Performance of urine samples compared to cervical samples for detection of precancer lesions among HPV-positive women attending colposcopy clinic in Mexico City.

BACKGROUND: High-risk human papillomavirus (hrHPV) detection in self-collected urine samples (SeCUS) may be a promising alternative for cervical cancer screening because of its greater acceptability, as long as it can offer comparable sensitivity to clinician-collected cervical samples (CCoS) for detecting precancer lesions. OBJECTIVE: To evaluate the performance of the SeCUS compared to that of the CCoS for cervical intraepithelial neoplasia grade 3 (CIN3) detection among hrHPV-positive women receiving colposcopy in Mexico City using different specific extended HPV typing procedures: HPV16/18, HPV16/18/35/39/68 or HPV16/18/35/39/68/31. METHODS: From March 2017 to August 2018, 4,158 female users of the cervical cancer screening program at Tlalpan Sanitary Jurisdiction in Mexico City were invited to participate in the FRIDA-Tlalpan study. All participants provided ≥ 30 mL of SeCUS, and then a CCoS was obtained with Cervex-Brush®, which was used for hrHPV typing. Participants who tested positive for hrHPV in CCoS were referred for colposcopy for diagnostic confirmation, and all SeCUS of these women were also tested for hrHPV typing. RESULTS: In total, 561 hrHPV-positive women were identified by CCoS via colposcopy, and 82.2% of the SeCUS of these women were also hrHPV positive. From both CCoS and SeCUS, 7 cases of CIN3 were detected. Considering HPV16/18 typing, CCoS and SeCUS detected 4 cases of CIN3, but after HPV16/18/35/39/68/31 extension typing, both CCoS and SeCUS detected all 7 of the CIN3 cases among the hrHPV-positive women. CONCLUSIONS: Using extended hrHPV typing based on HPV16/18/35/39/68/31, our results suggest that the performance of SeCUS may be equivalent to that of CCoS for detecting CIN3 lesions. Although our results are inconclusive, they support the hypothesis that SeCUS may be an attractive alternative worthy of further research.

Performance of an affordable urine self-sampling method for human papillomavirus detection in Mexican women.

INTRODUCTION: Urine self-sampling for human papillomavirus (HPV)-based cervical cancer screening is a non-invasive method that offers several logistical advantages and high acceptability, reducing barriers related to low screening coverage. This study developed and evaluated the performance of a low-cost urine self-sampling method for HPV-testing and explored the acceptability and feasibility of potential implementation of this alternative in routine screening. METHODS: A series of sequential laboratory assays examined the impact of several pre-analytical conditions for obtaining DNA from urine and subsequent HPV detection. Initially, we assessed the effect of ethylaminediaminetetraacetic acid (EDTA) as a DNA preservative examining several variables including EDTA concentration, specimen storage temperature, time between urine collection and DNA extraction, and first-morning micturition versus convenience sample collection. We further evaluated the agreement of HPV-testing between urine and clinician-collected cervical samples among 95 women. Finally, we explored the costs of self-sampling supplies as well as the acceptability and feasibility of urine self-sampling among women and healthcare workers. RESULTS: Our results revealed higher DNA concentrations were obtained when using a 40mM EDTA solution, storing specimens at 25°C and extracting DNA within 72 hrs. of urine collection, regardless of using first-morning micturition or a convenience sampling. We observed good agreement (Kappa = 0.72) between urine and clinician-collected cervical samples for HPV detection. Furthermore, urine self-sampling was an affordable method (USD 1.10), well accepted among cervical cancer screening users, healthcare workers, and decision-makers. CONCLUSION: These results suggest urine self-sampling is feasible and appropriate alternative for HPV-testing in HPV-based screening programs in lower-resource contexts.

Clinical and analytical evaluation of the RealTime High Risk HPV assay in Colli-Pee collected first-void urine using the VALHUDES protocol.

