Distribution and viral load of eight oncogenic types of human papillomavirus (HPV) and HPV 16 integration status in cervical intraepithelial neoplasia and carcinoma

Guo, Ming; Sneige, Nour; Silva, Elvio G.; Jan, Yee Jee; Cogdell, David; Lin, E.; Luthra, Rajyalakshmi; Zhang, Wei

doi:10.1038/modpathol.3800737

Cited by 58 publications

(59 citation statements)

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“…Inform HPV III probe sets able to detect 13 types of oncogenic HPV (i.e., types 16,18,31,33,35,45, 51, 52, 56, 58, 59, 68, and 70) were provided by Ventana Medical Systems. The ISH assay was performed according to the manufacturer's guidelines using the BenchMark automated slide staining system (Ventana Medical System).…”

Section: Thementioning

confidence: 99%

Evaluation of a Commercialized In Situ Hybridization Assay for Detecting Human Papillomavirus DNA in Tissue Specimens from Patients with Cervical Intraepithelial Neoplasia and Cervical Carcinoma

Guo¹,

Gong²,

Deavers³

et al. 2008

J Clin Microbiol

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To evaluate a commercialized in situ hybridization (ISH) assay for detecting human papillomavirus (HPV) DNA, we compared the ability of a new ISH probe, Inform HPV III (Ventana Medical Systems, Tucson, AZ), to that of PCR assays to detect HPV DNA in cervical tissue specimens with normal cervix (20 cases), cervical intraepithelial neoplasia (CIN; CIN 1, 27 cases; CIN 2, 28 cases; and CIN 3, 33 cases), and cervical carcinoma (29 cases). General HPV DNA was detected using consensus primer-mediated PCR assays. HPV genotyping was performed by using EasyChip HPV blot (King Car Yuan Shan Institute, I-Lan, Taiwan). HPV16 integration status (E2/E6 ratio) was determined by using quantitative real-time PCR. Our findings showed that the ISH and PCR had fair to good agreements in detecting HPV DNA across all CIN categories without significant differences (Kappa coefficient, 0.34 to 0.63; P ‫؍‬ 0.13 to 1.0). However, ISH detected significantly fewer HPV-positive cases in carcinoma than PCR did (Kappa coefficient, 0.2; P ‫؍‬ 0.03). Eleven cases with ISH ؊ PCR؉ results had HPV types that can be detected by Inform HPV III. Five carcinoma cases with ISH ؊ PCR ؉ results showed a significantly higher level of integrated HPV16 (P ‫؍‬ 0.008) than did the ISH ؉ cases. As a consequence, lower copy numbers of episomal HPV16 in carcinoma might be the cause for the false-negative ISH results. Although the punctate signal pattern of HPV significantly increased with the severity of disease (P trend ‫؍‬ 0.01), no significant difference in the HPV16 integration status was observed between the cases with a punctate signal only and the cases with mixed punctate and diffuse signals (P ‫؍‬ 0.4). In conclusion, ISH using the Inform HPV III probe seems comparable to PCR for detecting HPV DNA in cervical tissue with CINs. False-negative ISH results appear to be associated with the lower copy numbers of the episomal HPV16 but not with the ability of the Inform HPV III probe to detect specific HPV types. In addition, signal patterns, especially a mixed punctate and diffuse pattern of HPV, cannot be reliably used to predict viral integration status.

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Section: Thementioning

confidence: 99%

Evaluation of a Commercialized In Situ Hybridization Assay for Detecting Human Papillomavirus DNA in Tissue Specimens from Patients with Cervical Intraepithelial Neoplasia and Cervical Carcinoma

Guo¹,

Gong²,

Deavers³

et al. 2008

J Clin Microbiol

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“…Epidemiology studies and our previous observations in cervical tissue specimens demonstrated that the eight major oncogenic HPV types, HPV16, 18, 31, 33, 35, 45, 52 and 58, are closely associated with CIN 2/3 and cervical carcinoma, collectively accounting for more than 80% of cervical carcinoma and CIN 2/3. [10][11][12] Of these eight types, HPV16 and 18 are the most clinically relevant HPV types. 10,21 In our study using Pap cytology specimens, we confirmed that HPV16 and 18 had the highest association with CIN 2/3/carcinoma in women with LSIL or ASCUS.…”

Section: Discussionmentioning

confidence: 99%

“…15 HPV DNA was determined using consensus primer-mediated PCR assays as described previously. 12 Briefly, b-globin (268 bp) was amplified to determine the quality of the extracted DNA using primer sets pc04/gh20 according to Bauer et al 16 and using AmpliTaq Gold polymerase (Applied Biosystems, Foster City, CA, USA). A 25-ng aliquot of genomic DNA was added to a PCR master mixture containing 1 Â PCR buffer (100 mM Tris-HCl, 500 mM KCl, pH 8.3), 200 mM concentrations of each deoxynucleoside triphosphate, 200 nM primer, 1.5 mM MgCl 2 , and 2.5 units of AmpliTaq Gold DNA polymerase.…”

Section: Hpv Dna Testing Using Consensus Primer-mediated Pcrmentioning

confidence: 99%

“…10 In cervical tissue specimens, we also confirmed that these eight oncogenic HPV types were significantly associated with CIN 2/3/carcinoma, whereas the other HPV types were not. 12 Detecting the oncogenic HPV types with statistically higher associations with CIN 2/3/carcinoma and persistency could be clinically more relevant in predicting CIN 2/3 or CIN progression, 13 and may improve specificity and PPV of HPV DNA testing.…”

