Use of semi-quantitative PCR for human papillomavirus DNA type 16 to identify women with high grade cervical disease in a population presenting with a mildly dyskaryotic smear report

Pj, Bavin; Giles, John; Deery, Alastair R.S.; Crow, Julie; Pd, Griffiths; Emery, Vincent C.; Pg, Walker

doi:10.1038/bjc.1993.110

Cited by 78 publications

(58 citation statements)

References 12 publications

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“…The results were similar for all grades of cytological referral, suggesting that they may also be applicable to women with a single mildly dyskaryotic smear, and that a high level of HPV 16 in the presence of any degree of dyskaryosis is grounds for immediate referral for colposcopy. Recent results from Bavin et al (1993) also support this view. However, the lack of high levels of HPV 16 did not indicate the absence of high-grade disease, since this was found in about 40% of the CIN III patients.…”

supporting

confidence: 71%

Type-specific human papillomavirus DNA in abnormal smears as a predictor of high-grade cervical intraepithelial neoplasia

Cuzick

Terry²,

Ho³

et al. 1994

Br J Cancer

202

132

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Summary Human papillomavirus (HPV) typing and quantitation by polymerase chain reaction was performed on exfoliated cells from 133 women referred for colposcopy because of an abnormal smear. High levels of HPV 16 correctly predicted cervical intraepithelial neoplasia (CIN) grade II-III in 93% of its occurrences, but only 59% of cases of CIN III were associated with high levels of this type. Eighty-four per cent of CIN III lesions contained high levels of at least one of HPV types 16, 18, 31, 33 and 35, but the other types were less specific for CIN III than HPV 16. Overall HPV testing compared favourably with cytology for predicting high-grade CIN lesions, but it would appear that some combination of the two modalities will produce better performance than either alone. In particular, HPV testing appears to be helpful in determining which women with mildly abnormal smears have high-grade underlying lesions in need of immediate referral for colposcopy.Cytological screening for cervical dysplasia is an effective method of reducing the incidence of and mortality from cervix cancer (Hakama, 1982; IARC Working Group, 1986;Laara et al., 1987;Hakama et al., 1991 (Barton et al., 1989;Szarewski et al., 1991). Possibly these can be safely left until the next routine smear, but invasive cancer can also be missed (Mitchell et al., 1990). Lastly, on the scale practised today, cytological examination of slides for dyskaryotic changes is a time-consuming, tedious and eye-fatiguing activity leading to difficulty in recruiting and keeping staff, and making the cost-effectiveness of the programme less favourable than it might be.In the past two decades much effort has been devoted towards trying to automate and simplify the preparation and reading of smears, and several prototype computer-assisted screening systems are under evaluation (Banda-Gamboa et al., 1992). However, none is currently in routine use, and interest in alternative or complementary modalities is high. The most thoroughly evaluated among these is cervicography (Stafl, 1981;Tawa et al., 1988;Szarewski et al., 1991), which is highly sensitive but does not appear to be sufficiently specific. However, the possibility that has stimulated the most interst is the detection and typing of HPV DNA in exfoliated cervical cells Schiffman et al., 1991;van den Brule et al., 1991;Koutsky et al., 1992 In this paper we extend that report by increasing the number of women studied and by looking individually at several HPV types. The specific aim was to examine the value of HPV typing for deciding which women with mild cervical abnormalities detected by cytology actually harbour a highgrade (CIN II/III) lesion and are in need of immediate referral for colposcopy. We also wished to examine the relative value of the different HPV types in predicing high-grade disease. The use of HPV DNA detection, typing and quantification in primary screening will not be addressed here and is the subject of several large ongoing studies. Patients and methodsPatients referred for colposcopy were stu...

