Triage using HPV‐testing in persistent borderline and mildly dyskaryotic smears: Proposal for new guidelines

Bais, Aagje G.; Rebolj, Matejka; Snijders, Peter J.F.; Schipper, Frits A. de; Meulen, Dries A.J. van der; Verheijen, René H.M.; Voorhorst, Feja J.; Ballegooijen, Marjolein van; Meijer, Chris J.L.M.; Helmerhorst, Theo J.M.

doi:10.1002/ijc.20958

Cited by 36 publications

(42 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Delayed HPV DNA testing has been considered safe (4,6), but this conclusion is based on small studies. In our study, three cervical carcinomas were detected, all of which had normal cytological results up to 15 years before invitation to our study, the criterion for which was screening-detected ASCUS/LSIL cytology.…”

Section: Discussionmentioning

confidence: 99%

Cytology and Human Papillomavirus Testing 6 to 12 Months after ASCUS or LSIL Cytology in Organized Screening To Predict High-Grade Cervical Neoplasia between Screening Rounds

et al. 2012

View full text Add to dashboard Cite

We carried out a prospective study comparing the performance of human papillomavirus (HPV) E6/E7 mRNA (PreTect HPVProofer; NorChip, Klokkarstua, Norway) and DNA (Amplicor HPV test; Roche Diagnostics, Basel, Switzerland) triage testing of women 6 to 12 months after atypical-squamous-cells-of-undetermined-significance (ASCUS) or low-grade-squamous-intraepithelial-lesion (LSIL) cytology in organized screening to predict high-grade cervical intraepithelial neoplasia of grade 2 or worse (CIN2؉) between screening rounds. Between January 2005 and April 2008, 692 study women with screening-detected ASCUS/ LSIL cytology 6 to 12 months earlier returned for HPV mRNA and DNA testing and repeat cytology. The median follow-up time was 3 years, using existing health care facilities. Follow-up test results were available for 625 women. Of the 145 CIN2؉ cases detected during the study period, 95 (65.5%) were HPV mRNA positive 6 to 12 months after screening-detected ASCUS/LSIL, 44 (30.4%) were HPV mRNA negative, and 6 (4.1%) were invalid. The corresponding HPV DNA results were 139 (95.9%), 5 (3.4%), and 1 (0.7%), respectively. The cumulative incidences of CIN2؉ 3 years after a negative HPV mRNA and DNA test were 10.3% (95% confidence interval [CI], 7.2 to 13.3%) and 1.8% (95% CI, 0.0 to 3.6%), respectively. The cumulative incidences of CIN2؉ 3 years after positive HPV mRNA and DNA tests were 52.8% (95% CI, 40.1 to 60.1%) and 41.3% (95% CI, 35.5 to 46.6%), respectively. In conclusion, both positive HPV mRNA and DNA test results have a high enough long-term prediction of CIN2؉ risk to consider referral to colposcopy as good practice when performed in delayed triage of women with ASCUS/LSIL cytology. In addition, the low CIN2؉ risk among women with a negative Amplicor HPV test in our study confirms its safe use in a clinical setting. The 2-year cumulative risk of invasive cervical cancer for women with cytological results of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) has been reported to be in the range of 0.10% to 0.25% (20). High-risk human papillomavirus (HPV) is recognized as the main cause of cervical cancer (40), and HPV DNA testing in the follow-up of women with ASCUS/LSIL cytology has proven to be a very sensitive method to further identify those at increased risk of cervical cancer, albeit at the cost of low specificity (3). Immediate high-risk HPV DNA testing (i.e., reflex testing) has proven useful in identifying women with ASCUS cytology who should be referred promptly to colposcopy. However, application of reflex testing among women with LSIL cytology is disputed, as three of four women generally test positive for highrisk HPV DNA (3, 15).European guidelines for quality assurance in cervical cancer screening recommend several different follow-up algorithms for women with ASCUS and LSIL cytology, but there is no consensus on the use of any one algorithm for a given cytological diagnosis. The guidelines recommend that women with LSIL or ASCUS be referre...

show abstract

Section: Discussionmentioning

confidence: 99%

Cytology and Human Papillomavirus Testing 6 to 12 Months after ASCUS or LSIL Cytology in Organized Screening To Predict High-Grade Cervical Neoplasia between Screening Rounds

et al. 2012

View full text Add to dashboard Cite

show abstract

“…women with BMD). 31,32 Remaining hrHPV positive women with normal cytology who are positive for HPV 16, 18, 31 and/or 33 are subjected to type-specific real-time PCR for viral load analysis. Those with HPV 16, 18, 31 and/or 33 viral load values above the mentioned 33rd percentile thresholds could then be subjected to a more aggressive management, i.e.…”

