Hpv Viruses - Hpv and Cervical Dysplasia

Lie AK, Risberg B, Borge B, Sandstad B, Delabie J, Rimala R, Onsrud M, Thoresen S. Department of Pathology, The Norwegian Radium Hospital, Oslo, Norway.

OBJECTIVE.: To compare DNA-based and mRNA-based methods for detection of high-grade cervical neoplasia in Norway. METHODS.: HPV prevalence was analyzed in 383 women with positive index cytology, selected from gynecology clinics. All patients were investigated by a new PAP smear, histology, and two commercially available HPV tests: Hybrid Capture II (Digene, Gaithersburg, MD) and the Pre Tect HPV-Proofer (NorChip AS). Cases with positive DNA test and negative mRNA test and cases with high-grade histology and negative HPV tests were retested with PCR and sequencing. We regarded the infection as latent or transient if sequencing revealed an HPV type included in both assays. RESULTS.: High-risk HPV was detected in 99.7% of the histological confirmed high-grade lesions (CIN2+) (290/291). The DNA test was positive in 95% (275/291), and the mRNA test was positive in 77% (225/291) of the histological confirmed high-grade lesions. All invasive carcinomas were mRNA positive. The DNA test was significantly more often positive in benign and low-grade lesions, some of which were found to be false positive due to cross-contamination with unrelated types. High-grade histology was detected in 83% of women with normal cytology and positive mRNA test. Latent or transient infections were detected in 11 low-grade and 12 high-grade preinvasive lesions. Sequencing revealed high-risk HPV types included only in the DNA test in 35 high-grade preinvasive lesions, HPV 52 and 58 were the most prevalent HPV types. CONCLUSIONS.: These HPV tests have the potential to improve the detection rate of high-grade cervical neoplasia, with some limitations. The mRNA test seems to be more appropriate for risk-evaluation. Larger scale, population based studies are necessary to evaluate the predictive values of HPV testing in Norway.

Ginekol Pol. 2004 Oct;75(10):807-13.

Controversies in the Bethesda System. To diagnose atypical squamous cells of undetermined significance (ASCUS) or not to diagnose?

Hpv Virus - Article in Polish

The classification of pap smears according to the Bethesda System introduced to the cytologic diagnostics atypical squamous cells of undetermined significance (ASCUS). From the moment of the introduction this term arises many controversies because morphological criteria proposed for the determining ASCUS are very subjective. Even most experienced cytologists not always are able to correct diagnosis of ASCUS. There are also doubts in the clinical procedure connected with the recognition ASCUS. To diminish doubts to the minimum appeared several proposals categorization of ASCUS. The cytologic diagnosis of ASCUS is a serious dilemma both clinical and considerable economic problem. There are suggestions of the elimination from the Bethesda System recognition ASCUS. Many authors it maintains that there is no reason to qualify atypical cells as ASCUS because it can be an image of the occurrence cervical intraepithelial neoplasia (CIN). The hope is that the three-dimensional microscopy, HPV DNA testing, cellular biomarkers, involvement of the cytology to colposcopic research considerably will decrease the number of incorrect diagnoses of ASCUS with the advantage for the clinical procedure. In light of opinions introduced in this paper it appears that the diagnostics ASCUS is legitimate. It is necessary to perform precise microscopic analysis of morphology observed cellules. The recognition of ASCUS one ought to place only exceptionally remembering simultaneously about clinical consequences of such diagnosis.

Publication Types:
• Review
• Review, Tutorial

Obstet Gynecol Surv. 2004 Jul;59(7):543-53.

HPV testing and monitoring of women after treatment of CIN 3: review of the literature and meta-analysis.

Zielinski GD, Bais AG, Helmerhorst TJ, Verheijen RH, de Schipper FA, Snijders PJ, Voorhorst FJ, van Kemenade FJ, Rozendaal L, Meijer CJ. The Department of Pathology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.

According to the current guidelines in most western countries, women treated for cervical intraepithelial neoplasia grade 3 (CIN 3) are followed for at least 2 years after treatment by cytology.High-risk human papillomavirus (hrHPV) infections are necessary for the development and maintenance of CIN 3. HrHPV testing could be used to improve monitoring of women treated for CIN 3. This has prompted numerous studies for the implementation of hrHPV testing in monitoring of women treated for CIN 3. Included in this review are 20 studies, published between 1996 and 2003, comparing hrHPV testing with either resection margins or cervical cytology to predict recurrent/residual disease, and 11 of them could be used in a meta-analysis.In the meta-analysis of the 11 studies, the negative predictive value (NPV) for recurrent/residual disease of hrHPV testing was 98% (95% CI 97-99%), that of resection margins 91% (95% CI 87-94%), and that of cervical cytology 93% (95% CI 90-95%). When hrHPV testing was performed in conjunction with cytology, the sensitivity was 96% (95% CI 89-99%), specificity was 81% (95% CI 77-84%), the associated positive predictive value (PPV) was 46% (95% CI 38-54%), and the NPV was 99% (95% CI 98-100%). Combined hrHPV and cytology testing yielded the best test characteristics.We propose to include hrHPV testing in conjunction with cytology for monitoring women treated for CIN 3. Some follow-up visits for women testing negative for both hrHPV and cytology can be skipped. In western countries, this could mean that for women double negative at 6 months, retesting at 12 months should be skipped while keeping the 24-month follow-up visit.

Publication Types:
• Meta-Analysis
• Review

Ann Acad Med Singapore. 2003 Sep;32(5):590-5; quiz 596.

Human papillomavirus triage of patients with atypical squamous cells of undetermined significance on cervical Papanicolaou smear.

Kirby TO, Huh WK, Partridge EE. Division of Gynecologic Oncology, University of Alabama at Birmingham, OHB Room 538, 619 19th Street South, Birmingham, AL 35249-7333, USA.

INTRODUCTION: The recent development of affordable human papillomavirus (HPV) testing has prompted consideration of its use as adjuvant and primary screening for cervical dysplasia. This review focuses on the use of HPV testing in triage management of atypical squamous cells of undetermined significance (ASC-US) Pap smears. MATERIALS AND METHODS: A Medline search was performed for articles relevant to HPV testing as a triage strategy for ASC-US Paps. Key references from other papers that were not included in the search were also reviewed. Findings from the major randomised trials were then summarised. RESULTS: Reflex HPV testing with hybrid capture is at least as effective and potentially cheaper than repeat cytology for evaluation of an ASC-US Pap. It also avoids 50% of colposcopies that would normally be performed if immediate colposcopy were done for all ASC-US Paps, while retaining excellent negative predictive value. CONCLUSION: Reflex HPV testing using liquid-based cytology is the preferred management strategy for triage of ASC-US Paps.

Publication Types:
• Review
• Review, Tutorial

Hpv Viruses - HPV and Cervical Dysplasia Links

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Gynecology Research - Cervical Dysplasia - Database of medical research articles on women's health involving stress effects, psychneuroimmunolgy, and mind-body techniques.