Thin-layer liquid-based cervical cytology and PCR for detecting and typing human papillomavirus DNA in Flemish women

Depuydt, Christophe; Vereecken, Annie; Salembier, Geert; Vanbrabant, A S; Boels, L A; Herck, E van; Arbyn, Marc; Segers, Kurt; Bogers, Johannes

doi:10.1038/sj.bjc.6600756

Cited by 39 publications

(47 citation statements)

References 36 publications

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“…6,17,[24][25][26] In our study, 26.8% of the screening population were positive for Hr-HPV and 37.1% were positive for any of the 54 HPV types. It seems conceivable that many of the differences observed are attributable to the use of a more sensitive HPV test.…”

Section: Discussionmentioning

confidence: 91%

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Prevalence and viral load of 51 genital human papillomavirus types and three subtypes

Schmitt

Depuydt²,

Benoy³

et al. 2012

Intl Journal of Cancer

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Of the 120 known human papillomaviruses (HPV), 51 HPV types infect the genital mucosa. Very little is known about the prevalence and viral load of the majority of these low-risk (Lr-) HPV types in screening populations. We determined the prevalence of 51 HPV types and three subtypes in 999 consecutive BD-SurePath TM liquid-based cervical cytology samples collected during routine gynecological health checks from Belgian women. This series of screening samples was enriched with ASC-US (n 5 100), low-grade squamous intraepithelial lesion LSIL (n 5 100) and high-grade squamous intraepithelial lesion (HSIL) (n 5 97) and analyzed by BSGP51/61-PCR/MPG assay for 51 HPV types and three subtypes. In consecutive screening samples, any of the 54 genital HPV (sub)types was found in 37.1%; Hr-HPV types were detected more frequently (26.8%) than the 31 Lr-HPV types (16.4%) and the six possibly high-risk types (6.6%). High viral load infections were present in 17.0% of the screening population. Among the women with cytological abnormalities, the prevalence of high viral loads of Hr-HPV types increased from negative for intraepithelial lesion or malignancy (NIL/M) over ASC-US, LSIL to HSIL (5.3, 47.1, 84.2 and 91.8%, respectively). The prevalence of possibly Hr and Lr-HPV types increased from NIL/M to LSIL but declined to HSIL. From NIL/M to HSIL, Hr-HPV infections showed an increasing frequency of high viral loads compared to total DNA positivity, but the increase between LSIL and HSIL was small. Type-specific analyses revealed substantial differences between individual HPV types in these groups. Our study provides quantitative data for the whole spectrum of genital HPV in a Belgian screening population and in a representative set of women with cervical abnormalities.Human papillomaviruses (HPV) are DNA viruses that infect cutaneous and mucosal epithelia. Until now, 120 HPV genotypes are characterized based on sequence information, 1 with evidence for a larger number to exist. There are 51 mucosal HPV types recognized, which are further divided into three groups based on their epidemiological association with cervical cancer (CxCa): 14 high-risk types 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68), six possibly high-risk types 53, 67, 70, 73 and 82) and 31 low-risk types

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Section: Discussionmentioning

confidence: 91%

“…13 Isolation of DNA from cervical cells DNA isolation from standardized liquid-based cytology leftover was performed as described previously. 17,18 The isolated DNA was divided into five aliquots and one aliquot was sent to Heidelberg for HPV genotyping using the BSGP5þ/ 6þ-PCR/MPG assay.…”

Section: Cytologymentioning

confidence: 99%

Prevalence and viral load of 51 genital human papillomavirus types and three subtypes

Schmitt

Depuydt²,

Benoy³

et al. 2012

Intl Journal of Cancer

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“…Cytological results were classified according to the Bethesda system. 22,23 The following classes were distinguished: negative for intraepithelial lesions or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells of undetermined significance, cannot exclude high-grade squamous intraepithelial lesions (ASC-H), low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL).…”

Section: Cervical Cytology and Hpv Testingmentioning

confidence: 99%

“…[18][19][20][21][22][23] The presence of 18 different HPV geno-types was determined using TaqMan (Table 1). 24 The PCR amplifications were performed in a total volume of 5 ll (4 ll master mix and 1 ll DNA) on a LC480 instrument (Roche).…”

Section: Cervical Cytology and Hpv Testingmentioning

confidence: 99%

Type‐specific HPV geno‐typing improves detection of recurrent high‐grade cervical neoplasia after conisation

