Diagnostic sensitivity for invasive cervical carcinoma of high risk HPV tests performed on SurePath™ liquid-based pap specimens.

We thank Dr Nance for providing additional data on his experience with Hybrid Capture 2 (HC2) (Qiagen NV, Hilden, Germany) Laboratory Developed Testing (LDT) from the SurePath™ (Becton-Dickinson, Franklin Lakes, NJ, USA) vial. As mentioned previously, we believe this is the kind of retrospective data that the laboratory profession should be monitoring nationwide,1,2 especially given proposed extended five year screening intervals for many women with negative high risk (hr) HPV test results.3 The SurePath™ HC2 hrHPV LDT data cited by Dr Nance differs significantly from published data reported by several US academic centers. A study from Emory University of patients with ASC-H (atypical squamous cells - cannot exclude high grade squamous intraepithelial lesion) Sure-Path™ cytologic findings, for example, reported positive hrHPV HC2 LDT results from the SurePath™ vial in only 11 of 21 patients (52%) with follow-up CIN3 biopsy findings of 48 of 61 patients (79%) with follow-up CIN2 biopsy findings.4 More recently, Johns Hopkins University, reported positive hrHPV HC2 LDT results from the SurePath™ vial in 48 of 57 patients (84%) with HSIL SurePath™ cytology results, zero of six patients with SurePath™ cytologic findings of adenocarcinoma, and one of two patients with SurePath™ cytologic findings of squamous cell carcinoma.5 Since current achievable standards have been proposed that an HPV test should have clinical sensitivity to detect at least 89%–95% of existing CIN3+ lesions,6 these published findings and a number other cautionary observations we made in our initial report7 should be of concern regarding this widespread LDT. Furthermore, since SurePath™ HPV testing is not standardized according to any US Food and Drug Administration (FDA)-validated protocol, it is not possible to reliably extrapolate findings from any one laboratory to others. In fact, we are not aware of any published SurePath™ hrHPV LDT validation study which has published its methodology in sufficient detail so that it might be independently implemented and verified by other laboratories. Under current regulations, SurePath™ hrHPV LDT methods cannot be promoted by the manufacturers. LDT methods used in practices appear to vary quite widely, based on conversations with individual laboratories. Therefore, we applaud Dr Nance’s recent announcement to introduce in his laboratory co-collection of HPV test specimens in a separate FDA-approved collection vial. This, of course, is the approach the SurePath™ manufacturer itself recommended in its June 8, 2012 Technical Bulletin (BD Diagnostics, personal communication, June, 2012). Dr Nance’s report of positive hrHPV SurePath™ vial LDT results in seven of seven patients with HPV testing within 5 years of a diagnosis of cervical squamous cell carcinoma is itself somewhat surprising. Available international data indicate that negative hrHPV test results increase significantly as testing is less proximate to the time of diagnosis, probably due to increased difficulty in sampling infected lesional cells (sampling false negatives).8 In the largest available US study, baseline HC2 hrHPV test results collected in FDA-approved Specimen Transport Medium (STM) vials within 5 years of cervical cancer diagnoses were positive at baseline in only 60 of 87 cervical cancer patients (69%).9 It would be useful to know the full details of the LDT method(s) used by Dr Nance’s laboratory during the time periods mentioned, who originally developed this methodology, when the methodology was developed, and to have more information on the proximity of the seven HPV tests to the final diagnoses of squamous carcinoma. Ideally, in our opinion, what is needed is an FDA-approved SurePath™ hrHPV methodology based on supporting clinical trial data, so that user laboratories nationwide that wish to perform HPV testing from the SurePath™ vial can implement a standardized FDA-validated HPV testing method. Both the American Cancer Society and the American College of Obstetricians and Gynecologists now recommend that only FDA-approved HPV test methods be relied on in cervical screening.3 Laboratories choosing not to follow professional organization and manufacturer recommendations should make their validation data available upon request for independent review along with detailed information on the precise HPV testing method(s) they have used. Only then can findings be scientifically tested and independently scrutinized for validity and reproducibility. Patients deserve to be tested using scientifically sound methods. Clinicians should be able to trust that HPV testing used for patient care has been determined to meet current standards established through rigorous FDA trials and independent review. Until laboratories using LDT for HPV testing are willing to share their detailed methods and data so that their testing results are open to scientific scrutiny, reliance on FDA-approved testing methods is prudent.