Clinical significance of HPV-HC2 in diagnosis and prognosis of cervical lesions: a retrospective study

Background: To evaluate the human papillomavirus HC2 different range detection values and their clinical significance in prediction of CIN lesions grades as well as their role in the follow-up outcome after treatment.Methods: Using the hybrid capture 2 to detect and measure the HPV and the viral load quantity, we enrolled a total of 527 HPV positive women. All patients underwent thin prep liquid-based cytology test (TCT) and only 325 underwent colposcopy guided biopsy due to abnormal cytology results. All cytology and biopsy results were collected and analyzed according to the HPV viral load. Among these patients 108 patients were followed during 2years post-operatives and their prognosis results were collected and analyzed.Results: The proportion and severity of cytological abnormalities was positively correlated with the HPV-HC2 viral load (P<0.05). There was a positive correlation between cervical biopsy results and the HPV viral load P <0.05). The more the HPV-HC2 viral load was, the higher CIN2-3 grade percentage was getting. However no statically significant correlation was found between the HPV-HC2 viral load and the follow up outcomes after treatment (P>0.05).Conclusions: High HPV-HC2 viral load is significantly associated with the severity of cervical lesions (CIN), however it does not predict any further prognosis on follow-up after treatment.

Clinical Significance of an HPV DNA Chip Test with Emphasis on HPV-16 and/or HPV-18 Detection in Korean Gynecological Patients

BACKGROUND: Human papillomavirus (HPV) is a major risk factor for cervical cancer. METHODS: We evaluated the clinical significance of the HPV DNA chip genotyping assay (MyHPV chip, Mygene Co.) compared with the Hybrid Capture 2 (HC2) chemiluminescent nucleic acid hybridization kit (Digene Corp.) in 867 patients. RESULTS: The concordance rate between the MyHPV chip and HC2 was 79.4% (kappa coefficient, κ = 0.55). The sensitivity and specificity of both HPV tests were very similar (approximately 85% and 50%, respectively). The addition of HPV result (either MyHPV chip or HC2) to cytology improved the sensitivity (95%, each) but reduced the specificity (approximately 30%, each) compared with the HPV test or cytology alone. Based on the MyHPV chip results, the odds ratio (OR) for ≥ high-grade squamous intraepithelial lesions (HSILs) was 9.9 in the HPV-16/18 (+) group and 3.7 in the non-16/18 high-risk (HR)-HPV (+) group. Based on the HC2 results, the OR for ≥ HSILs was 5.9 in the HR-HPV (+) group. When considering only patients with cytological diagnoses of “negative for intraepithelial lesion or malignancy” and “atypical squamous cell or atypical glandular cell,” based on the MyHPV chip results, the ORs for ≥ HSILs were 6.8 and 11.7, respectively, in the HPV-16/18 (+) group. CONCLUSIONS: The sensitivity and specificity of the MyHPV chip test are similar to the HC2. Detecting HPV-16/18 with an HPV DNA chip test, which is commonly used in many Asian countries, is useful in assessing the risk of high-grade cervical lesions.

Prevalence of HR-HPV and risk factors associated with the development of lesion cervical precousor of cervical cancer, a sample of the Curitiba metropolitan region, case-control study / Prevalência do HPV-AR e fatores de risco associados ao desenvolvimento de lesões cervicais precursoras do câncer cervical, numa amostra da região metropolitana de Curitiba, estudo caso-controle

Objective: Characterize the risk factors associated with the development of cervical intraepithelial neoplasia (CIN) and determine the prevalence of Highrisk Human Papillomavirus (HR-HPV) infection in women without cytological abnormalities and women diagnose with CIN 2 and 3, living in metropolitan region Curitiba, Parana state, Brazil. Material and Methods: Case-control study consisting of 382 women without cytological abnormalities, 233 women with high-grade intraepithelial lesions, which were subdivided in 131 women with CIN 2 and 102 women with CIN 3 diagnose by histological analysis of the cervical segment conical excision material. The age range of the women in the study was 15-45 years old, collected in the period of 2009 to 2012. The detection of HR-HPV DNA was performed by Hybrid Capture 2 test (CH2)...