OBJECTIVE: Urine self-sampling has gained increasing interest for cervical cancer screening. In contrast to analytical performance, little information is available regarding the clinical accuracy for high-risk Human Papillomavirus (hrHPV) testing on urine. METHODS: VALHUDES is a diagnostic test accuracy study comparing clinical accuracy to detect high-grade cervical precancer (CIN2+) of HPV testing on self-collected compared to clinician-collected samples (NCT03064087). Disease outcome was assessed by colposcopy and histology. The Abbott RealTime High Risk HPV assay performance was evaluated on Colli-Pee collected first-void urine with cervical outcomes as comparator. RESULTS: As no assay cut-off for urine has been clinically validated, we used the predefined cut-off for cervical samples (CN ≤ 32). Using this cut-off, hrHPV testing was similarly sensitive (relative sensitivity 0.95; 95% CI: 0.88-1.01) and specific (relative specificity 1.03; 95% CI: 0.95-1.13) for detection of CIN2+ compared to testing cervical samples. In the subgroup of women of 30 years and older, similar relative sensitivity (0.97; 95% CI: 0.89-1.05) and specificity (1.02; 95% CI: 0.93-1.12) was found. Additionally, an exploratory cut-off (CN ≤ 33.86) was defined which further improved sensitivity and analytical test performance. CONCLUSION: HrHPV-DNA based PCR testing on home-collected first-void urine has similar accuracy for detecting CIN2+ compared to cervical samples taken by a clinician.

Urine miRNA signature as a potential non-invasive diagnostic and prognostic biomarker in cervical cancer.

MicroRNAs as cancer biomarkers in serum, plasma, and other body fluids are often used but analysis of miRNA in urine is limited. We investigated the expression of selected miRNAs in the paired urine, serum, cervical scrape, and tumor tissue specimens from the women with cervical precancer and cancer with a view to identify if urine miRNAs could be used as reliable non-invasive biomarkers for an early diagnosis and prognosis of cervical cancer. Expression of three oncomiRs (miR-21, miR-199a, and miR-155-5p) and three tumor suppressors (miR-34a, miR-145, and miR-218) as selected by database search in cervical pre-cancer, cancer, and normal controls including cervical cancer cell lines were analyzed using qRT-PCR. The expression of miRNAs was correlated with various clinicopathological parameters, including HPV infection and survival outcome. We observed a significant overexpression of the oncomiRs and the downregulation of tumor suppressor miRNAs. A combination of miR-145-5p, miR-218-5p, and miR-34a-5p in urine yielded 100% sensitivity and 92.8% specificity in distinguishing precancer and cancer patients from healthy controls and it well correlates with those of serum and tumor tissues. The expression of miR-34a-5p and miR-218-5p were found to be independent prognostic factors for the overall survival of cervical cancer patients. We conclude that the evaluation of the above specific miRNA expression in non-invasive urine samples may serve as a reliable biomarker for early detection and prognosis of cervical cancer.

Urine collection in cervical cancer screening - analytical comparison of two HPV DNA assays.

BACKGROUND: To reach non-participants, reluctant to undergo clinician-based cervical cancer screening and vaginal self-sampling, urine collection for high-risk human papillomavirus detection (hrHPV) may be valuable. Using two hrHPV DNA assays, we evaluated the concordance of hrHPV positivity in urine samples in comparison with vaginal self-samples and cervical cytology samples taken by the general practitioner (GP). We also studied women's acceptance of urine collection and preferences towards the different sampling procedures. METHODS: One hundred fifty paired self-collected urine and vaginal samples and GP-collected cervical cytology samples were obtained from 30 to 59-year-old women diagnosed with ASC-US within the Danish cervical cancer screening program. After undergoing cervical cytology at the GP, the women collected first-void urine and vaginal samples at home and completed a questionnaire. Each sample was hrHPV DNA tested by the GENOMICA CLART® and COBAS® 4800 assays. Concordance in hrHPV detection between sample types was determined using Kappa (k) statistics. Sensitivity and specificity of hrHPV detection in urine was calculated using cervical sampling as reference. RESULTS: With the COBAS assay, urine showed good concordance to the vaginal (k = 0.66) self-samples and cervical samples (k = 0.66) for hrHPV detection. The corresponding concordance was moderate (k = 0.59 and k = 0.47) using CLART. Compared to cervical sampling, urinary hrHPV detection had a sensitivity of 63.9% and a specificity of 96.5% using COBAS; compared with 51.6 and 92.4% for CLART. Invalid hrHPV test rates were 1.8% for COBAS and 26.9% for CLART. Urine collection was well-accepted and 42.3% of the women ranked it as the most preferred future screening procedure. CONCLUSIONS: Urine collection provides a well-accepted screening option. With COBAS, higher concordance between urine and vaginal self-sampling and cervical sampling for hrHPV detection was found compared to CLART. Urinary hrHPV detection with COBAS is feasible, but its accuracy may need to be improved before urine collection at home can be offered to non-participants reluctant to both cervical sampling and vaginal self-sampling.

