Human Papillomavirus DNA Chip Test Research Articles

Comparison of the performance of the PANArray™ HPV test and DNA chip test for genotyping of human papillomavirus in cervical swabs

The aim of this study was to evaluate the recently developed PANArray™ Human papilloma virus (HPV) kit for detection and genotyping of 19 high-risk and 13 low-risk HPV types, and compare it with the commercially available DNA chip kit genotyping of 24 HPVs. We collected cervical swabs from 741 patients with various stages of invasive cervical carcinoma being treated at the Samsung Medical Center. The overall HPV positivity rate was 73% using PANArrayTM HPV and 72.1% with the DNA chip, and no statistically significant differences were found with respect to the cytology grade. Comparing the results of the two chips, concordant results were found in 637/741 samples (85.9%), compatible in 69/741 (9.3%) and discordant in 35/741 (4.7%). Type-specific sequencing analysis of all samples revealed a 99.7% confirmation of PANArrayTM HPV genotyping results, compared to 91.0% of DNA chip. The PANArrayTM HPV test thus proved to be highly sensitive and accurate even when multiple HPV infections were present.

Significance of human papillomavirus genotyping with high-grade cervical intraepithelial neoplasia treated by a loop electrosurgical excision procedure

This study was conducted to determine whether the human papillomavirus (HPV) genotype by the HPV DNA chip test (HDC) is predictive of residual or recurrent high-grade cervical intraepithelial neoplasia (CIN) 2-3 following a loop electrosurgical excision procedure (LEEP). Between January 2001-February 2007, 672 patients with CIN2-3 were treated by a LEEP and followed up with cytology, the hybrid capture II assay, and the HDC. A total of 37 (5.5%) patients developed a recurrence, and those who developed a recurrence tested positive for the same high-risk (HR) HPV genotype before and after the LEEP. The same HR-HPV genotype by the HDC during the follow-up had a sensitivity and negative predictive value of 100% for detecting residual/recurrent disease. Persistent HPV-16 and HPV-18 were significantly associated with recurrent CIN2-3 (P < .05). Persistent infection with the same HR-HPV genotype, especially HPV-16 and HPV-18, should be considered a risk factor for developing residual/recurrent CIN2-3.

The Analysis and Clinical Usefulness of HPV DNA Chip Test in the Uterine Cervix

The Analysis and Clinical Usefulness of HPV DNA Chip Test in the Uterine Cervix

Comparison of the Hybrid Capture II Assay With the Human Papillomavirus DNA Chip Test for the Detection of High-Grade Cervical Lesions

Cervical intraepithelial neoplasia (CIN) 2 is used as the threshold for treatment decisions. This study was conducted to evaluate the clinical efficacy of the Hybrid Capture II assay (HC2) and the human papillomavirus (HPV) DNA chip test (HDC) for detecting HPV in high-grade cervical lesions CIN2 or greater, including adenocarcinoma (CIN2+). Seven hundred forty-one women with abnormal cervical cytology were evaluated with the HC2, the HDC, and histological assessment of the cervix. The overall agreement of the 2 HPV tests was 88.8% (kappa value, 0.61). Of 615 high-risk HPV-positive specimens by the HC2, 571 (92.8%) were HDC-positive. Both tests were performed similarly on CIN2+ samples; the sensitivities of the HC2 and HDC as predictors of CIN2+ were 93.4 and 92.6%, respectively. In 83 cases of discrepancies between the HC2 and HDC, genotyping of 39 HC2-negative/HDC-positive cases revealed 13 HPV-53, 8 HPV-58, 7 HPV-16, 6 HPV-18, 2 HPV-68, 1 HPV-31, 1 HPV-45, and 1 HPV-66. In 515 patients with CIN2+, HPV-16 (45.0%) was the most common type; the next most common types were HPV-58 (20.8%), HPV-18 (16.1%), HPV-31 (6.6%), and HPV-33 (6.6%). Human papillomavirus types 16, 58, and 18 were more likely associated with CIN2+ (P < 0.05). In conclusion, the HDC is a reliable diagnostic tool for the detection of CIN2+. In addition, the HDC provides useful information regarding viral genotypes.