Objetivo: Caracterizar os fatores de risco associados ao desenvolvimento de neoplasias intraepiteliais cervicais (NIC) e verificar a prevalência da infecçãopelo HPV de alto risco (HPV-AR) em mulheres sem anormalidade citológicas e com NIC 2 e 3, residentes na Região Metropolitana de Curitiba, Paraná,Brasil. Materiais e Métodos: Estudo caso-controle, composto por 382 mulheres sem anormalidades citológicas, 233 mulheres com lesão intraepitelial de alto grau, sendo estas subdivididas em 131 mulheres com NIC 2 e 102 com NIC 3 após a análise histológica do material da excisão cônica do segmento do colo do útero. A faixa etária das mulheres do estudo foi de 15 a 45 anos, coletadas no período de 2009 a 2012. A detecção do DNA do HPV-AR foi realizada pelo teste Captura Híbrida (CH2)...

Human papillomavirus false positive cytological diagnosis in low grade squamous intraepithelial lesion

The purpose of this study was to investigate the number of Human Papillomavirus false positive cytological diagnosis in low grade squamous intraepithelial lesions (LSIL). Three hundred and two women who assisted to an Out-Patient Gynecologic Clinic in Maracaibo, Venezuela, were recruited for this study. Each patient had the Pap smear and a cervical swab for Hybrid Capture 2 (HC2). Three cytotechnologists reviewed the Pap smears and two pathologists rescreened all of them. The cytotechnologists reported 161 (53.3 percent) Pap smears negatives for intraepithelial lesion (IL) or malignancy, and 141 cases (46.7 percent) with epithelial abnormalities. They reported 46 percent of 302 patients with HPV infection in Pap smear slides. The pathologists found that 241 (79.8 percent) Pap smears were negatives for IL or malignancy and 61 (20.2 percent), with abnormal Pap smears. They found 14.6 percent HPV infection in all Pap smears (p<0.0001; 46 percent vs 14.6 percent). The HC2 study showed that 47 samples (15.6 percent) were positive for HPV. The study found that 114 Pap smears (False Positive: 85 percent) of 134 reported by the cytotechnologists and 24 (False Positive: 43 percent) of 56 cytologies reported by the pathologists as LSIL, were negative for HPV infection determined by HC2 (p<0.00003). The present study suggests that the cytotechnologists overdiagnosed cellular changes associated with HPV infection in the Pap smear, increasing the FP cytological diagnosis of LSIL.

El presente trabajo tuvo por objeto el investigar el número de falsos positivos reportados en la citología cervicovaginal (CCV) de la presencia del Virus del Papiloma Humano (VPH) con diagnóstico de Lesión Intraepitelial Escamosa de bajo grado (LIE-BG). Se estudiaron 302 mujeres que asistieron a la Consulta de Patología de Cuello Uterino del Hospital Manuel Noriega Trigo, en Maracaibo, Venezuela. A cada paciente se le practicaron una CCV y muestra para la captura de híbridos 2 (CH2). Tres citotecnólogos y 2 patólogos estudiaron las CCV. Los citotecnólogos reportaron 161(53,3 por ciento) de CCV negativas para lesión intraepitelial o malignidad y 141 casos (46,7 por ciento) con anomalías epiteliales. Éstos encontraron 46 por ciento de presencia de VPH en las 302 CCV. Los patólogos reportaron 241 CCV (79,8 por ciento) negativas y 61 CCV (20,2 por ciento) anormales. Estos encontraron en 14,6 por ciento de las CCV, la presencia de VPH (p < 0, 0001; 46 por ciento vs 14,6 por ciento). La CH2 mostró que 47 muestras (15, 6 por ciento) fueron positivas a VPH. Esta investigación mostró que 112 CCV de 134 (Falso Positivo: 85 por ciento) reportados por los citotecnólogos y 24 de 56 CCV (Falso Positivo: 43 por ciento) reportados por los patólogos como LIE-BG, fueron negativos a la infección del VPH determinados por la CH2 (p < 0,00003). La investigación sugiere un sobrediagnóstico de la presencia de cambios celulares debidos al VPH en la CCV, por parte de los citotecnólogos, incrementando los falsos positivos de la presencia del VPH en CCV con diagnóstico de LIE-BG.

