showed better sensitivity than HPV16/18 genotyping (74% vs 54%, P = 0.04) in identifying CIN2+ in hrHPV-positive women, and similar specificity (65% vs 71%, P = 0.07). When the S5 cutoff was altered to allow equal sensitivity to that of genotyping, a significantly higher specificity of 91% was reached (P < 0.0001). Thus, a DNA methylation test for the triage of hrHPV-positive women on original screening specimens might be a valid approach with better performance than genotyping.

[THE FIRST EPIDEMIOLOGICAL DATA ABOUT THE HR-HUMAN PAPILLOMA VIRUS TYPES IN SOUTH AND NORTHERN BULGARIA].

The aim of our study were to evaluate the prevalence of HR-HPV infection in women between 15 and 55 years of age in the South and Northern Bulgaria. We have analyzed the HPV status (using DNA-sorb-AM nucleic acid extraction kit) in cervical samples collected during a 3 year period (2010-2012) from 1020 women, aged 15-55 and divided in four age groups, who attended their gynecologists for HPV-DNA cervical test. The rate of the HR-HPV infection was established to be 39.9%. HR-HPV negative were 60.1% of the evaluated subjects. The most commonly isolated genotype in all 407 (100%) infected women was HPV 16 - 190 women (46.7%), followed by HPV 56 - 78 (19.1%), HPV 31- 48 (11.8%) and HPV 33 - 45 (11.1%). To our knowledge, this is the first survey evaluating the prevalence of HR-HPV infection in the South and Northern regions of Bulgarian towns and drawing attention to the unusually high proportion of different HR-HPV.

Potential coverage of circulating HPV types by current and developing vaccines in a group of women in Bosnia and Herzegovina with abnormal Pap smears.

The objectives of this study were to identify human papillomavirus (HPV) genotypes in a group of Bosnian-Herzegovinian women with abnormal cytology and to assess their potential coverage by vaccines. HPVs were identified by multiplex real-time PCR test (HPV High Risk Typing Real-TM; Sacace Biotechnologies, Italy) of 105 women with an abnormal cervical Pap smear and positive high-risk (HR) HPV DNA screening test. The most common genotypes in the study were HPV-16 (32·6%, 48/147), HPV-31 (14·3%, 21/147), HPV-51 (9·5%, 14/147) and HPV-18 (7·5%, 11/147). The overall frequency of HR HPV-16 and/or HPV-18, covered by currently available vaccines [Gardasil® (Merck & Co., USA) and Cervarix®; (GlaxoSmithKline, UK)] was lower than the overall frequency of other HPVs detected in the study (40·1%, 59/174, P = 0·017). Group prevalence of HR HPVs targeted by a nine-valent vaccine in development (code-named V503) was higher than total frequency of other HPVs detected (68·0%, 100/147, P < 0·001). Development of cervical cytological abnormalities was independent of the presence of multiple infections (χ 2 = 0·598, P = 0·741). Compared to other HPVs, dependence of cervical diagnosis and HPV-16, -18 (P = 0·008) and HPV-16, -18, -31 (P = 0·008) infections were observed. Vaccines targeting HR HPV-16, -18 and -31 might be an important tool in the prevention of cervical disease in Bosnia and Herzegovina.

Human papillomavirus infection in 674 Chinese patients with laryngeal squamous cell carcinoma.

OBJECTIVES: Previous reports suggest a strong association between human papillomavirus (HPV) and the etiology of laryngeal squamous cell carcinoma (LSCC). However, clinical data regarding the HPV infection rate among LSCC patients remain largely inconsistent. METHODS: In total, 674 LSCC patients from three major hospitals in Shanghai were enrolled in this study. We determined the patients' HPV infection status using immunohistochemistry and the GenoArray HPV genotyping assay and calculated their long-term survival rate using the Kaplan-Meier method. RESULTS: The total P16-positive rate according to immunostaining results was 7.57% (51/674). None of the P16-negative patients were HPV-positive according to the HPV genotyping test. The rate of HPV infection among patients with LSCC was 4.9% (33/674). HPV infection was more common among nonsmokers (P<0.05), nondrinkers (P<0.05), and patients with supraglottic LSCC (P<0.05). Of the 33 HPV-positive patients, 28 (84.8%) were infected with HPV-16, 2 with HPV-18, 1 with HPV-31, 1 with HPV-33 and 1 with HPV-45. The 3-year overall survival rate and progression-free survival rate were higher in HPV-positive than HPV-negative patients, but the difference was not statistically significant (76.3% vs. 70.7%, P = 0.30 and 65.1% vs. 58.3%, P = 0.37, respectively). CONCLUSION: HPV was not a main causal factor in LSCC carcinogenesis in this Chinese population. HPV infection did not alter patients' overall survival or progression-free survival rates in this study.

Persistent papillomavirus type-31 and type-45 infections predict the progression to squamous intraepithelial lesion.