Analysis of HPV-other Samples by Performing HPV DNA Sequencing

Background : HPV-other samples are designated as being positive on HPV-PCR, but negative when using specific HPV hybridization probes. We wanted to determine the types on the HPV-other samples by performing sequencing, and to know the pathologic status of the uterine cervix according to the HPV type detected on sequencing. Methods : For HPV genotying, we used the commercially available HPV DNA Chip test, which contains 15 types of highrisk HPV and 9 types of low-risk HPV. The HPV DNA sequencing was performed for the HPVother samples of 209 patients who subsequently underwent cervical biopsy. Results : For 204 of the 209 samples, the HPV types detected by sequencing were absent types at used HPV DNA chip. For the remaining 5 samples, sequencing was impossible due to mixed peaks. HPV-81 (19.6%), HPV-61 (18.6%), HPV-62 (16.7%) and HPV-84 (13.9%) were frequently detected. For the HPV-81, -62, -71, and -72 samples, most of the samples displayed normal or LSIL. However, HPV-84 and -61 were more associated with HSIL or worse, as compared to the other types. Conclusion : HPV-81, -61, -62 and -84 were frequently found on sequencing analysis of the HPV-other samples. The pathologic status was diverse, according to the HPV type detected on sequencing.

Clinical Efficacy of HPV DNA Chip Test in the Era of HPV Vaccination - 1,211 Cases, A Single Institution Study -

Human papillomavirus (HPV) prophylactic vaccines, bivalent types for HPV-16/18 with 70% prophylactic expectation, have been developed based on the genotypes found prevalent in the western countries, but little is known for those in Korea. Using a DNA chip test, we evaluated the clinical efficacy of HPV genotype based on cervical abnormalities. As the initial diagnostic tests, HPV DNA chip tests and Papanicolaou smear (PAP) were used for 1,211 subjects. Cervical colposcopy directed biopsies were performed for 626 among the 1,211 subjects within one month. The most frequently found genotypes in all HPV-positive specimens (n=445) were HPV-16 (22.0%), 58 (13.9%), 52 (11.0%), 51 (9.0%), 56 (8.5%), and 18 (7.2%). HPV prevalence was significantly higher in specimens where PAP and biopsy results were closer to malignancy. The HPV genotype distribution of the histologically confirmed cervical high-grade squamous intraepithelial lesions (HSIL) or carcinoma cases showed HPV-16, 58, 52, 18, and 33, in descending order. The HPV DNA chip sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the detection of cervical HSIL or carcinoma were 76.9%, 70.1%, 72.1%, and 75.8%, respectively, Of these, the sensitivity and NPV were higher than those of PAP. PPV and NPV of HPV-16 were 90.5% and 60.7%, respectively, being the highest among the genotypes. We confirmed that HPV-16 genotype was also very important for the diagnosis of HSIL and cervical carcinoma in Korea. However, contrary to the findings in the western countries, the prevalence of HPV-58 was higher than that of HPV-18. Moreover, as the other HPV genotype reports were rare in Korea, further studies are required with the HPV DNA chip test before the nationwide adoption of the vaccines.

Comparison of Clinical Efficacy between an HPV DNA Chip and a Hybrid-Capture II Assay in a Patient with Abnormal Colposcopic Findings

This study was performed to compare the efficacy between a DNA chip method and a Hybrid-Capture II assay (HC-II) for detecting human papillomavirus in patients with intraepithelial lesions of the uterine cervix. From May, 2005, to June, 2006, 192 patients with abnormal colposcopic findings received cervical cytology, HC-II and HPV DNA chip tests, and colposcopic biopsy or conization. We compared the results of HC-II and HPV DNA chip in conjunction with liquid based cervical cytology (LBCC) and confirmed the results of biopsy or conization. The sensitivity of the HPV DNA chip test was higher than HC-II or LBCC. The HPV DNA chip in conjunction with LBCC showed higher sensitivity than any single method and higher sensitivity than HC-II with LBCC. We confirmed that the HPV DNA chip test was more sensitive for detecting HPV in cervical lesions than HC-II, and that it would provide more useful clinical information about HPV type and its multiple infections.