Methylation analysis in urine fractions for optimal CIN3 and cervical cancer detection.

INTRODUCTION: Urine sampling is an interesting solution for CIN3 and cervical cancer detection. Urine can be separated in different fractions: full void urine, urine sediment and urine supernatant. We aimed to determine which urine fraction is most competent for CIN3 and cervical cancer detection by methylation analysis. METHODS: Urine samples (27 controls, 30 CIN3 and 17 cervical cancer) were processed into 3 fractions and tested for 5 methylation markers (ASCL1, GHSR, LHX8, SST, ZIC1). We determined Spearman correlation coefficients between fractions, compared methylation levels and calculated AUCs for CIN3 and cancer detection. RESULTS: In general strong correlations (r > 0.60) were found between urine fractions. Methylation levels increased significantly with severity of underlying disease in all urine fractions. CIN3 and controls differed significantly for 2 markers in full void urine, 4 markers in urine sediment and 1 marker in urine supernatant, with AUCs of 0.55-0.79. Comparison of cancer to controls was highly significant for all markers in all fractions, yielding AUCs of 0.87-0.99. CONCLUSION: Methylation analysis performs excellent in all urine fractions for cervical cancer detection. Our results indicate the potential of CIN3 detection by urinary methylation analysis, and demonstrate that urine sediment performs best to detect CIN3.

Assessment of clinical performance of an ultrasensitive nanowire assay for detecting human papillomavirus DNA in urine.

OBJECTIVE: To evaluate whether HPV DNA in urine has potential advantages as an alternative biomarker for HPV-based cervical cancer screening. METHODS: Among patients with Cobas HPV test results, a total of 67 HPV-positive (n = 42) and -negative (n = 25) women who agreed to participate in this study were willing to provide paired cervical and urine samples, and we observed concordance between sample types from each patient in identifying HPV genotypes using the nanowire assay. RESULTS: We detected high-risk strains of HPV DNA in unprocessed urine specimens using polyethyleneimine-conjugated nanowires (PEI-NWs). Concordance for high-risk HPV (hrHPV) between paired urine and cervical samples was 90.4% (κ = 0.90; 95% CI: 0.80-100.00). The virological sensitivity and specificity for detection of HPV DNA from a small urine sample (200 µL) were 81.3% (κ = 0.83; 95% CI: 62.1-100.0) and 98.0% (κ = 0.83; 95% CI: 94.2-100.0) for HPV16 group, 100.0% (κ = 0.65; 95% CI: 100.0-100.0) and 95.3% (κ = 0.65; 95% CI: 90.1-100.0) for HPV18 group, and 96.4% (κ = 0.97; 95% CI: 89.6-100.0) and 100.0% (κ = 0.97; 95% CI: 100.0-100.0) for other hrHPV group, respectively. CONCLUSIONS: The nanowire assay demonstrated excellent ability to identify HPV DNA from urine specimens. We observed an excellent agreement in the detection of high-risk HPV between paired urine and cervical samples, even with small urine sample volume.

Cervical cancer detection by DNA methylation analysis in urine.