OBJECTIVE: Human papillomavirus (HPV) has been recognized as the major etiologic agent of cervical squamous cell carcinoma. However, it has been demonstrated that HPV infection is usually a self-limited process and does not lead to significant epithelial lesions or cancer. Recent data indicate that persistent high-risk HPV (HR-HPV) infections have a significantly increased risk of developing incident high-grade cervical intraepithelial neoplasia and cervical cancer. Our aim, therefore, was to assess whether there exist HPV genotypes whose persistence can be considered powerful surrogates of a progressive disease. We retrospectively selected all patients with a negative cytological diagnosis or with atypical squamous cells of undetermined significance, with a positive test for HR-HPV, different from HPV types 16 and 18, and assessed the significance of the risk of progression based on the persistence of the specific HR-HPV. MATERIALS AND METHODS: We retrospectively queried the database of our Colposcopy Clinic for all patients with a negative cytological diagnosis or with atypical squamous cells of undetermined significance and a positive test for HR-HPV, and we calculated the incidence of progression to lesions greater than or equal to low-grade squamous intraepithelial lesions after 6 months, according to the HPV type. RESULTS: A progression rate of 48.27% was found in patients tested positive for HPV-31 (Group 1), 38.46% in patients tested positive for HPV-45 (Group 2), and 5.73% in patients tested positive for HPV types other than HPV-16, HPV-18, HPV-31, and HPV-45 (Group 3). CONCLUSION: Our data demonstrate that the persistence of HPV-31 and HPV-45 is strongly associated with the occurrence of squamous intraepithelial lesion.

Human papillomavirus genotype distribution and E6/E7 oncogene expression in Turkish women with cervical cytological findings.

BACKGROUND: Infection with certain human papillomavirus (HPV) genotypes is the most important risk factor related with cervical cancer. The objective of the present study was to investigate the prevalence of HPV infection, the distribution of HPV genotypes and HPV E6/E7 oncogene mRNA expression in Turkish women with different cervical cytological findings in Mersin province, Southern Turkey. MATERIALS AND METHODS: A total of 476 cytological samples belonging to women with normal and abnormal cervical Pap smears were enrolled in the study. For the detection and genotyping assay, a PCR/direct cycle sequencing approach was used. E6/E7 mRNA expression of HPV-16, 18, 31, 33, and 45 was determined by type-specific real-time NASBA assay (NucliSENS EasyQ(®)HPV v1.1). RESULTS: Of the 476 samples, 106 (22.3%) were found to be positive for HPV DNA by PCR. The presence of HPV was significantly more common (p<0.001) in HSIL (6/8, 75%) when compared with LSIL (6/14, 42.9%), ASC-US (22/74, 29.7%) and normal cytology (72/380, 18.9%). The most prevalent genotypes were, in descending order of frequency, HPV genotype 66 (22.6%), 16 (20.8%), 6 (14.2%), 31 (11.3%), 53 (5.7%), and 83 (4.7%). HPV E6/E7 oncogene mRNA positivity (12/476, 2.5%) was lower than DNA positivity (38/476, 7.9%). CONCLUSIONS: Our data present a wide distribution of HPV genotypes in the analyzed population. HPV genotypes 66, 16, 6, 31, 53 and 83 were the predominant types and most of them were potential carcinogenic types. Because of the differences between HPV E6/E7 mRNA and DNA positivity, further studies are required to test the role of mRNA testing in the triage of women with abnormal cervical cytology or follow up of HPV DNA positive and cytology negative. These epidemiological data will be important to determine the future impact of vaccination on HPV infected women in our region.

Laser capture microdissection shows HPV11 as both a causal and a coincidental infection in cervical cancer specimens with multiple HPV types.

AIMS: To identify, by laser capture microdissection (LCM), the cellular localization of HPV11 when present with carcinogenic HPV in invasive cervical cancer (ICC) specimens, and to relate this to p16(INK) (4a) expression. METHODS AND RESULTS: Three squamous cell ICC specimens showing coinfection with HPV11 and carcinogenic HPV16 or HPV31 were selected from the Institut Català d'Oncologia international survey of anogenital carcinomas, and coinfection was confirmed by SPF10 -DEIA-LiPA25 analysis. In two cases LCM-PCR identified HPV11 in low-grade and high-grade squamous intraepithelial lesions (SILs) adjacent to the ICC, and HPV16 or HPV31 in the ICC. In one case, HPV11 was the only genotype found in the ICC. P16(INK) (4a) expression was diffuse in ICC associated with carcinogenic HPV, but focal in ICC with HPV11. CONCLUSIONS: Our results confirm that a single cervical, cancerous or precancerous lesion is associated with a single HPV type. Detecting low-risk HPV as a coinfection in whole tissue from ICC does not prove a causal association. HPV11 may be found only in an adjacent SIL with carcinogenic HPV in the ICC. It is also found alone in carcinoma. LCM-PCR and differential P16(INK) (4a) expression can clarify the causal role of each type when multiple HPVs are present in whole tissue from carcinomas.

Nested multiplex PCR based detection of human papillomavirus in cervical carcinoma patients of North- East India.

