Relevance of the Pap Test: A Report of HPV-DNA Test-Negative High-Grade Squamous Intraepithelial Lesions of the Female Lower Genital Tract

Abstract

Objective: A vast majority of cervicovaginal intraepithelial lesions are caused by high-risk human papillomaviruses (HPVs). The Pap test has been the sole method used for the screening of cervicovaginal squamous intraepithelial lesions (SIL). Recently, the FDA approved an HPV-DNA assay as a method of primary screening. We report on a series of FDA-approved HPV-DNA test-negative SIL with HPV genotyping, using an alternative method on the corresponding surgical biopsy specimens. Study Design: A retrospective review identified cytology-positive HPV-negative cases over a 15-month period at a tertiary care gynecologic oncology institution. Corresponding biopsies were reviewed and genotyped for high-risk HPVs. Results: Of the 18,200 total cases, 17 patients meeting the study criteria were selected with 27 surgical specimens corresponding to their cytologic diagnoses. Four patients with high-grade lesions were identified, 3 of whom (75%) were positive for HPV. One of these 4 patients (25%) showed high-grade SIL on biopsies from 4 separate sites in the cervix and vagina. Multiviral HPV infections were frequent. Conclusions: We discuss the relevance of cotesting for screening cervical SILs and emphasize that false-negative results are possible with the FDA-approved HPV screening assay, also in patients with high-grade SIL. These cases may be detectable by cytologic examination and this suggests that the Pap test remains an important diagnostic tool.

Addressing Confusion about the Risks and Benefits of Co-Testing versus Human Papillomavirus Testing for Cervical Cancer Screening

“…In conclusion, the data presented by Hui et al [1] support our contention that, while co-testing is likely to detect a tiny portion of high-grade lesions (at a significant financial and resource cost), it is also highly likely to cause women to undergo unnecessary surgical procedures.…”

“…We were confused by the paper presented by Hui et al [1] as it appears to present the somewhat narrow view of a co-testing (human papillomavirus [HPV] nucleic acid testing [NAT] combined with cervical cytology) paradigm for cervical screening as being superior to an HPV-based program.…”

Assessment of 100% Rapid Review as an Effective Tool for Internal Quality Control in Cytopathological Services

“…Testing strategies involving the detection of HPV have been developed to improve the efficacy of cytologic evaluation alone. Molecular detection methods (HPV DNA assays) have been used to step up the primary screening programs [32] .…”

“…The 100%-RR could be a useful tool for minimizing the risk of the false-negative characteristics of the HPV screening test. Hui et al [32] presented HPV DNA test-negative, Pap-positive cervicovaginal squamous intraepithelial lesions with HPV genotyping data from corresponding surgical tissue biopsies. A follow-up Pap smear may be essential in particular patients with negative HPV DNA screening results because an important aspect of primary screening is to minimize false negatives.…”

“…While no screening test can infallibly detect all cases, the findings of our study support the use of both screening tools available to ensure that patients receive optimum care. The Pap test, therefore, remains a necessary procedure in screening for cervical cancer [32] .…”