GENETIC TESTING

Guidelines at a Glance

Screening for HIV

Published June 11 in the Journal of the American Medical Association.

The U.S. Preventive Services Task Force (USPSTF) recommends screening for HIV infection in adolescents and adults aged 15 to 65 years. Younger adolescents and older adults who are at increased risk of infection should also be screened. The USPSTF also recommends screening for HIV infection in all pregnant persons, including those who present in labor or at delivery whose HIV status is unknown.

The USPSTF found insufficient evidence to determine appropriate or optimal time intervals or strategies for repeat HIV screening, although acknowledged that repeat screening is “reasonable” for individuals at increased risk of HIV infection.

The task force recommends that when using a rapid HIV test for screening (e.g., women in labor), positive results should be confirmed.

This update confirms the guidance in the 2013 USPSTF recommendations.

Early-Pregnancy Screening for Preeclampsia

All pregnant women should be screened for preterm preeclampsia during the first-trimester with risk calculator assessing maternal risk factors and biomarkers, according to the International Federation of Gynecology and Obstetrics’ guidelines published May 20 in the International Journal of Obstetrics & Gynecology.

The test includes maternal risk factors, measurements of mean arterial pressure, serum placental growth factor, and uterine artery pulsatility index. If maternal serum pregnancy-associated plasma protein A is measured for routine first-trimester screening for fetal aneuploidies, the test result can be included for preeclampsia risk assessment. This screening can be adapted for screening in twin pregnancies.

FIGO considers early screening to be a measure that would most likely increase savings to the health system, but calls for more cost-effective analyses to be conducted to demonstrate the financial benefit of the screening strategy. These recommendations support earlier guidance published by the Fetal Medicine Foundation.

Recommendations for Clinical CYP2C9 Genotyping Allele Selection

A joint recommendation of the Association for Molecular Pathology and College of American Pathologists (CAP), published May 7 in the Journal of Molecular Diagnostics, defines a list of alleles that should be included in clinical CYP2C9 pharmacogenomic (PGx) tests.

Tier 1 recommended alleles (CYP2C9 *2, *3, *5, *6, *8, and *11.) are those that 1) have been well characterized and found to significantly affect the function of the protein and/or gene leading to a change in a drug response phenotype, 2) have a minor allele frequency in a population/ethnicity group, and 3) have publicly available reference materials. Alleles and variants that currently meet at least one, but not all three of the tier 1 criteria are included as tier 2 variant alleles (CYP2C9 *12, *13, and *15). The recommendation says that the variants can be applied to all CYP2C9-related medications.

The workgroups identified seven commercially available platforms for CYP2C9 genotyping. All platforms include Tier 1 alleles *2 and *3, however, only two include all recommended tier 1 alleles and the tier 2 alleles. The authors note, though, that most laboratories participating in CAP and the North American Specialized Coagulation Laboratory Association’s proficiency testing programs currently test for tier 1 alleles and the U.S. Food and Drug Administration recently approved 23andMe’s direct-to-consumer PGx test that includes most of the CYP2C9 tier 1 alleles.

“Our goal is to promote standardization of testing PGx genes and alleles across clinical laboratories,” writes Victoria M. Pratt, from CAP’s PGx work group.

Screening for Elevated Blood Lead Levels in Childhood and Pregnancy

The U.S. Preventive Services Task Force (USPSTF) updated its 2006 recommendation on screening for elevated blood lead levels in asymptomatic children aged 1 to 5 years and pregnant persons, but concluded that the current evidence is “insufficient” to assess the balance of benefits and harms related to screening for elevated blood lead levels.

The U.S. Centers for Disease Control and Prevention defines an elevated blood lead level as above 5 μg/dL. The USPSTF reports that capillary blood testing accurately identifies children with elevated blood lead levels, but could not make a determination regarding screening. The evidence was published April 16 in the Journal of the American Medical Association.

Other professional groups differ in their recommendations. The American Academy of Family Physicians recommends against routine screening in children of average risk, whereas the American Academy of Pediatrics recommends screening based on federal, state, and local requirements; in children living in high-prevalence areas (communities with ≥25 percent of housing built before 1960 or a prevalence of blood lead levels ≥5 μg/dL of ≥5 percent); in children with identified lead hazards or living in a home built before 1960 that is in poor repair or renovated in the past 6 months; or in children who are immigrants, refugees, or internationally adopted.

“Clinicians should understand the evidence but individualize decision making to the specific patient or situation,” writes Susan J. Curry, Ph.D., from the USPSTF.

Updated Guideline for Melanoma Management Calls for BRAF Testing

The National Comprehensive Cancer Network (NCCN) has issued an updated guideline for the management of cutaneous melanoma that recommends testing for BRAF mutations in patients with stage III melanoma who are at high risk for recurrence for whom future BRAF-directed therapy may be an option.

For patients with stage IV disease at either initial presentation or clinical recurrence being considered for targeted therapy, the updated guideline recommends obtaining tissue to ascertain alterations in BRAF, and possibly KIT, from preferably a biopsy of the metastasis or archival material.

More comprehensive genomic profiling (e.g., next-generation sequencing panels) canbe considered if the test results might guide future treatment decisions or eligibility for participation in a clinical trial, particularly if BRAF single-gene testing was negative.

NCCN recommendations for BRAF testing are similar to those from the European Association of Dermato Oncology and the European Society for Medical Oncology.

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