The Prevalence of Human Papilloma virus Infection in Sinonasal Inverted Papilloma Specimens Classified by Histological Grade

Histological analysis suggests that inverted papilloma (IP) tumorigenesis may occur through a stepwise series of discrete events. The association between human papilloma virus (HPV) and IP has been described at varying incidences. The purpose of this study was to evaluate the prevalence of the HPV subtypes in a large series of IP specimens classified by histological grade. Fifty-seven paraffin-embedded specimens of Korean population were available for study. Each specimen was graded according to a four-stage histological grading system (stages I and II, benign IP; stage III, dysplastic IP; stage IV, carcinoma arising from IP). A representative section of IP specimen was isolated through laser capture microdissection (7.5- to 10-mum laser spot size). Subsequently, DNA extraction and HPV genotyping with the HPV DNA chip test (Biomed Lab Co., Seoul, Korea) was performed. The HPV DNA chip contained 22 type-specific probes that consisted of 15 high-risk subtypes and 7 low-risk subtypes. Histological grading was as follows: 5, grade I; 23, grade II; 22, grade III; and 7, grade IV. Seven of 57 specimens (12.3%) showed HPV DNA. All of the HPV(+) cases showed HPV DNA in early grade (grades I and II) IP lesions. No higher grade (grades III and IV) IP tumors showed HPV DNA. Among the seven HPV(+) cases, five were high-risk subtypes and two were unspecified subtypes. HPV infection, mainly high-risk subtypes, occurs in benign IP as an early event during the multistep tumorigenesis of IP. Cumulative other genetic insults may be required to progress from benign IP (grades I and II) to dysplastic IP (grade III) and carcinoma arising from IP (grade IV).

Persistence of human papillomavirus as a predictor for treatment failure after loop electrosurgical excision procedure

We aimed to investigate whether postconization human papillomavirus (HPV) DNA testing can predict treatment failure and improve the accuracy of conventional follow-up in women with high-grade cervical intraepithelial neoplasia (CIN). Between March 2001 and October 2005, 120 patients with confirmed CIN 2 or 3 were treated with loop electrosurgical excision procedure (LEEP) and were enrolled. Six patients were lost to the follow-up. Postconization follow-up was performed at every 3-6 months during the first year and then annually. Specimens were tested for the presence of HPV, using the Hybrid Capture 2 (Digene Co, Gaithersburg, MD) and HPV DNA chip (Mygene Co, Seoul, Korea) test. Persistent HPV infection was defined as persistently (two times or more) positive HPV tests with the same HPV subtype(s) at initial diagnosis. Twenty-two (19.3%) patients showed treatment failure after conization. The only significant risk factor for redevelopment of CIN after conization was persistence of the same HPV subtype (P < 0.0001). And women with recurrent or residual CIN had higher HPV load during the 6-month follow-up postconization. In conclusion, the persistence of the same HPV subtype after LEEP conization was an important predictor of treatment failure. The follow-up protocol after conization of CIN should include both cervical cytology and HPV test, and HPV DNA chip test is needed to detect a persistent HPV infection.

The relationship between cytokines and HPV-16, HPV-16 E6, E7, and high-risk HPV viral load in the uterine cervix

To investigate intralesional cytokine levels in precancerous lesions of the uterine cervix and their relationship with human papillomavirus (HPV) type 16, HPV type 16 E6/E7, and high-risk HPV viral load. We performed a prospective study of 67 patients between May 2005 and December 2005. Hybrid Capture II testing was used to identify patients as high-risk HPV DNA-positive or -negative. HPV DNA Chip test was performed for HPV genotyping in all cases found to be HPV DNA-positive. Real-time PCR was used to quantify HPV-16 E6, E7, interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) transcripts. Among high-risk HPV-infected women, intralesional TNF-alpha, IL-6, IL-10, and IFN-gamma levels had no significant differences according to histologic grade. In multivariate logistic regression analysis, TNF-alpha, IL-6, IL-10, and IFN-gamma were not associated with HPV-16. Increased IFN-gamma was significantly associated with HPV-16 E6- and E7-positive (OR 28.197, 95% CI: 2.658-299.110; OR 19.617, 95% CI: 2.135-180.253, respectively), whereas TNF-alpha, IL-6, and IL-10 were not associated with HPV-16 E6 and E7. In multiple regression analysis, elevated IFN-gamma was significantly associated with increased HPV viral load (P=0.039), whereas TNF-alpha, IL-6, and IL-10 were not significantly associated with HPV viral load. Among HPV-infected women, IFN-gamma is significantly associated with HPV-16 E6, E7, and high-risk HPV viral load in the uterine cervix. Thus, increased intralesional IFN-gamma may be considered to be a prognostic marker for oncogenic potential of high-risk HPV.