Section: Discussionmentioning

confidence: 99%

Determination of viral load thresholds in cervical scrapings to rule out CIN 3 in HPV 16, 18, 31 and 33‐positive women with normal cytology

Snijders

Hogewoning

Hesselink

et al. 2006

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

An increased high-risk human papillomavirus (hrHPV) viral load in cervical scrapings has been proposed as a determinant for highgrade cervical intraepithelial neoplasia (CIN) and cervical cancer ( CIN 2), but data so far for HPV types different from HPV 16 are limited and inconsistent. In addition, a viral load threshold to distinguish hrHPV positive women without CIN 2 still has not been defined. Here, we used baseline cervical scrapings of women with normal cytology participating in a large population-based cervical screening trial (i.e. POBASCAM) who were GP51/61-PCR positive for 4 common hrHPV types, i.e. HPV 16, 18, 31 or 33, as a reference to arbitrarily define various viral load thresholds (i.e. 25th, 33rd, 50th, 67th and 75th percentiles of the lowest viral load values) for distinguishing women having single infections with these types without high-grade CIN. Viral load assessment was performed by real time type-specific PCR. The viral load threshold values were subsequently validated on abnormal cervical scrapes of 162 women with underlying, histologically confirmed CIN lesions containing 1 of these 4 hrHPV types. All 59 women with CIN 3 had viral load levels that were higher than those of 33% of the women with normal cytology containing the respective hrHPV type detectable by GP51/61-PCR (i.e. higher than the 33rd percentile of viral load). By using this 33rd percentile viral load cut-off, sensitivity for CIN 3 of 100% (95% CI 93.9-100) was obtained. Hence, application of this viral load threshold would increase the specificity of HPV testing for HPV 16, 18, 31 and 33-associated prevalent CIN 3 without the cost of a marked reduction in sensitivity. In practice, on the basis of viral load analysis, a less aggressive management can be foreseen for 33% of the women with normal cytology participating in a population-based screening program who are GP51/61-PCR positive for HPV 16, 18, 31 or 33. ' 2006 Wiley-Liss, Inc. Key words: HPV; viral load; CIN; real time PCRThe relationship between high-risk human papillomavirus (hrHPV) infection and cervical cancer has become evident from epidemiological and functional studies. 1-3 hrHPV DNA has been detected in almost all cervical squamous cell carcinomas and adenocarcinomas. This finding has led to the widely accepted concept that hrHPV infection is a necessary cause of cervical cancer. [1][2][3] The close association between hrHPV and cervical cancer has resulted in the use of hrHPV testing on cervical scrapes for the detection of cervical cancer and its precursor stages. Several studies have shown that addition of hrHPV testing to cervical cytology improves the sensitivity and negative predictive value for highgrade cervical intraepithelial neoplasia (CIN) and cervical cancer ( CIN 2) compared with cytology alone. 4,5 However, the positive predictive value of the hrHPV test is relatively low because many hrHPV positive women will clear the virus. Especially, hrHPV positive women with cytomorphologically normal smears fall in this category. As a consequence, seve...

show abstract

“…One case of high-grade CIN in an HPV-negative woman was found, but further follow-up with final colposcopy after 1 year did not identify other cases (cumulative sensitivity of 50/51 = 98%). 12 …”

Section: Longitudinal Findingsmentioning

confidence: 99%

Human papillomavirus‐based triage of women showing a cervical cytology result of borderline or mild dyskaryosis

Arbyn

Martin‐Hirsch

Wentzensen

2010

BJOG

View full text Add to dashboard Cite

show abstract

Triage using HPV‐testing in persistent borderline and mildly dyskaryotic smears: Proposal for new guidelines

Cited by 36 publications

References 43 publications

Cytology and Human Papillomavirus Testing 6 to 12 Months after ASCUS or LSIL Cytology in Organized Screening To Predict High-Grade Cervical Neoplasia between Screening Rounds

Cytology and Human Papillomavirus Testing 6 to 12 Months after ASCUS or LSIL Cytology in Organized Screening To Predict High-Grade Cervical Neoplasia between Screening Rounds

Determination of viral load thresholds in cervical scrapings to rule out CIN 3 in HPV 16, 18, 31 and 33‐positive women with normal cytology

Human papillomavirus‐based triage of women showing a cervical cytology result of borderline or mild dyskaryosis

Contact Info

Product

Resources

About