Heymans

Benoy²,

Poppe

et al. 2011

Intl Journal of Cancer

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The aim of this case-control study was to examine if type-specific human papillomavirus (HPV) DNA geno-typing before and after treatment of high-grade cervical intra-epithelial neoplasia (CIN) improves prediction of recurring or persisting CIN 2 or 3 compared with follow-up cytology or high-risk (hr)HPV testing. Women with biopsy-proven recurrence of CIN 2 or 3 (cases) in a follow-up period of at least 24 months after treatment of high-grade CIN were compared with women without recurrence (controls). These cohorts were identified by a database search of the Riatol Laboratoria (Antwerp, Belgium). In a cohort of 823 women treated with conisation for high-grade CIN between January 2001 and December 2007, 21 patients with a histologically proven recurrence of CIN21 were identified. A group of women (n 5 42) from the same cohort without recurrence was randomly chosen. We found that hrHPV testing at 6 months post-treatment is significantly more sensitive compared with follow-up cytology (ratio: 1.31, 95% confidence interval (CI): 1.10-1.54), but less specific (ratio: 0.85, 95% CI: 0.81-0.90) to predict failure of treatment. When compared with hrHPV testing, HPV geno-typing is more efficient (equal sensitivity, but higher specificity, ratio: 1.43, 95% CI: 1.280-1.62). When compared with follow-up cytology, HPV geno-typing is more sensitive (ratio: 1.31, 95% CI: 1.10-1.54) and more specific (ratio: 1.22, 95% CI: 1.14-1.36). All women who developed a recurrence tested positive for hrHPV. The negative predictive value in the absence of hrHPV DNA was 100%. Six months after treatment HPV genotyping is the most sensitive and specific method to predict recurrent or persistent CIN 2-3 in the next 24 months.There is now overwhelming evidence that a persistent infection with a high-risk human papillomavirus (hrHPV) is the key event in the development of cervical cancer and its precursor lesions, high-grade cervical intra-epithelial neoplasia (CIN 2).1-4 The diagnosis of high-grade CIN 2-3 carries a significant risk of developing invasive carcinoma if it is not detected early and left untreated.5 Conservative treatment with large loop excision of the transformation zone (LLETZ) or conisation is the standard procedure for high-grade CIN and usually results in a complete cure, but residual or recurrent disease still occurs on average in 10% of treated cases. 6 Most treatment failures occur during the first 2 years after surgery. Therefore, according to the current guidelines in most western countries, women who have been treated for CIN2þ, afterward remain under gynaecological surveillance, with cervical smears taken at 6, 12 and 24 months post-treatment.7 Later, they are seen annually until the last two smears read as normal.Various studies have investigated potential predictive factors to identify the women at risk for recurrent disease. These factors include size of the lesion, grade of dysplasia, age, incomplete removal of the lesion and immunosuppressive therapy. 8-11Since persistent cervical infection with hrHPV has been iden...

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“…Until now, 120 HPV genotypes are characterized based on sequence information (1), with evidence for a larger number to exist (2). Currently, there are 51 known mucosal HPV types, which are further divided into three groups based on their epidemiologic association with cervical cancer: high-risk HPV (Hr-HPV: 16,18,31,33,35,39,45,51,52,56,58,59, 66, and 68), possibly high-risk HPV (pHr-HPV: 26, 53, 67, 70, 73, and 82), and low-risk or undefined HPV (Lr-HPV: e.g., 6, 11, 40, 42, 43, and 44; 3). Cervical cancer (CxCa) develops from persistent Hr-HPV infections through precursor lesions, defined histologically as high-grade cervical intraepithelial neoplasia.…”

Section: Introductionmentioning

confidence: 99%

Viral Load of High-Risk Human Papillomaviruses as Reliable Clinical Predictor for the Presence of Cervical Lesions

Schmitt

Depuydt

Benoy

et al. 2013

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Infections with high-risk human papillomaviruses (Hr-HPV) can cause malignant transformation of the human cervical epithelium. HPV DNA tests generally are very sensitive to detect cervical neoplastic lesions but also identify transient HPV infections. As a consequence, the specificity and positive predictive value are low.Methods: We analyzed viral load of Hr-and possibly Hr-HPV types more than seven orders of magnitude (on a log10 scale) in 999 consecutive BD-SurePath liquid-based cervical cytology samples from routine cervical screening enriched with atypical squamous cells of undetermined significance (n ¼ 100), low-grade squamous intraepithelial lesions (LSIL; n ¼ 100), and high-grade squamous intraepithelial lesions (HSIL; n ¼ 97) using type-specific multiplex quantitative real-time PCR and the BSGP5þ/6þ-PCR/MPG assay. In the 36-month follow-up, 79 histologically verified CIN2þ and 797 double-negative cytology cases were identified.Results: Viral loads in LSIL and HSIL were significantly increased compared with no intraepithelial lesion or malignancy in both the quantitative PCR (qPCR) and BSGP5þ/6þ-PCR/MPG assay (P < 0.0001). The mean viral loads in LSIL and HSIL were not significantly different. Using a newly determined high viral load cut off for 14 Hr-HPV types, the sensitivity for prevalent CIN3þ remained at 100% for both assays compared with the minimal detection threshold. The specificity (corresponding to double-negative cytology at subsequent screening episodes) increased substantially (qPCR, from 91.1% to 95.7%; BSGP5þ/6þ-PCR/MPG, from 79.8% to 96.2%).Conclusions: Compared with DNA positivity alone, high Hr-HPV viral loads could reduce the amount of false positive results detected by the BSGP5þ/6þ-PCR/MPG and qPCR by 81.4% and 52.1%, respectively.Impact: Quantitative type-specific HPV DNA assays show high flexibility in defining thresholds that allow optimizing clinical accuracy for cervical cancer precursors. Cancer Epidemiol Biomarkers Prev; 22(3); 406-14. Ó2013 AACR.

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Thin-layer liquid-based cervical cytology and PCR for detecting and typing human papillomavirus DNA in Flemish women

Cited by 39 publications

References 36 publications

Prevalence and viral load of 51 genital human papillomavirus types and three subtypes

Prevalence and viral load of 51 genital human papillomavirus types and three subtypes

Type‐specific HPV geno‐typing improves detection of recurrent high‐grade cervical neoplasia after conisation

Viral Load of High-Risk Human Papillomaviruses as Reliable Clinical Predictor for the Presence of Cervical Lesions

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