Urine samples provide a potential alternative to physician-taken or self-collected cervical samples for cervical screening. Screening by primary hrHPV testing requires additional risk assessment (so-called triage) of hrHPV-positive women. Molecular markers, such as DNA methylation, have proven most valuable for triage when applied to cervical specimens. This study was set out to compare hrHPV and DNA methylation results in paired urine and cervical scrapes, and to evaluate the feasibility of DNA methylation analysis in urine to detect cervical cancer. Urine samples (n = 41; native and sediment) and paired cervical scrapes (n = 38) from cervical cancer patients, and urine from 44 female controls, were tested for hrHPV and 6 methylation markers. Results on native urine and sediment were highly comparable. A strong agreement was found between hrHPV testing on urine and scrapes (kappa = 0.79). Also, methylation levels in urine were moderately to strongly correlated to those detected in scrapes (r = 0.508-0.717). All markers were significantly increased in urine from cervical cancer patients compared to controls and showed a good discriminatory power for cervical cancer (AUC = 0.744-0.887). Our results show a good agreement of urine-based molecular analysis with reference cervical samples, and suggest that urine-based DNA methylation testing may provide a promising strategy for cervical cancer detection.

Discriminating high-risk cervical Human Papilloma Virus infections with urinary biomarkers via non-targeted GC-MS-based metabolomics.

Genital human papillomavirus (HPV) is the world's most commonly diagnosed sexually transmitted infection, and high-risk HPV types are strongly linked to cervical dysplasia and carcinoma. Puerto Ricans are among the US citizens with higher HPV prevalence and lower screening rates and access to treatment. This bleak statistic was as a motivation to detect biomarkers for early diagnosis of HPV in this population. We collected both urine and cervical swabs from 43 patients attending San Juan Clinics. Cervical swabs were used for genomic DNA extractions and HPV genotyping with the HPV SPF10-LiPA25 kit, and gas chromatography-mass spectrometry (GC-MS) was employed on the urine-derived products for metabolomics analyses. We aimed at discriminating between patients with different HPV categories: HPV negative (HPV-), HPV positive with simultaneous low and high-risk infections (HPV+B) and HPV positive exclusively high-risk (HPV+H). We found that the metabolome of HPV+B is closer to HPV- than to HPV+H supporting evidence that suggests HPV co-infections may be antagonistic due to viral interference leading to a lower propensity for cervical cancer development. In contrast, metabolites of patients with HPV+H were significantly different from those that were HPV-. We identified three urinary metabolites 5-Oxoprolinate, Erythronic acid and N-Acetylaspartic acid that discriminate HPV+H cases from negative controls. These metabolites are known to be involved in a variety of biochemical processes related to energy and metabolism and may likely be biomarkers for HPV high-risk cervical infection. However, further validation should follow using a larger patient cohort and diverse populations to confirm our finding.

A prospective pilot evaluation of vaginal and urine self-sampling for the Roche cobas 4800 HPV test for cervical cancer screening.

This pilot study sought to evaluate the feasibility of utilizing vaginal self-swabs and urine samples for HPV-based cervical cancer screening in 700 women who had undergone conventional Pap smear screening via the national cervical cancer program in Korea. The cobas 4800 HPV test was utilized to detect HPV in the self-samples. Pap smear results revealed three cases of atypical squamous cells of undetermined significance, 649 cases of negative for an intraepithelial lesion or malignancy, and 48 non-specific inflammatory findings. High-risk HPV was detected in 6.7% of urine samples and 9.6% of vaginal self-swab samples. The overall agreement for HPV 16/18 between urine and vaginal self-swab samples was 99.1% (95%CI 98.1% to 99.6%). Colposcopic biopsy revealed one cervical intraepithelial neoplasia (CIN) 3 lesion, 12 CIN1 lesions, and 23 normal or chronic cervicitis lesions. In conclusion, urine and vaginal self-swab sampling was feasible and deemed a potential alternative for HPV detection in women who hesitate to participate in cervical cancer screening programs. Meanwhile, due to overall lower rates of abnormal cytology and sexual risk behaviors in Korea, a larger sample size than expected is needed to assess the sensitivity of CIN2+ detection via self-samples.

