HPV genotyping for triage of women with abnormal cervical cancer screening results: a multicenter prospective study

Nakamura, Yuko; Matsumoto, Koji; Nishide, Ken; Nozue, Akiko; Shimabukuro, Koji; Endo, Shigekatsu; Nagai, Kimihiro; Oki, Akinori; Ochi, Hiroki; Morishita, Yukio; Noguchi, Masayuki; Yoshikawa, Hiroyuki

doi:10.1007/s10147-015-0789-4

Cited by 14 publications

(8 citation statements)

References 23 publications

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“…The presence of HPV16/18/52/58 or HPV16/18/31/52/58 was associated with a significantly higher risk for histologic HSIL+ than the absence of these genotypes ( S1 Table ). Using 8 genotypes (HPV16/18/31/33/35/45/52/58) for stratification [ 19 ], the detection of histologic HSIL+ was not improved compared to HPV16/18/31/52/58. A similar finding was observed among 226 women with positive HC2 but negative cytology ( S2 Table ).…”

Section: Resultsmentioning

confidence: 99%

Genotyping for Human Papillomavirus (HPV) 16/18/52/58 Has a Higher Performance than HPV16/18 Genotyping in Triaging Women with Positive High-risk HPV Test in Northern Thailand

et al. 2016

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BackgroundTesting for high-risk human papillomavirus DNA (HPV test) has gained increasing acceptance as an alternative method to cytology in cervical cancer screening. Compared to cytology, HPV test has a higher sensitivity for the detection of histologic high-grade squamous intraepithelial lesion or worse (HSIL+), but this could lead to a large colposcopy burden. Genotyping for HPV16/18 has been recommended in triaging HPV-positive women. This study was aimed to evaluate the screening performance of HPV testing and the role of genotyping triage in Northern Thailand.MethodsA population-based cervical screening program was performed in Chiang Mai (Northern Thailand) using cytology (conventional Pap test) and HPV test (Hybrid Capture 2). Women who had abnormal cytology or were HPV-positive were referred for colposcopy. Cervical samples from these women were genotyped using the Linear Array assay.ResultsOf 5,456 women, 2.0% had abnormal Pap test results and 6.5% tested positive with Hybrid Capture 2. Of 5,433 women eligible for analysis, 355 with any positive test had histologic confirmation and 57 of these had histologic HSIL+. The sensitivity for histologic HSIL+ detection was 64.9% for Pap test and 100% for Hybrid Capture 2, but the ratio of colposcopy per detection of each HSIL+ was more than two-fold higher with Hybrid Capture 2 than Pap test (5.9 versus 2.8). Genotyping results were available in 316 samples. HPV52, HPV16, and HPV58 were the three most common genotypes among women with histologic HSIL+. Performance of genotyping triage using HPV16/18/52/58 was superior to that of HPV16/18, with a higher sensitivity (85.7% versus 28.6%) and negative predictive value (94.2% versus 83.9%).ConclusionsIn Northern Thailand, HPV testing with genotyping triage shows better screening performance than cervical cytology alone. In this region, the addition of genotyping for HPV52/58 to HPV16/18 is deemed necessary in triaging women with positive HPV test.

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Section: Resultsmentioning

confidence: 99%

Genotyping for Human Papillomavirus (HPV) 16/18/52/58 Has a Higher Performance than HPV16/18 Genotyping in Triaging Women with Positive High-risk HPV Test in Northern Thailand

et al. 2016

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“…An overview of study design, population, and test characteristics is provided in the Supplementary Tables 1-2. Additional data was obtained from the authors of most of the studies, with the exception of eight papers that contained all the absolute numbers required for computation of sensitivity and specificity (29,30,37,(47)(48)(49)(50)(51). Study settings included colposcopy clinics (30,32,(34)(35)(36)38,(40)(41)(42)(44)(45)(46)(49)(50)(51), primary screening settings (28,29,39,43,47), a maternity center (31), and pathology archives (33,37).…”

Section: Selection Of Studies Study Characteristicsmentioning

confidence: 99%

Genotyping for Human Papillomavirus Types 16 and 18 in Women With Minor Cervical Lesions