Detection of HPV genotypes in cervical lesions by the HPV DNA Chip and sequencing

Objective. A newly introduced HPV detection technique in cervical lesion, the HPV DNA Chip test, contains 24 HPV probes and has the advantage of being able to detect 24 HPV types at once. We performed HPV DNA sequencing and compared the results with that of the HPV DNA Chip for evaluation of the accuracy of the DNA Chip test. Methods. The HPV DNA sequencing was performed in samples of 282 patients, where specific HPV type had been shown in HPV DNA Chip test. The sixteen cases where multiple HPV types had been found in HPV DNA Chip test were included in 282 cases. The sequencing was also performed in HPV-other type samples of 95 patients, where positive in HPV-PCR, but specific HPV type had not been found. Results. In 257 cases (91.1%) of 282 cases, the HPV types of the HPV DNA sequencing test were in agreement with types of the HPV DNA Chip. In 16 cases (5.7%), the sequencing types were different from the types of HPV DNA Chip. But, in 9 of 16 cases, types in HPV DNA sequencing were absent types in HPV DNA Chip test. The interpretation of HPV DNA sequencing was impossible in nine cases (3.2%). The HPV DNA sequencing test of 95 cases of HPV-other type showed that the sequencing types from 94 cases (98.9%) were absent types in HPV DNA Chip test. In sequencing test of HPV-other type, HPV-81 (20.0%), HPV-62 (14.7%), HPV-84 (13.7%), and HPV-61 (13.7%) were frequently detected. Conclusion. HPV DNA Chip is an accurate method for detecting the 24 HPV genotypes.

Human papillomavirus (HPV) genotyping by HPV DNA chip in cervical cancer and precancerous lesions

The human papillomavirus (HPV) is a well-known cause of cervical cancer. HPV tests are used as an adjunct test to decrease the false-negative rate of cytological screening. However, attempts are being made to replace the cytological screening with HPV tests. Therefore, this study was performed to examine the possibility of using HPV tests as screening test. The results of the tests that were performed at the same time including the ThinPrep cytology, the high-risk group hybrid capture II (HC-II) test, the HPV DNA chip (HD-C) test, and a punch biopsy were compared in 400 women who were referred to us due to abnormal cytology or cervicogram. The accuracy of each test was then evaluated, and the type of virus was investigated using a HD-C test. The positive predictive values detected by the high-risk group HC-II test and HD-C test according to the histological diagnosis outcomes were 56.8 and 53.8%, respectively, for cervicitis; 91.5 and 91.5%, respectively, for cervical intraepithelial neoplasia I (CIN I); 88.1% and 81.0%, respectively, for CIN II; 88.6 and 84.2%, respectively, for CIN III, and 92.5 and 88.7%, respectively, for cancer (in 53 patients). The most prevalent types of HPV according to the HPV tests were types 16, 58, 18, and 52 in which type 16 was detected in the more advanced lesions. The sensitivity was 88.4% for the ThinPrep cytology, 89.9% for the HC-II for the high-risk group, and 86.2% for the HD-C test. These results suggest the possibility of using the HC-II and HD-C tests as screening tests, which have a similar sensitivity as the ThinPrep cytology. Nonetheless, randomized controlled trials will be needed before the actual application of the HPV tests as screening tests. Despite the fact that the importance of HPV type 16 in cancer development was confirmed, the prevalence of types 58 and 52 were relatively high compared with those found in other studies, showing a need for further studies on this subject. These HPV types need to be considered in vaccine development.

Human papillomavirus (HPV) genotyping by HPV DNA chip in cervical cancer and precancerous lesions

ObjectivesThe human papillomavirus (HPV) is a well-known cause of cervical cancer. HPV tests are used as an adjunct test to decrease the false-negative rate of cytological screening. However, attempts are being made to replace the cytological screening with HPV tests. Therefore, this study was performed to examine the possibility of using HPV tests as screening test.Materials and methodsThe results of the tests that were performed at the same time including the ThinPrep cytology, the high-risk group hybrid capture II (HC-II) test, the HPV DNA chip (HD-C) test, and a punch biopsy were compared in 400 women who were referred to us due to abnormal cytology or cervicogram. The accuracy of each test was then evaluated, and the type of virus was investigated using a HD-C test.ResultsThe positive predictive values detected by the high-risk group HC-II test and HD-C test according to the histological diagnosis outcomes were 56.8 and 53.8%, respectively, for cervicitis; 91.5 and 91.5%, respectively, for cervical intraepithelial neoplasia I (CIN I); 88.1% and 81.0%, respectively, for CIN II; 88.6 and 84.2%, respectively, for CIN III, and 92.5 and 88.7%, respectively, for cancer (in 53 patients). The most prevalent types of HPV according to the HPV tests were types 16, 58, 18, and 52 in which type 16 was detected in the more advanced lesions. The sensitivity was 88.4% for the ThinPrep cytology, 89.9% for the HC-II for the high-risk group, and 86.2% for the HD-C test.ConclusionThese results suggest the possibility of using the HC-II and HD-C tests as screening tests, which have a similar sensitivity as the ThinPrep cytology. Nonetheless, randomized controlled trials will be needed before the actual application of the HPV tests as screening tests. Despite the fact that the importance of HPV type 16 in cancer development was confirmed, the prevalence of types 58 and 52 were relatively high compared with those found in other studies, showing a need for further studies on this subject. These HPV types need to be considered in vaccine development.

