HPV Vaccination and Evolving Screening Strategies Continue to Shape Cervical Cancer Prevention Efforts

Cervical cancer is one of the most preventable malignancies in oncology, yet it remains the 4th most common form of cancer among women and continues to account for hundreds of thousands of deaths worldwide.¹ Persistent infection with oncogenic human papillomavirus (HPV) is one of the leading causes of cervical cancer, creating a uniquely actionable pathway for prevention through vaccination and early detection.² Over several decades, HPV vaccination programs and population-based screening efforts have led to substantial reductions in cervical cancer incidence, and scientific evidence supporting these strategies is robust^.2,3 However, significant logistical, socioeconomic, and educational barriers to access have hindered widespread vaccination, thereby limiting these gains.²

During Cervical Cancer Awareness Month, observed annually in January, OncLive®spoke with the following experts on the current state of HPV vaccination and screening in cervical cancer:

• Maurie Markman, MD, president of Medicine and Science at City of Hope Cancer Centers in Atlanta, Chicago and Phoenix, a professor in the Department of Medicine at City of Hope, and the editor-in-chief of OncologyLive
• Dana M. Chase, MD, a professor of Clinical Obstetrics and Gynecology in the Division of Gynecologic Oncology at UCLA Health
• Robert Neff, MD, a physician and associate professor of Gynecologic Oncology at the Ohio State Comprehensive Cancer Center—James

Together, these experts agreed that comprehensive provider education and cross-discipline communication remain vital for improving HPV screening and vaccination implementation in clinical practice. Furthermore, innovations such as single-dose HPV vaccination, advanced genotyping, and self-collected HPV tests may help address some of these challenges, but only if they are integrated thoughtfully into clinical workflows.

What is the global burden of HPV-related cervical cancer?

In the United States, approximately 13,490 new cases of invasive cervical cancer are diagnosed annually, with an estimated 4200 deaths each year.³ These figures persist despite the availability of effective screening programs and curative therapies, highlighting gaps in prevention and early detection. Of note, cervical precancers are diagnosed more frequently than invasive cervical cancer.

“Worldwide, it is estimated there will be more than 600,000 cases of invasive cervical cancer diagnosed, leading to 350,000 deaths,” Markman said, emphasizing the magnitude of this burden and its implications for clinical practice. “That number alone underscores why HPV-associated cancers represent a substantial public health concern.”

Although early-stage cervical cancer can often be cured via surgery or chemoradiation, treatment is associated with significant morbidity and cost burden, Markman stated, adding that outcomes in advanced or recurrent disease remain poor despite incremental improvements with systemic therapy and immunotherapy.

From a population perspective, prevention remains the most effective strategy to reduce both mortality and treatment-related morbidity in cervical cancer, experts emphasized. The 5-year relative survival rate of cervical cancer is 67.4%; however, when diagnosed at an early stage, this spike to 91%.² Early vaccination against HPV has proven successful in preventing this malignancy, with early vaccination resulting in a 40% reduction in cervical precancers and more than an 80% reduction in the overall risk of developing the disease.

“Many [studies] over the last decade [have shown] the benefits of HPV vaccination as fundamental [cervical] cancer prevention,” Markman summarized. “Few interventions in oncology offer this level of impact with such a strong safety record.”

What evidence supports HPV vaccination as cervical cancer prevention?

The efficacy and safety of HPV vaccination are supported by extensive randomized and population-based data. Early clinical trials demonstrated significant reductions in high-grade cervical intraepithelial neoplasia; more recent long-term follow-up studies have confirmed that these reductions translate into lower rates of invasive cervical cancer, and several meta-analyses of randomized-controlled trials (RCTs) have confirmed a reduction in the incidence of cervical intraepithelial neoplasia (CIN) with the vaccine without a substantive difference in serious adverse effects (AEs) vs control regimens.^4,5

Findings from a meta-analysis of 225 observational studies comprising over 132 million patients showed that women no older than 16 years of age who received the HPV vaccine were 80% less likely to develop cervical cancer than those who were unvaccinated (relative risk [RR], 0.20, 95% CI, 0.09-0.44; I² = 69%).⁴ Another large meta-analysis of 60 RCTs involving 157,414 participants demonstrated that patients 15 to 25 years of age who received the HPV vaccine experienced a 30% reduction in the incidence of grade 2 or higher CIN (RR, 0.70; 95% CI, 0.56- 0.88); this reduction in risk increased to 60% at 6 years (RR, 0.40, 95% CI 0.30-0.54).⁵

“The early studies focused on [CIN], a known precursor of cancer, but increasingly we are seeing data that demonstrate a reduction in the incidence of invasive cancers,” Markman said. “It takes time to see [that effect], but we’re getting more and more population-based studies showing [the consistency of benefit with HPV vaccination] across a variety of countries.”

The benefits of HPV vaccination extend beyond those vaccinated. Data from a 2026 study based on the Swedish National Screening Registry showed a decline in the incidence of high-grade cervical lesions among unvaccinated women who were eligible for HPV vaccination through a school-based program, indicating that herd protection can be achieved through high-coverage HPV vaccination.⁶

Equally important is the extensive safety record of HPV vaccination. Across clinical trials and real-world surveillance studies, no evidence has emerged linking HPV vaccination to serious long-term toxicities, he reasserted. “The toxicity question continues to come up,” Markman noted, “but the answer is that there is simply no evidence for serious toxicities of any kind that relate to HPV vaccination compared with control populations in the real world.”