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confidence: 99%

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Human papillomavirus genotyping for the eight oncogenic types can improve specificity of HPV testing in women with mildly abnormal Pap results

et al. 2008

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To evaluate whether human papillomavirus (HPV) genotyping for the selected oncogenic HPV types can improve the efficacy of HPV DNA testing in predicting cervical intraepithelial neoplasia (CIN 2/3) in women with mildly abnormal Pap results, we compared HPV DNA testing and HPV genotyping for eight oncogenic types (16, 18, 31, 33, 35, 45, 52 and 58) in Pap specimens with abnormal results (HSIL, 20 cases; LSIL, 42 cases; ASC-US, 94 cases) and follow-up biopsies. Using consensus primer-mediated PCR assays, HPV DNA was detected in 90% (18/20) of HSIL, 95% (40/42) of LSIL and 64% (60/94) of ASC-US cases. HPV DNA positivity was significantly associated with CIN 2/3/carcinoma (Po0.001) in women with ASC-US, but not in women with LSIL (P ¼ 0.52). Of HPV DNA-positive specimens, the eight oncogenic HPV types were detected in 83% of HSIL cases (15/18), 53% of LSIL cases (21/40), and 47% of ASC-US cases (28/60). The eight oncogenic HPV types were significantly associated with CIN 2/3/carcinoma (OR, 10.6; 95% CI, 3.98-28.10; Po0.001), whereas no significant association was observed between the non-eight oncogenic HPV types and CIN 2/3/carcinoma (OR, 2.20; 95%CI, 0.80-6.03; P ¼ 0.125). In women with ASC-US, HPV genotyping for the eight oncogenic types showed higher specificity (81 vs 46%) and positive predictive value (PPV, 44 vs 26%) in predicting CIN 2/3/carcinoma compared to HPV DNA testing. Similarly, in women with LSIL, higher specificity (69 vs 8%) and PPV (62 vs 39%) for predicting CIN 2/3/carcinoma were also observed using HPV genotyping test for the eight oncogenic types compared to HPV DNA testing. Our findings suggested that HPV genotyping for the eight oncogenic types might be useful to improve the efficacy of HPV DNA testing for predicting CIN 2/3/carcinoma in women with mildly abnormal Pap results, which may lead to personalized clinical management with improved patient compliance for follow-up. Modern Pathology (2008Pathology ( ) 21, 1037Pathology ( -1043 doi:10.1038/modpathol.2008 published online 23 May 2008 Keywords: human papillomavirus; HPV; genotyping; HSIL; LSIL; ASCUS Oncogenic HPV infection has been recognized as a primary risk factor responsible for more than 99% of cervical carcinoma and high-grade cervical precancerous lesions, that is, CIN 2/3.1 Persistent oncogenic HPV infection has been considered as the most important factor to determine cervical precancerous lesion progression. 2,3 In the United States, HPV DNA testing in conjunction with Pap cytology test has become standard practice for patient management in gynecology clinics and cervical cancer prevention programs. 4,5 Reflex oncogenic HPV DNA testing using pooled-probes has proved cost effective in the triage of women with atypical squamous cells of under-determined significance (ASC-US).6 Triage of women with low-grade squamous intraepithelial lesions (LSIL) using HPV DNA testing was recently recommended, but only for postmenopausal women. 4 The reason that HPV DNA testing was not recommended initially in the triage of women with LSIL...

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“…For now, it remains largely unclear whether the measurement of HPV integration status could be a useful biomarker for progressive disease. Several studies suggest that identification of integrated viral forms could support HPVbased screening and triage strategies (2,(69)(70)(71)(72)(73)(74)(75).…”

Section: Hpv Analysis: Possibilities and Methodsmentioning

confidence: 99%

Human Papillomavirus in Cervical Cancer Screening: Important Role as Biomarker

Boulet

Horvath

Berghmans³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Cervical cytology screening has reduced cervical cancer morbidity and mortality but shows important shortcomings in terms of sensitivity and specificity. Infection with distinct types of human papillomavirus (HPV) is the primary etiologic factor in cervical carcinogenesis. This causal relationship has been exploited for the development of molecular technologies for viral detection to overcome limitations linked to cytologic cervical screening. HPV testing has been suggested for primary screening, triage of equivocal Pap smears or low-grade lesions and follow-up after treatment for cervical intraepithelial neoplasia. Determination of HPV genotype, viral load, integration status and RNA expression could further improve the effectiveness of HPV-based screening and triage strategies. The prospect of prophylactic HPV vaccination stresses the importance of modification of the current cytology-based screening approach.

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Distribution and viral load of eight oncogenic types of human papillomavirus (HPV) and HPV 16 integration status in cervical intraepithelial neoplasia and carcinoma

Cited by 58 publications

References 57 publications

Evaluation of a Commercialized In Situ Hybridization Assay for Detecting Human Papillomavirus DNA in Tissue Specimens from Patients with Cervical Intraepithelial Neoplasia and Cervical Carcinoma

Evaluation of a Commercialized In Situ Hybridization Assay for Detecting Human Papillomavirus DNA in Tissue Specimens from Patients with Cervical Intraepithelial Neoplasia and Cervical Carcinoma

Human papillomavirus genotyping for the eight oncogenic types can improve specificity of HPV testing in women with mildly abnormal Pap results

Human Papillomavirus in Cervical Cancer Screening: Important Role as Biomarker

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