Arbyn

Verdoodt

et al. 2016

Ann Intern Med

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“…Typically, a fraction of the women diagnosed with LSIL or ASCUS lesions may have an underlying CIN grade histopathology or a cervical carcinoma (17, 18). The best management options for such LSIL or ASCUS women are controversial (19, 20). Moreover, a discrete fraction of non-compliant patients drops from any proposed follow-up program (21, 22).…”

Section: Introductionmentioning

confidence: 99%

Over Expressed TKTL1, CIP-2A, and B-MYB Proteins in Uterine Cervix Epithelium Scrapings as Potential Risk Predictive Biomarkers in HR-HPV-Infected LSIL/ASCUS Patients

et al. 2019

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High oncogenic risk human papillomaviruses (HR-HPVs) promote cervical carcinoma development, the fourth most common feminine cancer. A slow oncodevelopmental phase—defined histopathologically as Cervical Intraepithelial Neoplasia (CIN) grades 1–3, or cytologically as Low- or High-grade Squamous Intraepithelial Lesions (LSIL or HSIL)—precedes the malignancy. Cervical carcinoma screenings through HR-HPV genotyping and Pap smears are regularly performed in Western countries. Faulty cytology screening or genotyping or patients' non-compliance with follow-ups can let slip an oncoprogression diagnosis. Novel biomarker tests flanking HR-HPV genotyping and cytology could objectively predict the risk of disease progression thus helping triage LSIL/ASCUS patients. Here, anonymized leftovers of fresh cervical epithelium scrapings from twice (LSIL/ASCUS and HR-HPV DNA)-positive and twice (Pap smear- and HR-HPV DNA)-negative (control) patients in a proteome-preserving solution served to assess the biomarker worth of three cervical carcinoma-related proteins, i.e., B-MYB (or MYBL2), Cancerous Inhibitor of PP2A (CIP-2a), and transketolase-like1 (TKTL1). Leftovers anonymity was strictly kept and storage at −80°C, protein extraction, immunoblotting, and band densitometry were blindly performed. Only after tests completion, the anonymous yet code-corresponding HR-HPV-genotyping and cytology data allowed to assign each sample to the twice-positive or twice-negative group. Descriptive statistics showed that the three proteins levels significantly increased in the twice-positive vs. twice-negative scrapings. Diagnostic ROC curve analysis identified each protein's Optimal Decision Threshold (OTD) showing that TKTL1 and CIP-2a are stronger risk predictive biomarkers (Sensitivity, 0.91–0.93; Specificity, 0.77–0.83) than B-MYB. Logistic Regression coupled with Likelihood-Ratio Tests confirmed that a highly significant relation links increasing TKTL1/CIP-2a/B-MYB protein levels in twice-positive cervical scrapings to the risk of HR-HPV-driven oncoprogression. Finally, a 3 year clinical follow-up showed that 13 patients (50% of total) of the twice-positive group with biomarker values over OTDs compliantly underwent scheduled colposcopy and biopsy. Of these, 11 (i.e., 84.7%) received a positive histological diagnosis, i.e., CIN1 ( n = 5; 38.5%) or CIN2/CIN2+ ( n = 6; 46,2%). Therefore, TKTL1/CIP-2a/B-MYB protein levels could objectively predict oncoprogression risk in twice (HR-HPV- and Pap smear)-positive women. Further studies will assess the translatability of these findings into clinical settings.

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HPV genotyping for triage of women with abnormal cervical cancer screening results: a multicenter prospective study

Cited by 14 publications

References 23 publications

Genotyping for Human Papillomavirus (HPV) 16/18/52/58 Has a Higher Performance than HPV16/18 Genotyping in Triaging Women with Positive High-risk HPV Test in Northern Thailand

Genotyping for Human Papillomavirus (HPV) 16/18/52/58 Has a Higher Performance than HPV16/18 Genotyping in Triaging Women with Positive High-risk HPV Test in Northern Thailand

Genotyping for Human Papillomavirus Types 16 and 18 in Women With Minor Cervical Lesions

Over Expressed TKTL1, CIP-2A, and B-MYB Proteins in Uterine Cervix Epithelium Scrapings as Potential Risk Predictive Biomarkers in HR-HPV-Infected LSIL/ASCUS Patients

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