Prevalence and risk factors of human papillomavirus infection in asymptomatic women in a Venezuelan urban area

The purpose of this study was to investigate the prevalence and risk factors of genital human papillomavirus (HPV) infection in asymptomatic women, using the HPV DNA Hybrid Capture 2 (HC2) test. Three hundred and two women who attended the Out-Patient Gynecological Clinic of a tertiary level hospital, in a Venezuelan urban area, were selected for the study. A pap smear, a cervical swab for HC2 and gynecological exam were performed to each patient. The HC2 testing showed that 47 samples (15.6%) were positive to HPV. Forty patients (13.2%) were positive to high risk-HPV (HR-HPV) and 11 (3.6%) were positive to low-risk-HPV (LR-HPV). The prevalence of HPV infections was higher for women under 35 years (51.1%; p < 0.02), and decreased to 6.4% for women 65 years old. Women who had not finished high school had a higher prevalence of HPV infection (p < 0.035). Twenty six (42.6%) of 61 pathological Pap smears were positives to HPV infection. A statistically significant difference was found when HPV infection was compared in normal and abnormal Pap smear (HSIL+LSIL; p<0.0001). Twenty four of 56 (43%) women with diagnosis of LSIL, and 2(40%) of 5 with diagnosis of HSIL were positive for HPV infection. A statistically significant difference was found when we compared HPV infection in negative Pap smears and those with LSIL (p<0.001). The present study found that the prevalence of HPV infection in asymptomatic Venezuelan women who attended a tertiary level hospital was 15.6%. HPV infection was more frequent in young adult, and in women with low educational level.

El propósito de este estudio fue investigar la prevalencia y factores de riesgo que influencia la presencia de la infección por el virus del papiloma humano (VPH) en pacientes asintomáticas que asistieron a un hospital nivel 3 en un área urbana venezolana. Se estudiaron las pacientes que acudieron a la Consulta de Patología del Cuello Uterino del Hospital Manuel Noriega Trigo. A cada paciente se le realizó una historia clínica, toma de citología cervico-vaginal y una muestra del cérvix para captura de híbridos 2(CH2). Se incluyeron 302 pacientes. La CH2 mostró 47 muestras (15,6%) positivas al VPH. Cuarenta mujeres (13,2%) fueron positivas a VPH de alto riesgo (VPH-AR) y 11 (3,6%) a VPH de bajo riesgo (VPH-BR). La prevalencia de la infección por VPH fue más alta en mujeres 35 años (51,1%; p < 0,02) y disminuyó a un 6,4% en mujeres 65 años. Las pacientes que no habían terminado los estudios de bachillerato presentaron un prevalencia más elevada del VPH (p < 0,035). Veinte y seis (42,6%) de 61 CCV patológicas fueron positivas a la infección del VPH. Una diferencia estadísticamente significativa fue encontrada cuando se comparó la presencia del VPH en las CCV normales con las CCV anormales (Lesión Intraepitelial Escamosa de Alto y Bajo Grado-LIE-AG y LIE-BG; p < 0,0001). Veinte y cuatro de 56 (43%) mujeres con diagnostico de LIE-BG, y 2(40%) de 5 con diagnóstico de LIE-AG fueron positivos a la presencia del VPH. Se encontró una diferencia estadísticamente significativa cuando se comparó la presencia de infección por el VPH en CCV normales y CCV con LIE-BG (p < 0,001). El presente estudio encontró una prevalencia de la infección por el VPH en mujeres asintomáticas que asisten a un hospital nivel 3 de 15,6% en área urbana venezolana. Fue más frecuente en mujeres jóvenes y de bajo nivel educacional.