BACKGROUND: Persistent infection of one or more of about 15 high-risk human papillomaviruses (HR-HPVs), most commonly HPV types 16/18, has a significant role in cervical cancer initiation and progression. There are limited data available from north-east India about HPV prevalence though this region has high incidence rates of cervical cancer. The aim of this study was to investigate the HPV genotypes prevalent in cervical cancer patients of north-east India. MATERIALS AND METHODS: We analyzed 107 cervical cancer patient samples. Nested multiplex PCR assays were employed for detection of 13 high risk and 5 low risk HPV types. RESULTS: HPV was confirmed in 105 samples. The presence of 6 'carcinogenic' HPV types, HPV-16 (88%), -18 (15%), -31(4%) ,-45 (3%), -59 (4%), -58(1%), and one non carcinogenic, HPV-6/11 (6%), was recorded. Among various demographic and clinical factors only tumour stage showed a statistically significant association with HPV type infection (P=0.019). CONCLUSIONS: We suggest that the most prevalent genotype is HPV-16 followed by HPV-18 in cervical carcinoma patients of the north-eastern region of India. Advanced tumour stage may be associated with increased possibility of harbouring multiple HPV genotypes.

Sequence variation of human papillomavirus type 31 long control region: phylogenetic and functional implications.

About one-third of human papillomavirus (HPV) types infect the anogenital tract. High-risk genital HPV types (such as HPV 16, 18, 31, 33, and 35) are linked causally to the development of cervical cancer. The long control region (LCR) of the HPV genome regulates the replication and transcription of the viral genome. In this study, the functional significance of nucleotide sequence variation within the LCR of HPV 31 was investigated. The LCR was amplified by polymerase chain reaction (PCR) from 41 HPV 31 positive cervical samples of Hungarian women. A phylogenetic tree constructed from the nucleotide sequences of the LCR variants revealed the presence of three intratypic variant lineages of HPV 31, in accordance with previous results. In order to explore the functional consequences of sequence variation in the LCR of HPV 31, selected LCR variants were cloned into a luciferase reporter vector, transfected into C33-A cells and tested in luciferase reporter assays. Significant differences were found between the transcriptional activities of HPV 31 LCR variants belonging to different variant lineages. As the LCR is governing the transcription of the E6 and E7 oncogenes, the differences in the transcriptional activities of LCR variants may be associated with differences in their oncogenic potential.

Human papillomavirus detection from human immunodeficiency virus-infected Colombian women's paired urine and cervical samples.

Infection, coinfection and type-specific human papillomavirus (HPV) distribution was evaluated in human immunodeficiency virus (HIV)-positive women from paired cervical and urine samples. Paired cervical and urine samples (n = 204) were taken from HIV-positive women for identifying HPV-DNA presence by using polymerase chain reaction (PCR) with three generic primer sets (GP5+/6+, MY09/11 and pU1M/2R). HPV-positive samples were typed for six high-risk HPV (HR-HPV) (HPV-16, -18, -31, -33, -45 and -58) and two low-risk (LR-HPV) (HPV-6/11) types. Agreement between paired sample results and diagnostic performance was evaluated. HPV infection prevalence was 70.6% in cervical and 63.2% in urine samples. HPV-16 was the most prevalent HPV type in both types of sample (66.7% in cervical samples and 62.0% in urine) followed by HPV-31(47.2%) in cervical samples and HPV-58 (35.7%) in urine samples. There was 55.4% coinfection (infection by more than one type of HPV) in cervical samples and 40.2% in urine samples. Abnormal Papanicolau smears were observed in 25.3% of the women, presenting significant association with HPV-DNA being identified in urine samples. There was poor agreement of cervical and urine sample results in generic and type-specific detection of HPV. Urine samples provided the best diagnosis when taking cytological findings as reference. In conclusion including urine samples could be a good strategy for ensuring adherence to screening programs aimed at reducing the impact of cervical cancer, since this sample is easy to obtain and showed good diagnostic performance.

Persistence of newly detected human papillomavirus type 31 infection, stratified by variant lineage.

Variants of human papillomavirus (HPV) type 31 have been shown to be related both to risk of cervical lesions and racial composition of a population. It is largely undetermined whether variants differ in their likelihood of persistence. Study subjects were women who participated in the ASCUS-LSIL Triage Study and who had a newly detected HPV31 infection during a two-year follow-up with six-month intervals. HPV31 isolates were characterized by sequencing and assigned to one of three variant lineages. Loss of the newly detected HPV31 infection was detected in 76 (47.5%) of the 160 women (32/67 with A variants, 16/27 with B variants and 28/66 with C variants). The adjusted hazard ratio associating loss of the infection was 1.2 (95% CI, 0.7-2.1) for women with A variants and 2.1 (95% CI, 1.2-3.5) for women with B variants when compared with those with C variants. Infections with A and C variants were detected in 50 and 41 Caucasian women and in 15 and 23 African-American women, respectively. The likelihood of clearance of the infection was significantly lower in African-American women with C variants than in African-American women with A variants (p = 0.05). There was no difference in the likelihood of clearance between A and C variants among Caucasian women. Our data indicated that infections with B variants were more likely to resolve than those with C variants. The difference in clearance of A vs. C variants in African-Americans, but not in Caucasians, suggests a possibility of the race-related influence in retaining the variant-specific infection.