What are the most persistent barriers to HPV vaccination and screening?

Despite strong evidence, HPV vaccination uptake in the United States remains below national targets.⁷ Although the Healthy People 2030 goal for HPV vaccination series completion is 80%, the rate of HPV vaccination for adolescents 13 to 15 years of age is 58.5%, and a 2025 study showed that current rates of up-to-date HPV vaccination in 1,848,813 ranged from 12.5% to 41.4% for patients across all racial and ethnic groups.

Additionally, unlike other childhood vaccines, HPV vaccination is not universally mandated for school entry, contributing to variability in uptake across regions and socioeconomic groups, Chase emphasized.

“[Some of the primary] issues that contribute to women not getting their pap smears and/or HPV testing is access to care and cost,” she said. “Going to a gynecologist is not as easy as going to urgent care or a primary care physician. Not all primary care physicians perform pelvic exams…and if patients don’t have access to insurance, a pap smear can be expensive.”

Stigma and prior trauma also deter some individuals from seeking gynecologic care and receiving pelvic examinations, leading to missed opportunities for screening, Chase noted. In addition, the target age range for prevention and screening often coincide with life stages characterized by competing priorities, such as education, employment, and family responsibilities, she said.

From a provider perspective, Chase shared that evolving guidelines have introduced additional complexity. Some clinicians trained during the era when cytology alone was the standard screening modality may be less familiar with primary HPV testing and genotyping, she explained. Ordering errors, incomplete testing, and inconsistent follow-up can result when practices have not fully adapted to updated recommendations.

Neff noted that system-level challenges also contribute to this disparity in implementation. “For [most of] the history of cervical cancer screening, [pap smears] required in-person visits. That requires providers to be available to patients in certain locations,” he said. “Getting patients in the door remains one of the biggest obstacles, but its [also a matter of] getting patients to physicians or providers who feel comfortable doing the exams.”

How are regulatory updates for HPV testing reshaping cervical cancer screening paradigms?

On January 5, 2026, the Health Resources and Services Administration released updated cervical cancer screening guidelines designating high-risk HPV (hrPHV) testing as the preferred screening method for women at average risk between 30 and 65 years of age.⁸ Critically, the guidelines also permit women in this age group to self-collect samples for hrHPV testing, in supervised clinical settings. Starting January 1, 2027, most private insurers will be required to cover self-collected HPV screening with no cost sharing.

“Additional studies that have looked at the option of self-collected HPV testing have shown [that it is] equally effective at identifying HPV variants as physician-collected [samples],” Neff said, highlighting the potential impact of this approach. “It offers an option for patients who are uncomfortable with exams or have difficulty accessing care, helping ensure they are not missed within screening windows. There's a lot of excitement around that option for the future.”

However, limitations remain, experts underscored. Current regulatory indications require sample collection within a clinical environment, and recommended screening intervals are shorter than those for clinician-collected tests due to the absence of a concurrent visual examination. As Neff cautioned, “One of the biggest logistical barriers is not having a visual exam…[this] introduces some concern. Because of that, negative self-collected tests are recommended at 3-year intervals rather than 5.”

HPV genotyping further refines risk assessment by distinguishing high-risk subtypes such as HPV16 and HPV18 from lower-risk strains, both Chase and Neff asserted. This stratification supports more individualized management, enabling intensified surveillance for those at highest risk while reducing unnecessary interventions for others. Concurrently, the increasing complexity of results underscores the need for provider education to prevent under- or overtreatment, Neff noted.

“We're all excited about having more data to manage patients more effectively and safely, potentially [reducing] harm,” he added. “On the other hand, screening tests can become overly burdensome for providers who are not regularly up-to-date with these new guidelines. The worry is that some of that new data on HPV genotyping may lead to either under- or over-treatment if these data are not disseminated and if that testing becomes available.”

What are some of the unresolved questions regarding HPV vaccination?

Another area of active debate regarding cervical cancer prevention is whether a single dose of HPV vaccine provides durable protection comparable to multi-dose regimens. On January 5, 2026, the Centers for Disease Control and Prevention revised the United States childhood and adolescent immunization schedule to recommend a single dose of HPV vaccination for all children, replacing the prior 2- or 3-dose series.⁹ The update, which was not recommended by the Advisory Committee on Immunization Practices, followed an internal federal review of immunization practices utilized in developed countries. The Department of Health and Human Services cited international alignment and emerging evidence supporting comparable efficacy with 1 dose.

One such study is a large-scale RTC from Costa Rica found that one dose of either a bivalent or nonvalent HPV vaccine provided comparable short-term protection against HPV16 or HPV18 to that seen with a standard 2-dose regimen, suggesting that this simplified vaccine strategy could increase vaccination rates in lower-resource settings.¹⁰

“The data are provocative… but we do not yet know the long-term effects of a single dose compared with 2 doses,” Markman stated, urging caution in interpreting these findings. “Are we going to be in a situation where after only a single dose… the cancer prevention strategy may be less effective [later]? Do we know what happens 5 or 10 years later? The answer is no, and that matters when we are talking about cancer prevention.”