The efficacy of HPV DNA chip test in the atypical squamous cell of undetermined significance

Objective: This study was performed to investigate the efficacy of DNA chip method for detecting and genotyping of human papillomavirus (HPV) and screening of high-grade CIN (cervical intraepithelial neoplasia) or invasive cancer in the patients with atypical squamous cells of undetermined significance (ASC-US). Methods: This study was based on 131 cases to be revealed ASC-US by Pap smear for the cervical cancer screening from July 2004 to Octorber 2004. They were evaluated by HPV DNA chip test, Cervical colposcopy and directed biopsy, and cone biopsy. The results of type 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 54, 56, 58, 59, 66 and 68 in HPV DNA chip test were categorized as high risk HPV. We evaluate the detection rate of the high-grade CIN and invasive cancer by HPV DNA chip test. Results: The incidence of high risk HPV DNA was 51.1% (67/131). Twelve of 131 (9.2%) were diagnosed as high-grade CIN or CIS on histology. The detection rate of high risk HPV DNA in high-grade CIN and invasive cancer was 83.3% (10/12). The detection rate of high risk HPV DNA was 36.0% (31/86) in normal or reactive, and 83.3% (10/12) in CIN II or above on histology. Higher the grade of biopsy, more the detection rate of high risk HPV DNA by HPV DNA chip test. Conclusion: The use of HPV DNA chip test in patients with ASC-US may be useful in detection of high-grade CIN or invasive cancer.

Detection of Human Papillomavirus in Cervical Neoplasia using HPVDNAChip(R) and Hybrid capture IITM system

Objective : Human Papillomavirus (HPV) is well known as one of the major risk HPVDNAChip factors for cervical cancer. The purpose of this study is to know HPV genotype distribution in women with normal cervix, precancerous lesion, and invasive cervical cancer by HPVDNAChip test. In addition, the result of HPVDNAChip test was compared with Hybrid system for HPV detection. Methods : One hundred forty nine patients were included in this study. 57 women had normal cervix, 59 women had precancerous lesion, and 33 women had invasive cervical cancer. We tested them with two method for detection of Human Papillomavirus (HPV) by HPVDNAChip test and Hybrid system. Hybrid CaptureⅡTM test can detect same high-risk HPVs (16/18/31/33/35/39/45/51/52/56/58/59/68) with HPVDNAChip test which can detect additional 66 & 69 high risk types of HPV. Results : Both methods for the detection of HPV were useful tests. The correlation between the results of two methods was very significant (kappa value 0.721 [p<0.01]). Positive Hybrid test and negative HPVDNAChip test group were 18 women (12.1%) and average Hybrid titer value of this group was 120.7233.0 (meanSD), positive Hybrid test and positive HPVDNAChip test group were 84 women (54.4%) and average titer was 448.1732.8. The Hybrid test showed a sensitivity of 94.6% and a specificity of 78.9% and the HPVDNAChip test showed a sensitivity of 83.7% and a specificity of 89.5%. HPVDNAChip test detected total 14 genotype of HPV. HPV-16 was 28.8% (15/59) in precancerous lesion and 48.5% (19/33) in invasive cancer, most common in both groups. Next common type HPV-58 was 25.4% (12/59) in precancerous lesion and 9.1% (3/33) in invasive cancer. Conclusion : HPVDNAChip test is very sensitive and effective method for detection of Human Papillomavirus (HPV) infection as Hybrid test. In comparison with Hybrid test, HPV genotype and multiple HPV infection information can be given by HPVDNAChip test. Further study will be needed to know the value of screening of cervical cancer by HPVDNAChip test in future.