Predictive Value of Detection of hTERC Gene Copy Number in Cervical Epithelial Cells by means of Fluorescence in situ Hybridization and Human Papilloma Virus Testing for Cervical Intraepithelial Neoplasia / 中华医院感染学杂志

OBJECTIVE To explore the predictive value of human telomerase RNA gene component(hTERC) gene amplification and high-risk human papilomavirus(HR-HPV) testing in cervical intraepithelial neoplasia(CIN) as a marker for early diagnosis of cervix carcinoma.METHODS Fluorescence in situ hybridization(FISH) was used to detect the amplification of hTERC of cervical epithelial cells in 72 cases.By using hybrid capture 2(HC-2),two types of the HR-HPV DNA(HPV16/18) of each case were detected.Then,the results were compared with the pathologic diagnosis.The dual-color probe we used was GLP TERC/CSP 3.HeLa cells and lymphocytes from normal marrow were the positive control,while the cervical specimens from healthy outpatients were the negative control.RESULTS hTERC Gene amplification of specimens was tested in 72 cases,the positive amplification rate of hTERC gene in the cervicitis/CINⅠgroup and normal,compared to the cervical carcinomas(100%) and CIN Ⅱ/Ⅲ(68.75%),which showed a significant difference.The rates in CINⅡ and CINⅢ were 60.00% and 83.33%,respectively,which showed a significant difference compared with normal and CINⅠ/inflammation groups.hTERC gene amplification was positive in both HeLa cells and lymphocytes from normal marrow and HC-2 testing was positive in 32 cases of patients containing 11 cases of CINⅡ/Ⅲ,3 cases of cervical cancer,18 cases of cervicitis/CIN1 diagnosed.The positive predictive value(PPV) and specificity(Sp) of hTERC for the high-grade CIN was significantly higher than the PPV and Sp of HC-2 HR-HPV testing.CONCLUSIONS hTERC Gene involves in the progression and occurrence of cervical intraepithelial neoplasia and cervical squamous carcinoma.As a marker for early diagnosis of cervical intraepithelial neoplasia and cervical squamous carcinoma,the FISH method for hTERC gene is more reliable to differentiate the malignant diseases from the benign ones in cervixes than HC-2 HR-HPV DNA testing.The combined detection of HR-HPV and hTERC gene will provide more effective and suitable management to enhance the early diagnosis rate of cervical intraepithelial neoplasia and cervical squamous carcinoma.

Low prevalence of high risk human papillomavirus in normal oral mucosa by hybrid capture 2

High risk human papillomavirus (HR-HPV) are recognized as a necessary factor to development cervical cancer. During the last decade many studies have found HR-HPV in oral squamous cell carcinoma (OSCC) and normal oral mucosa, however the association between HR-HPV and OSCC is still uncertain. The aim of the study was to determine DNA HR-HPV in normal oral cavity of healthy adults. A cross-sectional study was performed; samples from 77 patients with normal oral cavity were collected at the Dentistry school, Autonomous University of Yucatan, Merida, Yucatan, México. HR-HPV was detected by hybrid capture 2. One sample out of 77(1.2 percent) was positive for HR-PVH. It was from a man of 50 years old. HR-HPV is present in low rate among healthy oral mucosa. Hybrid capture 2 could be a good methodology for large epidemiology studies.

Papilomavírus humano de alto risco (HR-HPV) é um fator reconhecido como necessário para o desenvolvimento de câncer cervical. Na última década vários estudos encontraram HR-HPV em OSCC (oral squamous cell carcinoma) e em mucosa oral normal, mas a associação entre HR-HPV e OSCC não é bem conhecida. O objetivo desse estudo foi determinar DNA de HR-HPV na cavidade oral normal de adultos saudáveis. Realizou-se um estudo cross-sectional com amostras da cavidade oral normal de 77 pacientes da Escola de Odontologia da Autonomous University of Yucatan, Merida, Yucatan, México. HR-HPV foi detectado através de Captura Híbrida 2. Uma amostra em 77 (1,2 por cento) foi positiva para HR-PVH e era proveniente de um homem de 50 anos de idade. Concluiu-se que HR-HPV tem baixa prevalência na mucosa oral normal e a Captura Híbrida 2 pode ser um método adequado para estudos epidemiológicos.

