Accuracy of p53 codon 72 polymorphism status determined by multiple laboratory methods: a latent class model analysis

Area of Science:

• Genetics
• Molecular Biology
• Gynecologic Oncology

Background:

• Inconsistent findings link p53 codon 72 polymorphism (rs1042522) to cervical neoplasia.
• Multiple p53 genotyping methods exist, but accuracy and discrepancies are concerns.

Purpose of the Study:

• To evaluate the accuracy of six p53 genotyping methods using latent class models (LCM).
• To assess the association between p53 status and cervical abnormalities, accounting for test inaccuracy.

Main Methods:

• Latent class models (LCM) were employed to estimate the true accuracy of six p53 determination methods.
• The association between p53 status and cytological cervical abnormalities was examined.

Main Results:

• Pairwise disagreement among laboratory methods was around 10%.
• LCM analysis indicated that each method was most likely to correctly classify a woman's p53 status.
• Women with Arg/Arg genotype had the highest risk of squamous intraepithelial lesions (SIL).
• Test accuracy was independent of cytology, with no strong evidence of correlated test errors.

Conclusions:

• LCM provides unbiased test accuracy estimates, unlike empirical analyses that ignore laboratory errors.
• LCM resolves ambiguities from test discrepancies, eliminating the need for a single "gold" standard.
• The LCM approach is applicable to other scenarios with multiple non-gold standard tests.