A Versatile Nanowire Platform for Highly Efficient Isolation and Direct PCR-free Colorimetric Detection of Human Papillomavirus DNA from Unprocessed Urine.

Purpose: As human papillomavirus (HPV) is primarily responsible for the development of cervical cancer, significant efforts have been devoted to develop novel strategies for detecting and identifying HPV DNA in urine. The analysis of target DNA sequences in urine offers a potential alternative to conventional methods as a non-invasive clinical screening and diagnostic assessment tool for the detection of HPV. However, the lack of efficient approaches to isolate and directly detect HPV DNA in urine has restricted its potential clinical use. In this study, we demonstrated a novel approach of using polyethylenimine-conjugated magnetic polypyrrole nanowires (PEI-mPpy NWs) for the extraction, identification, and PCR-free colorimetric detection of high-risk strains of HPV DNA sequences, particularly HPV-16 and HPV-18, in urine specimens of cervical cancer patients. Materials and Methods: We fabricated and characterized polyethylenimine-conjugated magnetic nanowires (PEI/mPpy NWs). PEI/mPpy NWs-based HPV DNA isolation and detection strategy appears to be a cost-effective and practical technology with greater sensitivity and accuracy than other urine-based methods. Results: The analytical and clinical performance of PEI-mPpy NWs was evaluated and compared with those of cervical swabs, demonstrating a superior type-specific concordance rate of 100% between urine and cervical swabs, even when using a small volume of urine (300 µL). Conclusion: We envision that PEI-mPpy NWs provide substantive evidence for clinical diagnosis and management of HPV-associated disease with their excellent performance in the recovery and detection of HPV DNA from minimal amounts of urine samples.

Acceptability and feasibility of a community based participatory research project comparing cytology and urine HPV DNA testing for cervical cancer screening in Yap, Federated States of Micronesia.

Non-invasive, self-collected sampling methods for HPV DNA detection in women, which are reliable, efficient, and acceptable have the potential to address barriers to cervical cancer screening in underserved communities, including low-middle income countries (LMIC) such as the island nation of the Federated States of Micronesia (FSM). Urine-based HPV testing has not been rigorously evaluated in clinical trials. A pilot community-based participatory randomized control research project evaluated use of urine HPV testing as a more culturally- and human resource appropriate method of cervical cancer screening in Yap State, FSM. Women participated in a cervical screening intervention using pap vs. urine test (N=217). This manuscript described attitudes about screening feasibility and preferences. Stakeholders and women participants were interviewed (N=23), and a survey also evaluated women's screening preferences (N=217). Qualitative content thematic analysis with multiple coders identified themes from interviews on acceptability and feasibility of screening tests. Women research participants were comfortable with the urine test (95%), despite limitations in some to provide samples. While 82.0% indicated that they felt comfortable with Pap smear, they also preferred a clinician (42%) to do the Pap smear, explaining that they preferred having a trained worker instead of themselves to do tests. Women want to be screened but accessibility remains a challenge. Education and training of professionals and community members alike will improve clinical skills, research capacity, knowledge of screening tests and behaviors including prioritizing HPV screening and testing.

First-void urine: A potential biomarker source for triage of high-risk human papillomavirus infected women.

