A working group from the Lower Anogenital Squamous Terminology (LAST) Standardization Project, an interdisciplinary project led by the College of American Pathologists (CAP) and the American Society for Colposcopy and Cervical Pathology (ASCCP), has published consensus recommendations to standardize the histopathologic terminology for squamous epithelial lesions of the lower anogenital tract associated with human papillomavirus and to guide optimal biomarker use, according to Ventana Medical Systems, a member of the Roche Group.

These guidelines for pathologists include strong recommendations in support of the adjunctive use of the p16 biomarker in certain scenarios to support accurate diagnoses of pre-cancerous squamous lesions of the cervix and other lower genital tract sites.

The LAST biomarker work group concluded that the p16 biomarker, developed by mtm Laboratories of Germany and marketed as CINtecR p16 Histology, is the only biomarker "with sufficient evidence on which to make recommendation regarding use in lower anogenital tract squamous lesions."

mtm was acquired by Roche last year and Roche Diagnostics GmbH and Ventana are the exclusive provider of p16 for clinical use. The CINtecR p16 Histology product has recently been launched for use with Ventana BenchMark XT and BenchMark ULTRA IHC/ISH instruments using Ventana OptiView DAB IHC or ultraView DAB detection.

Pathologists are often challenged to distinguish between benign lesions caused by transient HPV infections that clear spontaneously from those persistent infections that drive oncogenic transformation that can lead to cancer. In addition, overtreatment in young women can lead to increased risks in pregnancy, including premature labor and ruptured membranes.

The LAST work groups were constituted to help address these and other challenges associated with the diagnosis of cervical and other HPV-associated anogenital lesions. As part of its recommendations contributing to a standardized terminology, the biomarker work group recommended that the p16 biomarker be used in conjunction with H&E morphology to aid in differential diagnosis between CIN2/CIN3 and mimics of pre-cancer adjudicate when there is professional disagreement about a diagnosis, as well as in several other situations, such as cases in which the results of a Pap smear indicate high grade pre-cancerous changes and the biopsy appears to be normal or low-grade precancerous disease.

"We try to save the patient a second colposcopy and get the right diagnosis, and one way is if a normal biopsy is associated with an HSIL Pap test, consider doing a p16 stain,” said Mark H. Stoler, co-chair of LAST biomarker work group, in CAP Today. “A significant percentage of the time, this will highlight an area of missed CIN2/3 [high-grade precancerous cells] and will save the patient a second biopsy."

The LAST biomarker work group had reviewed more than 2,000 scientific publications evaluating the use of molecular markers in conjunction with H&E morphology in lower anogenital tract tissues.

"The publication of these recommendations supporting the use of p16 as the only biomarker with sufficient evidence for its use in lower anogenital tract histopathology interpretation underscores our conviction that technical and clinical validation is the key to establishing new medical parameters, such as biomarker-based diagnostic adjuncts," explained Ruediger Ridder, CSO of mtm laboratories.

In the U.S., the CINtec p16 Histology product is available as a Class I exempt IVD without claims. The utility, as described in this press release and as recommended by the cited CAP/ASCCP recommendations, has not been cleared or approved by the FDA.