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supporting

confidence: 71%

Type-specific human papillomavirus DNA in abnormal smears as a predictor of high-grade cervical intraepithelial neoplasia

Cuzick

Terry²,

Ho³

et al. 1994

Br J Cancer

202

132

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“…6 In this context, it has been demonstrated for HPV 16 infections that increased viral loads would be associated with an increased risk of CIN 2 whereas reduced amounts of viral DNA reflects the absence of CIN lesions or viral clearance, which is associated with regression of CIN lesions. 7 Still, data in favor of viral load being informative for risk of CIN 2 are mainly based on HPV 16, whereas those of hrHPV types other than HPV 16 are limited and inconsistent, [8][9][10][11][12][13][14][15][16][17][18][19] obviously because of the generally low numbers of women with non-HPV 16 types studied so far. Moreover, the potential value of viral load assessment is quite likely to be dependent on the method used to define HPV positivity since its impact seems lower when the hybridization-based hybrid capture 2 (hc2) is used to define HPV positivity when compared with PCR-based assays, which generally display a higher analytical sensitivity.…”

mentioning

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

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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...

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“…Such a policy, however, results in a high rate of colposcopic and reconisation referrals and, consequently, a Previous studies on the relation between the HPV load and the histologic grade of cervical lesions have yielded controversial results. Several investigations in which a semiquantitative PCR was used showed a significant correlation between cytological grade and the amount of HPV-16 DNA in cervical samples (Cuzick et al, 1992(Cuzick et al, , 1994Bavin et al, 1993). In contrast, two other studies using Hybrid Capture assays revealed smaller amounts of viral DNA in cervical samples of women with HSIL compared to those with LSIL (Farthing et al, 1994;Sun et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies using the semiquantitative polymerase chain reaction analysis (PCR) have shown a correlation between HSIL and a large amount of HPV-16 DNA in cervical samples and a small amount in samples of a low-grade squamous intraepithelial lesion (LSIL) (Cuzick et al, 1992(Cuzick et al, , 1994Bavin et al, 1993). In contrast, two other studies using a Hybrid Capture assay revealed smaller amounts of viral DNA in the cervical samples of women with HSIL compared with LSIL (Farthing et al, 1994;Sun et al, 1995).…”

mentioning

confidence: 99%

Clinical and economic benefit of HPV-load testing in follow-up and management of women postcone biopsy for CIN2–3

et al. 2003

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This study aimed to evaluate the clinical and economic implications of integrating human papilloma virus (HPV) load testing into the follow-up and management protocol of women postconisation for high-grade cervical intraepithelial neoplasia (CIN2 -3). We evaluated 130 suitable women: 63 were screened biannually by Pap smears ('conventional approach') and 67 also had HPV-load testing ('HPV approach'). More stringent criteria for undergoing colposcopy or reconisation were observed by the former group compared to the latter. Both approaches were analysed for cost effectiveness. There were 33 out of 67 (49.2%) colposcopic referrals and 24 out of 67 (35.8%) reconisation/hysterectomies with the 'conventional approach' compared to 9 out of 63 (14.2%) and 7 out of 63 (11.1%) with the 'HPV approach'. Cervical intraepithelial neoplasia 2 -3 residual disease was detected in 7 out of 67 (10.5%) and 7 out of 63 (11.1%) women. The 'conventional approach' had more negative colposcopic biopsies and more negative reconisation/hysterectomy histologies than the 'HPV approach'. The respective cost per detection of one case of residual disease was US$3573 and US$3485. The 'HPV approach' required fewer colposcopic and reconisation procedures to detect one case of residual CIN2 -3. Its higher positive predictive value than that of cytology provided a significant decrease in false positive rates and a reduction of US$88 per detected case.

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Use of semi-quantitative PCR for human papillomavirus DNA type 16 to identify women with high grade cervical disease in a population presenting with a mildly dyskaryotic smear report

Cited by 78 publications

References 12 publications

Type-specific human papillomavirus DNA in abnormal smears as a predictor of high-grade cervical intraepithelial neoplasia

Type-specific human papillomavirus DNA in abnormal smears as a predictor of high-grade cervical intraepithelial neoplasia

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

Clinical and economic benefit of HPV-load testing in follow-up and management of women postcone biopsy for CIN2–3

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