Great interest has been directed towards the use of first-void urine as a liquid biopsy for high-risk human papillomavirus DNA testing. Despite the high correlations established between urinary and cervical infections, human papillomavirus testing is unable to distinguish between productive and transforming high-risk infections that have the tendency to progress to cervical cancer. Thus far, investigations have been primarily confined to the identification of biomarkers for triage of high-risk human papillomavirus-positive women in cervicovaginal specimens and tissue biopsies. This paper reviews urinary biomarkers for cervical cancer and triage of high-risk human papillomavirus infections and elaborates on the opportunities and challenges that have emerged regarding the use of first-void urine as a liquid biopsy for the analysis of both morphological- (conventional cytology and novel immunohistochemical techniques) and molecular-based (HPV16/18 genotyping, host/viral gene methylation, RNA, and proteins) biomarkers. A literature search was performed in PubMed and Web of Science for studies investigating the use of urine as a biomarker source for cervical cancer screening. Five studies were identified reporting on biomarkers that are still in preclinical exploratory or clinical assay development phases and on assessments of non-invasive (urine) samples. Although large-scale validation studies are still needed, we conclude that methylation of both host and viral genes in urine has been proven feasible for use as a molecular cervical cancer triage and screening biomarker in phase two studies. This is especially promising and underscores our hypothesis that human papillomavirus DNA and candidate human and viral biomarkers are washed away with the initial, first-void urine, together with exfoliated cells, debris and impurities that line the urethra opening. Similar to the limitations of self-collected cervicovaginal samples, first-void urine will likely not fulfil the high-quality cellularity standards required for morphological biomarkers. Molecular biomarkers will likely overcome this issue to yield high-throughput, objective, and reproducible results. When using proper sampling, transport, storage, preanalytical biomarker concentration techniques, and clinically validated assays, first-void urine is expected to be a valuable source of molecular biomarkers for cervical cancer screening. Furthermore, as first-void urine can be easily and non-invasively collected, it is a highly preferred technique among women and offers the ability to test both primary high-risk human papillomavirus and biomarkers in the same sample. In addition, the use of first-void urine confers opportunities to reduce loss-to follow-up and non-adherence to screening subjects.

HPV testing in first-void urine provides sensitivity for CIN2+ detection comparable with a smear taken by a clinician or a brush-based self-sample: cross-sectional data from a triage population.

OBJECTIVE: To compare the sensitivity of high-risk human papillomavirus (hrHPV) and genotype detection in self-collected urine samples in the morning (U1), and later on (U2), brush-based self-samples (SS), and clinician-taken smears (CTS) for detecting cervical intraepithelial neoplasia grade 2+ (CIN2+) in a colposcopic referral population. DESIGN: Cross-sectional single-centre study. SETTING: A colposcopy clinic in Spain. POPULATION: A cohort of 113 women referred for colposcopy after an abnormal Pap smear. METHODS: Women undergoing colposcopy with biopsy for abnormal Pap smears were sent a device (Colli-Pee™, Novosanis, Wijnegem, Belgium) to collect U1 on the morning of colposcopy. U2, CTS, and SS (Evalyn brush™, Rovers Medical Devices B.V., Oss, the Netherlands) were also analysed. All samples were tested for HPV DNA using the analytically sensitive SPF10-DEIA-LiPA25 assay and the clinically validated GP5+/6+-EIA-LMNX. MAIN OUTCOME MEASURES: Histologically confirmed CIN2+ and hrHPV positivity for 14 high-risk HPV types. RESULTS: Samples from 91 patients were analysed. All CIN3 cases (n = 6) tested positive for hrHPV in CTS, SS, U1, and U2 with both HPV assays. Sensitivity for CIN2+ with the SPF10 system was 100, 100, 95, and 100%, respectively. With the GP5+/6+ assay, sensitivity was 95% in all sample types. The sensitivities and specificities for both tests on each of the sample types did not significantly differ. There was 10-14% discordance on hrHPV genotype. CONCLUSIONS: CIN2+ detection using HPV testing of U1 shows a sensitivity similar to that of CTS or brush-based SS, and is convenient. There was substantial to almost excellent agreement between all samples on genotype with both hrHPV assays. There was no advantage in testing U1 compared with U2 samples. TWEETABLE ABSTRACT: Similar CIN2+ sensitivity for HPV testing in first-void urine, physician-taken smear and brush-based self-sample.

Performance and Diagnostic Accuracy of a Urine-Based Human Papillomavirus Assay in a Referral Population.

Background: Human papillomavirus (HPV) testing from clinician-collected cervical and self-collected cervico-vaginal samples is more sensitive for detecting CIN2+/CIN3+ than cytology-based screening, stimulating interest in HPV testing from urine. The objective was to determine the performance of the Trovagene HPV test for the detection of CIN2+ from urine and PreservCyt cervical samples.Methods: Women referred for colposcopy at St Mary's Hospital (London, United Kingdom), following abnormal cytology, were recruited to this diagnostic accuracy study by convenience sampling (September 2011 to April 2013). A total of 501 paired urine and cervical samples were collected. Primary outcomes were sensitivity for CIN2+/CIN3+ and specificity for

Accuracy of urinary human papillomavirus testing for the presence of cervical human papillomaviruses and higher grades of cervical intraepithelial neoplasia.

