Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older

Abstract

Given the strong etiologic link between high-risk HPV infection and cervical cancer high-risk HPV testing is now being considered as an alternative for cytology-based cervical cancer screening. Many test systems have been developed that can detect the broad spectrum of hrHPV types in one assay. However, for screening purposes the detection of high-risk HPV is not inherently useful unless it is informative for the presence of high-grade cervical intraepithelial neoplasia (CIN 2/3) or cancer. Candidate high-risk HPV tests to be used for screening should reach an optimal balance between clinical sensitivity and specificity for detection of high-grade CIN and cervical cancer to minimize redundant or excessive follow-up procedures for high-risk HPV positive women without cervical lesions. Data from various large screening studies have shown that high-risk HPV testing by hybrid capture 2 and GP5+/6+-PCR yields considerably better results in the detection of CIN 2/3 than cytology. The data from these studies can be used to guide the translation of high-risk HPV testing into clinical practice by setting standards of test performance and characteristics. On the basis of these data we have developed guidelines for highrisk HPV test requirements for primary cervical screening and validation guidelines for candidate HPV assays. ' 2008 Wiley-Liss, Inc.Key words: HPV-DNA testing; cervical screening; HPV test guidelines; HPV test requirements; HPV test statistics It is now well-established and widely, if not universally, accepted that virtually all cervical cancer and its immediate precancerous lesions arise from persisting cervical infections by $15 cancer-associated (high-risk or hr) human papillomavirus (hrHPV) genotypes.1,2 The most important of these HPV genotypes are HPV16 and HPV18, which account for $70% of all invasive cervical cancers with minor variations in this percentage between continents.3 A new paradigm of cervical carcinogenesis replaces an older model of stepwise progression from low-grade to highgrade morphological changes and can now be summarized as four reliably measured stages: (i) HPV acquisition, (ii) HPV persistence (vs. clearance), (iii) progression of a persisting infection to cervical precancer (with incidental co-occurrence of both conditions) and (iv) invasion. 4,5 On the basis of this nearly absolute etiologic link between carcinogenic HPV and cervical cancer, testing for hrHPV is now being considered as an alternative for cytology-based cervical cancer screening. However, before cost-effective implementation of population-based hrHPV testing in cervical cancer screening and prevention can be envisaged, any candidate HPV testing technologies must offer an optimal balance between clinical sensitivity and specificity for detection of cervical intraepithelial neoplasia grade 2 or 3 and treatable cancer (!CIN 2) to minimize redundant or excessive follow-up procedures. Reliable clinical performance needs to be established before any candidate screening test is widely disseminated and adopted into cl...

Global Proficiency Study of Human Papillomavirus Genotyping

“…It should be emphasized that the current proficiency panel study was designed to evaluate the performance of HPV testing and typing tests used in HPV vaccinology and HPV surveillance but not for evaluation of HPV tests used in cervical cancer screening (12). The demands on performance of HPVtyping assays vary depending on the purpose of the testing.…”

“…In vaccinology, high sensitivity is needed for clinical vaccine trials, as failure to detect prevalent infections at entry may result in apparent vaccine failures. In contrast, the clinical HPV-associated diseases, such as high-grade cervical intraepithelial neoplasia, typically contain larger amounts of virus, and cervicalscreening programs using HPV testing do not have as high demands on sensitivity (12). Guidelines for evaluations of such tests have recently been published (12).…”

The Value of Partial HPV Genotyping After Conization of Cervical Dysplasias

“…In recent decades the Hybrid Capture 2 HPV DNA Test (hc2; Qiagen, Hilden, Germany) was the most commonly used HPV test in clinical practice worldwide and in studies was most often the primary method for hr-HPV detection [13][14][15]. In addition, the hc2 is the standard against which new HPV test methods are measured; to be regarded as suitable tests non-inferiority to hc2 in terms of clinical sensitivity and specificity must be demonstrated [15,16].…”

“…In addition, the hc2 is the standard against which new HPV test methods are measured; to be regarded as suitable tests non-inferiority to hc2 in terms of clinical sensitivity and specificity must be demonstrated [15,16].…”

Importance of HPV Genotyping for the Screening, Therapy and Management of Cervical Neoplasias

“…Most commonly available, commercial PCR-based tests have therefore adapted their detection thresholds accordingly. The disadvantage of PCR-based assays is the limited clinical experience, although numerous studies of these tests have been done in recent years [1,2].…”