Of note, the United States does not currently have a licensed single-dose HPV vaccine.⁹

Vaccination after treatment for HPV-related precancerous lesions is also being considered, as preliminary data suggest that vaccination following surgical excision may reduce the risk of subsequent abnormalities, even when the initial lesion is associated with vaccine-covered HPV types.¹¹ Findings from a meta-analysis of 11 studies featuring 21,310 patients showed that the HPV vaccine reduced the risk of relapse as an adjunct to CIN, although comparing the rates of CIN recurrence in patients who received the vaccine prior to vs after surgery was not possible due to a lack of standardization in the timing of HPV vaccination.

“Is there a benefit at this point [after surgery] to vaccinate? The data suggest that the answer to this may be yes,” Markman added. “Even if the abnormality found was related to a component in the vaccination, it is possible that now vaccinating them will decrease the risk of developing a subsequent abnormality.”

Neff noted that therapeutic HPV vaccines represent an additional frontier, aiming to treat established disease rather than prevent infection. Although investigational, he stated that these approaches reflect a broader shift toward immunologic strategies in HPV-associated cancers.

How can oncologists continue to advocate for the adoption of best practices for HPV screening and vaccination?

All 3 experts agreed that gynecologic oncologists and other specialists play a key role in supporting primary care providers through guidance on screening algorithms, interpretation of HPV results, and appropriate referral pathways.

Neff emphasized the importance of collaboration. “We need open lines of communication with community partners so they feel comfortable discussing abnormal results and new testing options,” he said. “That connection ensures that patients get timely, appropriate care.”

Chase underscored the need for persistent vaccine advocacy in cervical cancer. “HPV vaccination uptake in the United States is still below where we want it to be,” she said. “Targeting individuals in their 20s and 30s who missed vaccination and screening is critical, because those are the patients who later present with advanced disease.”

Looking ahead, experts anticipate a continued overall decline in cervical cancer incidence driven by vaccination and improved screening technologies. At the same time, there is concern that disease presentation may increasingly shift toward more advanced-stage diagnoses among unvaccinated and underscreened populations.

“We’ll need to really focus on the treatment of more locally advanced disease, which is going to be more difficult to treat and also have a worse overall prognosis,” Neff predicted. “[With this], those of us the world of treating cervical cancer need to be more thoughtful in terms of guiding new evidence-based treatments toward…patient populations with the highest burden and making sure that newer therapies are available to that patient population, which may not be in suburban academic medical practices.”

References

1. Cervical cancer. World Health Organization. December 2, 2025. Accessed January 30, 2026. https://www.who.int/news-room/fact-sheets/detail/cervical-cancer
2. Nabi S, Mimba BR, Akunne O, et al. Eliminating cervical cancer: the impact of screening and human papilloma virus vaccination. Prev Chronic Dis. 2025;22:E46. doi:10.5888/pcd22.250127
3. Key statistics for cervical cancer. American Cancer Society. Updated January 14, 2026. Accessed January 30, 2026. https://www.cancer.org/cancer/types/cervical-cancer/about/key-statistics.html
4. Henschke N, Bergman H, Buckley BS, et al. Effects of human papillomavirus (HPV) vaccination programmes on community rates of HPV-related disease and harms from vaccination. Cochrane Database Syst Rev. 2025;11(11):CD015363. doi:10.1002/14651858.CD015363.pub2
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6. Meglic E, Ploner A, Clements M, Elfström M, et al. Herd effect of human papillomavirus vaccination on incidence of high-grade cervical lesions: a population-based cohort study in Sweden. Lancet Public Health. 2026;11(1):e35-e43. doi:10.1016/S2468-2667(25)00297-X
7. Ulmer K, Lyon-Scott K, Wasson N, Haderlein TP, Bruegl A. HPV vaccination in community health organizations: what is going right and how can it be replicated?. Cancer Causes Control. 2025;36(11):1525-1537. doi:10.1007/s10552-025-02040-0
8. HRSA announces updated cervical cancer screening guidelines. News Release. Society for Gynecologic Oncology. January 14, 2026. Accessed January 30, 2026. https://www.sgo.org/news/hrsa-announces-updated-cervical-cancer-screening-guidelines/
9. The new U.S. childhood vaccine schedule. News Release. Society for Gynecologic Oncology. January 14, 2026. Accessed January 30, 2026.https://www.sgo.org/news/the-new-u-s-childhood-vaccine-schedule-a-key-change-for-hpv-immunization/#:~:text=of%20Gynecologic%20Oncology-,The%20New%20U.S.%20Childhood%20Vaccine%20Schedule:%20A%20Key%20Change%20for,children%20from%2013%20to%207.
10. Kreimer AR, Porras C, Liu D, et al. Noninferiority of one HPV vaccine dose to two doses. N Engl J Med. 2025;393(24):2421-2433. doi:10.1056/NEJMoa2506765
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