BACKGROUND: Although urine-based testing for human papillomavirus (HPV) is being explored as a practical approach for cervical cancer screening, whether the results differ by age, race, or indicators of excess body weight or in populations exposed to HPV vaccines has not been documented by previous studies. The purpose of this study was to determine the accuracy of urinary HPV testing for the presence of cervical HPVs and high-grade cervical intraepithelial lesions (grade 2 and 3 cervical intraepithelial neoplasia [CIN]) by the aforementioned population characteristics. METHODS: The study population consisted of 502 women diagnosed with different grades of CIN. HPV testing was performed with paired urine and cervical cell DNA with the Roche Diagnostics Linear Array test. Agreement coefficient 1 and probabilities were calculated to determine the accuracy of urinary HPV testing for the presence of cervical HPVs and CIN lesions. RESULTS: Substantial to almost perfect agreement (0.66-0.83) was observed in the detection of any HPV genotype in urine specimens versus cervical specimens, regardless of the population characteristics. Although the positive predictive value for the detection of CIN lesions was relatively low, the negative predictive value for CIN-3 was high (≥90%) among women positive for any of the urinary or cervical high-risk human papillomavirus (HR-HPV) genotypes or HPV genotypes not included in currently available HPV vaccines. CONCLUSIONS: The results demonstrate that urinary HPV testing provides highly satisfactory results for excluding the possibility of any cervical HPV infections, including HPV types not included in vaccines and CIN lesions associated with any HR-HPV, regardless of a woman's age, race, or excess body weight. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2836-2844. © 2016 American Cancer Society.

Comparison of initial stream urine samples and cervical samples for detection of human papillomavirus.

BACKGROUND: Uterine cervical cancer is a treatable and preventable cancer. Medical efforts to reduce rates of cervical cancer focus on the promotion of human papillomavirus (HPV) vaccination and the promotion of routine cervical cancer screening done by cervical cytology and cervical HPV testing. Urine-based HPV testing would be simple and noninvasive approach to screen for cervical cancer. METHODS: Two biospecimens (clinician-taken sample from cervix and initial stream urine sample) were provided from a total of 240 healthy women attending for cancer screening provided for HPV testing. We have assessed the HPV detection rates among cervical samples and pellet fraction of urine samples using HPV test (Anyplex™ II HPV28 Detection kit, Seegene, Korea). RESULTS: Among 240 samples screened, HPV prevalence was 42.9% in pellet fractions of urine samples. The agreement between the two kinds of samples was 98.4%, k = 0.792. Discordant results were observed in 27 cases; 5 were positive only by urine samples and 22 were positive only by smear samples. Sensitivity and specificity for all HPV DNA in pellet fractions of urine using cervical samples as reference was 68.4% and 99.9%. CONCLUSIONS: Comparing methodologies of collection of samples for HPV detection, they showed the higher agreements for almost genotypes between cervical samples and pellet fractions of urine samples. These results suggest that urine could be a good noninvasive tool to monitor HPV infection in women. Additional research in a larger and general screening population would be needed.

Detection of Genital HPV Infection Using Urine Samples: a Population Based Study in India.

