Cervical cancer is the fourth most common cancer among women worldwide, with higher prevalence in low-resource countries due to limited access to screening and HPV vaccination. Nucleic acid amplification tests (NAATs) such as Xpert HPV (Cepheid), enable rapid detection of high-risk HPV (HR-HPV) genotypes. However, the clinical significance of weak and late amplification signals (cycle threshold ≥ 38), interpreted as negative, remains unclear. In this study, a comparison with cytological results aimed to assess their significance. Out of 6846 cervical samples analyzed at Brest University Hospital (Jan. 2022-June 2024), 45 showed late amplification and were reported negative by Xpert. These samples were retested using an in-house HPV pangenotypic PCR followed by genotyping (LiPA) and were assessed by cytology. Of the 44 available cytology results, 65.9% were normal, 15.9% showed low-grade squamous intraepithelial lesions (LSIL), and 18.2% were atypical squamous cells of undetermined significance (ASC-US). No high-grade squamous intraepithelial lesions (HSIL) were found at initial cytology. Among the 42 samples available for in-house PCR, 59.5% tested positive for HPV, and 11.9% were confirmed as HR-HPV genotypes (types 52, 56, 35). Additionally, among patients with available HPV history, 73.3% had a previous positive test. In 91% of these cases, the genotype suspected during the late amplification was concordant with the previous infection. During the 1-year follow-up, one patient initially classified as LSIL developed a histologically confirmed HSIL (CIN2) and needed treatment by conization, whereas 3 others were found to have low-grade CIN1 cell lesions. Overall, for 15 out of 45 patients with weak HPV PCR signal and abnormal cytology (33.3%), clinicians chose to recommend a closer 1-year follow-up and not at 5 years as recommended for HPV negative patients. In conclusion, cytological triage and a review of patient history remain crucial to avoid missing at-risk patients, especially in settings where HPV-negative women are re-screened only 5 years later. A multicenter study using Xpert HPV and other automated platforms is recommended to strengthen these findings and further explore potential correlations between viral load and clinical severity.
Lemoine et al. (Wed,) studied this question.