Characteristics of Apparently False-Negative Digene Hybrid Capture 2 High-Risk HPV DNA Testing

Jastania, Raid A; Geddie, William R.; Chapman, William; Boerner, Scott

doi:10.1309/qejbyt77ymtevj66

Cited by 34 publications

(24 citation statements)

References 10 publications

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“…The majority of the latter lesions shed few abnormal cells, and they are small, as observed in this study, or focal, as reported recently by Jastania et al 19 Presumably, these lesions represent either early or regressing stages of cervical disease, which makes their clinical significance uncertain.…”

Section: Discussionsupporting

confidence: 82%

Significance and possible causes of false-negative results of reflex human papillomavirus infection testing

Eltoum

Chhieng

Crowe

et al. 2007

Cancer

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BACKGROUND. The objective of this study was to assess the rate and possible reasons for false‐negative (FN) reflex human papillomavirus (HPV)‐DNA tests. METHODS. The authors reviewed all ThinPrep cervical specimens that were submitted for reflex HPV‐DNA testing using the Digene Hybrid Capture II (HC2) method from January 2002 to January 2004. Follow‐up biopsies were reviewed. The results were considered HPV‐FN if the HPV‐DNA test was negative and the biopsy was positive for grade ≥2 cervical intraepithelial neoplasia (CIN2+), and the results were considered true positive (HPV‐TP) if the HPV‐DNA test was positive and the biopsy showed CIN2+. HPV‐FN cases were compared with HPV‐TP cases regarding the grade and extent of CIN, the number of abnormal cells on the original ThinPrep slide, and the presence of amplifiable, viral DNA on biopsy. RESULTS. In total, 1520 (66%) of 2309 patients who had diagnoses of atypical squamous cells of undetermined significance (ASCUS) were negative for HPV DNA and 789 patients of 2309 patients (34%) were positive for HPV DNA. Three hundred sixteen women (40%) who had a positive HPV‐DNA test underwent a biopsy. Of those, 36 biopsies (11%) showed CIN2+ (HPV‐TP), and 154 biopsies (66%) showed CIN1. Cervical tissue was available for review from 82 women who had negative HPV‐DNA tests; of these, 6 tissue samples (7%) showed CIN2+ (HPV‐FN), and 13 tissue samples (16%) showed CIN1. Therefore, in the total ASCUS population that was triaged with reflex HPV testing, there were at least 42 women who were diagnosed with CIN2+, for an estimated CIN2+ FN fraction of 14% (6 of 42 women). HPV‐FN lesions were smaller (but the difference was not statistically significant) and shed significantly fewer abnormal cells than HPV‐TP cases. Polymerase chain reaction testing for viral DNA in the biopsy was detected in 3 of 6 women who had HPV‐FN results; none of those positive results demonstrated a viral type that was not included in the Digene probes. CONCLUSIONS. Although the rate of FN high‐grade lesions was significantly higher than that reported in the ASCUS/Low‐grade Squamous Intraepithelial Lesion Triage trial, most missed lesions were small and shed few abnormal cells. It was assumed that those lesions were either in early stages or in regressing stages, which made their clinical significance uncertain. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.

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Section: Discussionsupporting

confidence: 82%

Significance and possible causes of false-negative results of reflex human papillomavirus infection testing

Eltoum

Chhieng

Crowe

et al. 2007

Cancer

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“…Similarly, detection of HPV-35 was somewhat reduced when a mixture of probes for HPV-16, HPV-33 and HPV-35 were used, compared to a single probe for HPV-35. A BARCODE HPV assay has been developed for HPV genotyping, and was evaluated using only six (6,11,16,18, 45 and 51) of 45 different HPV types. (28) A serological multiplex method was reported for the detection of antibodies against HPV proteins based on in situpurified glutathione S-transferase fusion proteins.…”

Section: Discussionmentioning

confidence: 99%

Polymerase chain reaction‐based fluorescent Luminex assay to detect the presence of human papillomavirus types

