The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care

Kaul, Karen L.; Sabatini, Linda M.; Tsongalis, Gregory J.; Caliendo, Angela M.; Olsen, Randall J.; Ashwood, Edward R.; Bale, Sherri; Benirschke, Robert; Carlow, Dean; Funke, Birgit H.; Grody, Wayne W.; Hayden, Randall T.; Hegde, Madhuri; Lyon, Elaine; Murata, Kazunori; Pessin, Melissa; Press, Richard D.; Thomson, Richard B.

Human papilloma virus (HPV), the causative agent of genital warts, has been implicated in the development of *99% of cervical cancers. 23 More than 200 HPV genotypes have been described, 24 and approximately 40 are capable of infecting the human genital tract. 25 Of these, a relative few are known to cause cervical cancer and other malignancies; these can be identified by genotyping. Today, 4 assays are FDA approved for detecting high-risk HPV genotype strains in cervical specimens. [26] [27] [28] [29] These tests are routinely used to confirm the presence of an HPV infection, screen for cervical cancer, and refer cases with an indeterminate cytology examination. 30 During the past decade, a rise in oropharyngeal squamous cell cancer, primarily in 40 to 55-year-old Caucasian males with limited alcohol and tobacco exposure, has been described. 31 Unexpectedly, investigators discovered the frequent presence of high-risk HPV genotype strains in these lesions. Human papilloma virus-positive head and neck cancer is biologically distinct from HPV-negative disease. Patients with HPV-driven tumors have a significantly better prognosis, including response to chemoradiation therapy and overall survival, compared to HPV-negative patients. 32 Therefore, testing head and neck cancer specimens for high-risk HPV genotypes has become standard of care and is used to guide treatment. 33, 34 However, the HPV tests that are FDA approved for cervical specimens have not been approved for head and neck cancer, leaving a critical gap for patient care. Clinical laboratories have thus had to develop new assays or modified the existing FDA-approved ones to detect high-risk HPV genotypes in head and neck cancer specimens. Inclusion of patients in several clinical trials is based on these LDPs (www.clinicaltrials.gov. Accessed April 27, 2017). Without laboratory-developed tests, patients with head and neck cancer cannot benefit from personalized treatment strategies.