BACKGROUND: Cervical cancer is the second commonest cancer among Indian women and its association with human papilloma virus (HPV) is well established. This preventable cancer accounts for the maximum number of cancer related deaths among rural Indian women. Unlike in developed countries there are no organized cervical cancer screening programmes in India due to lack of resources and manpower. OBJECTIVE: To detect genital HPV infection using urine samples among asymptomatic rural women in the age group of 18-65 years. MATERIALS AND METHODS: The study area chosen was Perdoor village in Udupi Taluk, Karnataka State and all the women in the age group of 18-65 years formed the study cohort. A cross sectional study was conducted by house visits and 1,305 women were enrolled in the study. After taking written informed consent a data sheet was filled and early stream random urine samples were collected, transported to a laboratory at 4OC and aliquoted. Samples were tested using nested HPV PCR with PGMY09/11 and GP5+/6+ primers. Positive cases were genotyped by sequence analysis. RESULTS: Study participants included 1,134 sexually active and 171 unmarried women with a mean age at marriage of 22.1 (SD=3.9) years. Study area showed high female literacy rate of 86.6%. Five urine samples tested positive for HPV DNA (0.4%). CONCLUSIONS: We found very low genital HPV infection rate among women from monogamous community. This is the first major population based study carried out among asymptomatic rural women to detect genital HPV infectio from Karnataka using urine samples.

Application of SELDI-TOF in N-glycopeptides profiling of the urine from patients with endometrial, ovarian and cervical cancer.

PURPOSE: Endometrial (ECa), ovarian (OCa) and cervical (CCa) cancers are among 10 of the most common cancers affecting women worldwide. Cancers are known to cause some proteins to be differentially glycosylated or aberrantly excreted in the urine, which can be used as biomarkers. Since ECa, OCa and CCa are difficult to diagnose at the early stage, the aim of the present study was to identify a panel of new biomarkers for early detection of the cancers using surface-enhanced laser desorption/ionization-time-of-flight (SELDI-TOF) technology. Identification of early biomarkers that are specific and efficient can increase the survival rate of the patients. EXPERIMENTAL DESIGN: Digested urinary proteins from patients with ECa, OCa and CCa were incubated on the champedak mannose-binding (CMB) lectin-immobilized PS10 chip. The lectin-captured glycopeptides were detected with SELDI-TOF mass spectrometry and followed by biomarker wizard analysis. RESULTS: Peaks m/z 1201 and 1449 were detected as potential group discriminators. The peak m/z 1201 could distinguish OCa from CCa and ECa and its sensitivity and specificity were 100%. For m/z 1449, it was able to differentiate ECa from the other two types of cancer. CONCLUSIONS: The findings of this study suggest urinary glycopeptides m/z 1201 and 1449 may serve as potential biomarkers for the early detection of ECa, OCa and CCa, although this requires further extensive validation on clinically representative populations.

[Value of urine sediment analyzer in the screening of urinary tract infection in cancer patients].

OBJECTIVE: To evaluate the value of urine sediment analyzer in the screening of clinically suspected urinary tract infection (UTI) in cancer patients. METHODS: The results of bacterial count of 1 053 midstream urine samples by UF-1000i urine sediment analyzer (UF-1000i urine sediment analyzer, UF-1000i) were compared with the results of bacterial culture. Moreover, the results of distinguishing bacterial species by the bacterial scattergram were compared with the results of bacteria culture. At the same time, the sensitivity, specificity, positive predictive value and negative predictive value of UF-1000i analyzer for UTI screening were evaluated. RESULTS: Of all the 1 053 samples, the top three bacteria were E. coli, Enterococci and P. aeruginosa. The top three malignant tumors of UTI were bladder, lung cancer and cervical cancers. The positive rate of UF-1000i analyzer was 20% (211/1 053), and that of bacteria culture was 17.9% (188/1 053). There was statistically no significant difference in the positive rates between the two methods (χ(2)=1.636, P>0.05), and the two methods had a considerable consistency (Kappa=0.756). Compared with the clinical diagnosis, UTI screening by UF-1000i analyzer showed a sensitivity of 79.6% (160/201), specificity of 95.5% (814/852), positive predictive value of 80.8% (160/198) and negative predictive value of 95.2%(814/855). The distribution of cocci and bacilli acquired by the bacterial scattergram was basically in accordance with the results of bacterial culture. CONCLUSIONS: Bacterial count by UF-1000i analyzer plays an important role in early screening of UTI, and the bacterial scattergram may help to distinguish bacterial species, providing reference for the use of antibiotics in early medication.