Oh¹,

Bae

Kim

et al. 2007

Cancer Science

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Becuase 40% of human papillomavirus (HPV) infections are mixed infections, the accurate identification of high-risk HPV genotypes in mixed infections is important for defining a woman's risk for progression to cervical cancer. Thus, advanced Luminex-based HPV genotyping has been developed to simultaneously detect the presence of multiple HPV types. Here, we describe the development of a Luminex-based HPV genotyping that combines polymerase chain reaction amplification with hybridization to fluorescencelabeled polystyrene bead microarrays (Luminex suspension array technology). New HPV type-specific oligonucleotide probes and YBT L1/GP6-1 primers were used to detect the HPV types in 132 clinical samples. We simultaneously evaluated the usefulness of this technique on clinical samples. We detected 15 specific HPV types (6, 16, 18, 31, 35, 42, 51, 52, 55, 56, 58, 59, 66, 67 and 68) examined with specificity without known cross-reaction to other HPV types. The detection limit for the different HPV types was above 500 plasmids. (1) individuals may be infected with more than one type at a time.(2) Because most HPV infections have no visible signs or symptoms, (3) the development of detection tools for HPV identification in asymptomatic patients has been very important. (4) Several HPV DNA detection methods have been described during the last decade, each of which allows the detection of a wide spectrum of HPV types, such as DNA amplification-based methods. Due largely to routine screening using Pap tests, the number of deaths attributed to cervical cancer continues to drop nearly 4% annually. However, the Pap smear has some weaknesses, not least of which is its limited sensitivity for detection of cancer precursors.(5) Therefore, the false-negative rate of the Pap smear ranges from 20 to 30% when cytology is used alone. In addition, there is a false-positive rate of 5-15%.(6 -8) To carry out HPV genotyping, a reliable, FDA-approved test to distinguish the specific HPV types will need to be developed and validated. A DNA-based technology, the Hybrid Capture II HPV test, has been used to detect 13 high-risk types of HPV. (9,10) However, this routine test is not recommended for women under the age of 30 years unless they have atypical or equivocal Pap test results. In addition, despite its high sensitivity, false-negative results are known to occur for histologically confirmed cervical intraepithelial neoplasia (CIN)2 or CIN3 cases, with its impossibility to perform genotyping. (11,12) Therefore, the current techniques available for detection of HPV types all have shown limited ability for complete detection; there is no single technique that provides complete detection to date. Therefore, a new and improved HPV assay that is highly sensitive and reproducible is required. Multiplex technology is a new method that is based on fluorescent bead technology, and allows simultaneous detection of nucleic acids against up to 100 different HPV types. (13,14) Recently, this technology has been used for the genotyping of HPV types u...

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“…It is also likely that primary human papillomavirus screening would have detected most, but not all, of these lesions. 27 More than half of the interval cancers in our series had other factors in the histories, often in addition to negative cytology. Low-grade cytology had rarely been managed as recommended and none of the cancers were in women with low-grade cytology followed by two or three negative tests.…”

Section: Discussionmentioning

confidence: 74%

Invasive cervical cancer audit: why cancers developed in a high‐risk population with an organised screening programme

Herbert

Anshu

Culora

et al. 2010

BJOG

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Objectives To investigate why invasive cervical cancers developed in a high-risk urban population with an established screening programme and to place cancers in the context of high-grade cervical intraepithelial neoplasia (CIN) and cervical glandular intraepithelial neoplasia (CGIN) diagnosed during the same period of time. Results There were 133 invasive cancers, 53 CGIN, 1502 CIN3 and 1472 CIN2. Screen-detected cancers in asymptomatic women comprised 48.9% of cancers and were successively more likely to be in younger age groups (P = 0.03); all except one were stage IA or IB1. Screen-detected IA cancers were more likely (P < 0.001) to be in women screened within 0.5-5.0 years (80.5%) than screendetected fully invasive (58.3%) or symptomatic cancers (35.3%). Seventy-one (53.4%) women had been screened within 0.5-5.0 years; 11 had negative cytology within 0.5-3.5 years and two tests within 10 years. The other 60 had negative tests less frequently or had previous abnormal cytology, colposcopy or treatment. Potentially avoidable factors were often multiple, including false-negative cytology, high-grade cytology reported as low-grade and lapses in attendance either for routine or repeat screening, or for colposcopy or treatment.Conclusion While often potentially avoidable, cancers in previously screened women tended to be early stage, detected by cytology and rare when compared with high-grade CIN.

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Characteristics of Apparently False-Negative Digene Hybrid Capture 2 High-Risk HPV DNA Testing

Cited by 34 publications

References 10 publications

Significance and possible causes of false-negative results of reflex human papillomavirus infection testing

Significance and possible causes of false-negative results of reflex human papillomavirus infection testing

Polymerase chain reaction‐based fluorescent Luminex assay to detect the presence of human papillomavirus types

Invasive cervical cancer audit: why cancers developed in a high‐risk population with an organised screening programme

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