Cervical cancer is the fourth most common cancer in women globally. While its screening and prevention remains critical, in reality it is often overlooked.
To learn more about the impact of diagnostic advances on cervical cancer care, we connected with Snehal Bhoola, Associate Clinical Professor and Gynecologic Oncologist, City of Hope Phoenix.
From your perspective, where are we making the greatest progress in cervical cancer prevention and early detection – and where do diagnostic gaps still remain?
Experts now have a much clearer understanding of how cervical cancer develops and how it can be prevented through human papillomavirus (HPV) vaccination. Widespread access to HPV vaccines has made cervical cancer one of the most preventable cancers. Among adolescents aged 13-17 years in the US, approximately 78 percent have received at least one vaccine dose.
Despite these advances, health disparities continue to play a significant role. Cervical cancer can take 15-20 years to develop and often progresses without noticeable symptoms, making regular screening critical. Women who do not receive routine Papanicolaou (Pap) testing are at higher risk, particularly those with limited access to specialized care. Barriers related to race, gender, geographic location, education, and other social determinants of health continue to affect equitable access to prevention and screening. Gaps also remain in awareness efforts to address myths and misconceptions about vaccination and screening.
What should pathologists and laboratory professionals understand about current recommendations for primary HPV testing, co-testing, and cytology?
HPV testing is playing an increasingly central role in cervical cancer screening as guidelines shift toward approaches that more closely reflect the biology of cervical carcinogenesis. Persistent infection with high-risk HPV is a necessary precursor to nearly all cervical cancers, making HPV testing more sensitive than cytology for detecting high-grade precancer. This increased sensitivity supports longer screening intervals while maintaining, or improving, cancer prevention outcomes.
Advantages of primary HPV testing include a higher negative predictive value, earlier identification of individuals at true risk, reduced screening frequency, and the ability to incorporate self-collected specimens, which may improve access and equity.
However, primary HPV testing also presents challenges. Its lower specificity compared with cytology can result in more positive test results, increased patient anxiety, and potential over-referral for follow-up if triage strategies are not carefully implemented. The transition also places new demands on laboratories, including assay validation, management of increased HPV test volumes, and maintenance of cytology expertise for triage and diagnostic evaluation, even as overall Pap test volumes decline.
How has the transition toward HPV-based screening changed the way cervical precancers and cancers are detected in clinical practice?
The shift toward HPV-based screening has moved cervical cancer detection from primarily identifying abnormal cells to detecting the underlying cause of disease earlier in its course. Rather than waiting for precancerous cytologic changes to appear, clinicians can now identify high-risk HPV infections that signal elevated risk years before invasive cancer develops. This approach enables earlier risk stratification, longer screening intervals for individuals with negative HPV results, and more targeted follow-up for those who test positive. As a result, fewer cancers are missed between screenings, and many invasive cancers are now diagnosed after a prior HPV-positive result rather than as unexpected findings.
At the same time, HPV-based screening has redefined the role of cytology. Pap testing is increasingly used as a triage and diagnostic tool to help determine which HPV-positive patients require closer evaluation, such as colposcopy, rather than as a universal primary screening test. While this strategy improves overall sensitivity, it requires careful management to avoid overtesting and overtreatment, as many HPV infections resolve without intervention. Overall, HPV-based screening represents a more proactive, biology-driven approach to cervical cancer prevention, with clinical workflows increasingly focused on risk stratification rather than routine cytologic screening for all individuals.
HPV vaccination is a cornerstone of cervical cancer prevention. Are you already seeing its impact in pathology specimens or screening trends, and what changes do you anticipate as vaccinated cohorts age?
The Centers for Disease Control and Prevention (CDC) estimates that HPV vaccination prevents more than 90 percent of cervical cancers caused by HPV. Recent studies suggest that cervical cancer could be eliminated in the next century, largely through public health strategies that prioritize high HPV vaccination coverage in children and regular screening for women.
What breakdowns in the screening and diagnostic pathway most commonly contribute to delayed diagnosis?
Missed or inadequate screening, persistent health care disparities, and limited access to specialized care remain major barriers to early diagnosis and treatment. Expanding access to regular screening from a young age and improving education about cervical cancer are key steps toward reducing advanced disease in future generations. Most patients who present with advanced cervical cancer report that they have not received regular medical care, most often because of financial barriers or limited access to nearby health services.
What warning signs should prompt immediate diagnostic evaluation, even in patients who believe they are “up to date” on screening?
Abnormal vaginal bleeding, pelvic pain, or pain during sexual intercourse are symptoms that warrant prompt medical evaluation. These findings often occur at later stages of disease, and because cervical cancer can take 15-20 years to develop, regular screening remains the most important method for early detection.
What emerging diagnostic advances do you believe will further reduce the burden of cervical cancer?
Looking ahead, emerging diagnostic advances are expected to make cervical cancer screening more precise, efficient, and patient centered. One key development is extended HPV genotyping, which goes beyond identifying the presence of “high-risk HPV” to distinguish specific genotypes with differing cancer risk. Identifying infection with HPV16 or HPV18 – types responsible for most cervical cancers – allows clinicians to better tailor follow-up, prioritize colposcopy for those at highest risk, and safely monitor others with less intensive management. This risk-based approach has the potential to reduce unnecessary procedures while maintaining effective cancer prevention.
In parallel, molecular triage strategies, including HPV viral load assessment, DNA methylation markers, host gene expression profiles, and dual-stain biomarkers such as p16/Ki-67, offer tools to differentiate transient infections from those more likely to progress to precancer. When used after a positive HPV screen, these tests can improve specificity and help identify patients who truly require intervention. Together, extended genotyping and molecular triage reflect a shift toward personalized, biology-driven screening algorithms that may reduce overtreatment, improve patient experience, and further lower cervical cancer incidence, particularly when combined with expanded screening access and HPV vaccination.
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