The clinical value of using xMAP technology for detection of high-risk human papillomavirus / 肿瘤

Objective: To explore the clinical values of using flexible multi-analyte profiling (xMAP) technology for detection of high-risk human papillomavirus (HR-HPV). Methods: Six hundred and thirty eight cervical exfoliated cell samples were collected from women who lived in the region with high-incidence of cervical cancer in Shanxi province. The samples were tested with xMAP technology and Hybrid Capture 2 ® Assay (hc2). Pathological diagnosis was used as a hallmark to evaluate the detection results. HR-HPV infection rate and its genotyping distribution were analyzed and the coincidence of two methods above was assessed. Results: The sensitivity, specificity and accuracy of xMAP technology were 77.78%, 93.59% and 92.42%, respectively. The negative and positive predictive values were 98.13% and 49.30%, respectively. The prevalence rate of HR-HPV was 11.7%. HPV16 and 52 were the dominant types in non-neoplastic disease and cervical intraepithelial neoplasia (CIN) grade 1; HPV16 and 58 were the most common types in CIN2 samples; HPV16 was the most frequent type in CIN3 and cervical cancer. The lesion progress was positively related to the infection rate of HPV16, 52 or 58 (P<0.01). The Kappa value for agreement between xMAP technology and hc2 was 0.60. Conclusions: Compared with the hc2 test, the xMAP technology was highly specific, and the sensitivity is 77.78%. The agreement of these two methods is satisfactory. More improvements should be made to elevate the sensitivity of xMAP method and to increase the numbers of genotypes that can be detected.

Comparison of the AMPLICOR human papillomavirus (HPV) Test and the Hybrid Capture 2 Assay for detection of high-risk HPV / 대한산부인과학회지

OBJECTIVE: The purpose of this study was to determine the efficacy of the AMPLICOR HPV test in comparison with the Hybrid Capture 2 (HC2) test in detecting HR HPV. METHODS: One hundred and fifty-three consecutive women attending the Colposcopy Clinic were included and cervical scrape specimens were tested for the presence of 13 HR HPV genotypes by both AMPLICOR HPV test and HC2 assay. RESULTS: The prevalence of HR HPV was 53/153 (34.6%) and 52/153 (34.0%) by AMPLICOR HPV test and HC2 assay, respectively. When discordant results were observed between AMPLICOR HPV test and HC2 assay, we used the HPV genotyping DNA chip and DNA sequence analysis, as reference standards. Concordant results were obtained for 128 (83.7%) of the 153 samples (Cohen's kappa=0.63, p<0.001). The genotyping showed that no HR HPV was detected in the 10 AMPLICOR negative HC2 positive samples, while HR HPV genotype was found in 3/13 (23.1%) AMPLICOR positive HC2 negative samples. The detection rates of HR HPV with AMPLICOR HPV test and HC2 assay were 38.7% and 48.4%, respectively, in CIN1; 95.0% and 100%, respectively, in CIN3/cancer. HPV positivity of AMPLICOR HPV test and HC2 assay increased linearly with the increasing grade of cytology or histology (p<0.001). In detecting high grade (CIN2+) lesions, sensitivities were 90.9% (CI, 75.9~97.0%), 95.5% (CI, 81.9~99.0%), respectively, for AMPLICOR HPV test and HC2 assay (p=1.00). The specificities of AMPLICOR HPV test and HC2 assay were 72.7% (CI, 64.3~79.8%) and 69.3% (CI, 60.7~76.7%), respectively (p=0.75). CONCLUSIONS: AMPLICOR HPV test is comparable to HC2 assay for detection of HR HPV, with similar sensitivity and specificity in detecting CIN2+ lesions. AMPLICOR HPV test can be considered clinically useful for detection of HR HPV. However, more data are clearly needed on the performance of AMPLICOR HPV test as a screening tool.