Bridging the gap between infection and detection: Biological, clinical, and health system contributors to diagnostic delay in HPV-associated cervical cancer.

Cervical cancer is the most common gynecological cancer among women worldwide. Nearly all cases of cervical cancer are attributable to persistent human papillomavirus (HPV), a vaccine-preventable sexually transmitted infection. Although HPV is usually harmless, long-lasting infections are responsible for nearly 13,500 projected new cases of cervical cancer in 2026 in the United States, according to the American Cancer Society's annual Cancer Statistics report. Despite strong public programs and efforts to improve HPV vaccination rates, the US has lower vaccine coverage than other high-income countries. Beyond suboptimal prevention, delays in cervical cancer detection, access to equitable healthcare, and diagnostic confirmation contribute to the later-stage diagnosis in HPV-related cervical cancers (HPV-CC). This review highlights the diagnostic and prognostic roles of key biomarkers, including p16, p16/Ki-67 dual staining, epigenetic markers such as CADM1 and MAL, and the PD-L1 immune checkpoint marker, in improving risk stratification and diagnostic accuracy in HPV-associated cervical cancer. Furthermore, systemic factors such as insurance status, racial and socioeconomic disparities, access to care, and structural barriers to screening will also be explored. Collectively, this review emphasizes the need for the integration of molecular diagnostics with equitable screening and healthcare delivery to reduce diagnostic delays in cervical cancer within the United States to ultimately improve risk-specific treatment and clinical outcomes.