The Empirical Paradox of Primary HPV Screening: Increased Invasive Cancer Incidence in the U.S. Compared to Annual Cytology at a Peruvian National Hospital

Abstract Background. The global transition toward primary human papillomavirus (HPV) testing as a screening strategy has largely replaced conventional cytology, based on the assumption that targeting the causal agent will more effectively prevent invasive cervical cancer. However, this hypothesis must be evaluated not only by analytical sensitivity but by its real-world impact on reducing advanced disease. In science, an empirical paradox —a result that directly contradicts the theoretical prediction— epistemologically invalidates the underlying argument. If primary HPV screening increases the incidence of invasive cancer, then it fails its fundamental objective. Methods. A retrospective, descriptive, and analytical study was conducted using publicly available data from the Surveillance, Epidemiology, and End Results (SEER), Centers for Disease Control and Prevention (CDC), and American Cancer Society (ACS) for the United States across two periods: Group A (2010–2014; cytology-based) and Group B (2020–2024; primary HPV-based). These were compared with primary data from the Hospital Alberto Sabogal Sologuren (HVAS), ESSALUD, Callao, Peru (2019–2024; n = 86,800 women), where annual conventional cytology remains the standard. Analyzed categories included: low-grade squamous intraepithelial lesion (LSIL/LIEBG), high-grade squamous intraepithelial lesion (HSIL/LIEAG), atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells—cannot exclude high-grade lesion (ASC-H), atypical glandular cells (AGC), invasive squamous cell carcinoma, and adenocarcinoma. Statistical comparisons were performed using the chi-square test (p < 0.05). Results. HVAS detected significantly higher rates of LSIL (0.607% vs. 0.448% and 0.333%) and HSIL (0.297% vs. 0.225% and 0.165%) than both U.S. groups (p < 0.001). Despite HPV testing’s superior sensitivity, the U.S. observed a 13.7% increase in invasive cervical cancer incidence between Group A and Group B (p = 0.014). In stark contrast, HVAS reported an invasive cancer rate of only 0.0081%. HVAS also identified 1,188 ASC-US (1.37%) and 151 ASC-H (0.17%) cases. Conclusions. Statistically significant differences favor cytology-based screening (Group A and HVAS) in reducing invasive cervical cancer incidence. The paradoxical rise in invasive cancers in the U.S. following implementation of primary HPV screening constitutes an empirical paradox that epistemologically refutes the claim that HPV-based screening reduces advanced disease. This paradox suggests that the loss of critical morphological information —including coilocytosis, ASC-US, ASC-H, and AGC — may compromise early detection. Conventional cytology, when performed with quality and appropriate frequency, remains irreplaceable. We recommend an integrated model: cytology as first-line screening, with HPV triage for equivocal results (ASC-US, ASC-H), thereby maximizing early lesion detection and minimizing invasive cancer.