Updates on Cervical Cancer Prevention: Summary and Projected Effect
September 1, 2025
By Rebecca B. Perkins, MD, MSc
Each year in the United States, nearly 100,000 people are treated for cervical precancer, more than 14,000 people are diagnosed with cervical cancer, and more than 4,000 people die from cervical cancer.1 With human papillomavirus (HPV) vaccination and screening, we have the tools to nearly eliminate cervical cancer, and cancer rates have dramatically decreased in women younger than 30 years of age because of vaccination. However, most adult women in the United States today were born too late to benefit from vaccination in early adolescence.
Current data show that cervical cancer incidence and mortality are rising among women aged 30-44 years.2 This special feature will review the effect of updated technologies and guidelines on cervical cancer incidence and the critical role clinicians play in reducing the burden of disease.
HPV Vaccination
HPV vaccination has been shown to decrease cervical cancer by 90% or more among those who were vaccinated in early adolescence.3,4 The goal of vaccination is to prevent HPV infection, the first and critical step in the development of cervical cancer, as well as HPV-associated oropharyngeal, vaginal, vulvar, and anal cancers. After the HPV vaccine was introduced worldwide in 2006, robust evidence accumulated that vaccination leads to approximately 90% reductions in oncogenic HPV infections, precancers, and cancers.3-5
The HPV vaccine works by preventing infection with the seven most aggressive oncogenic HPV types.6,7 Importantly, vaccination must occur before infection to be effective. Population-level evidence from several countries demonstrates near elimination of cervical cancer before 30 years of age among women who received the vaccine in early adolescence (age 15 years or younger).3 However, vaccination at later ages is associated with reduced effectiveness.
In the United States, HPV vaccination is routinely recommended at ages 9 to 12 years, with catch-up vaccination through age 26 years.7 Two doses currently are recommended for those aged 9 to 15 years, and three doses for older individuals. However, newer data indicate substantial protection against cervical precancer from only one dose, and a one-dose option has been adopted by the World Health Organization.8,9 Although HPV vaccination also is available for adults aged 27 to 45 years, most individuals have been exposed to HPV by this time; therefore, the public health benefits are limited.4,7 However, there may be benefit to vaccination of individuals following treatment for cervical precancer.10
Screening
For adults who are past the age of routine vaccination, screening for and treating precancerous changes in cervical cells is the most effective method of cervical cancer prevention.1 The development of a detectable precancer and the progression to invasive cancer often takes several years, allowing time for detection by screening.
Cervical cytology (Papanicolau or Pap testing) was the mainstay of screening programs from 1950-2000, and was associated with an 80% reduction in cervical cancer incidence and mortality.1 However, cytology has a false-negative rate of up to 30% at each screen and, therefore, requires frequent repetition.1
The introduction of cervicovaginal HPV testing into screening approximately 20 years ago represented an advance in screening, since HPV testing can detect infection before precancerous changes are obvious and is 90% sensitive for detecting precancer.11 Because HPV testing has more favorable characteristics for a screening test than cytology (i.e., higher sensitivity), it has become the cornerstone of most screening programs.12,13
HPV testing also can be performed without a speculum when a patient collects their own vaginal sample (self-collection), which can further expand screening access.14 An HPV-negative result is extremely reassuring, since the risk of developing a precancer or cancer in the subsequent five years is approximately one in 1,000 people.15 However, between 10% and 20% of people will test positive on an HPV screening test and require enhanced follow-up.16 This is a considerably larger portion of the screening population compared to cervical cytology, after which approximately 5% require enhanced follow-up.11
Follow-Up After a Positive Screening Test
The addition of HPV testing, the change from annual to three- or five-year intervals for routine screening, and the implementation of risk-based management created a new category of patients — those under surveillance. Previous guidelines recommended colposcopy for abnormal cytology results and one-year follow-up for all negative results. With current guidelines, management options at each screening timepoint include treatment, colposcopy, repeat testing in one year, repeat testing in three years, or routine screening in five years.
Following a positive HPV test result or abnormal Pap test, patients, on average, require a minimum of seven years of enhanced screening before returning to routine intervals. Following treatment for precancer (cervical intraepithelial neoplasia [CIN] 2+ or histologic high-grade squamous intraepithelial lesion [HSIL]), this period is a minimum of 25 years.
The enhanced screening or surveillance period includes one to three years of annual testing, followed by six to 21 years of testing at three-year intervals. In addition, patients with human immunodeficiency virus (HIV) or immunosuppression require enhanced screening. Thus, approximately one in five patients in a screening population will need screening at one- or three-year intervals (if HPV testing is used) or annual (if cytology alone is used).
Positive HPV results can be triaged using cytology, p16/Ki67 dual stain, or genotyping. Colposcopy is recommended when the risk of detecting CIN3+ is 4% or higher. This occurs in several scenarios: HPV 16 or 18 is present, p16/Ki67 dual stain results are positive, or cytology results are atypical squamous cells of undetermined significance (ASC-US) or higher (noting that the risk of an ASC-US result may be modified by prior HPV-negative results).
In contrast, colposcopy can be deferred and screening performed again in one year in the following scenarios: HPV 59/56/66 but no other HPV types are present, p16/Ki67 dual stain results are negative, or cytology results are negative. In the case of a clinician-collected sample, defined as specimen collection from the cervix on speculum examination, any of the tests noted earlier can be performed by the laboratory. In the case of HPV self-collection, genotyping can be performed from the vaginal sample, but additional triage using cytology or p16/Ki67 dual stain will require the collection of a new sample from the cervix by a clinician. (See Tables 1 and 2.)
Table 1. Management of Negative Screening Test Results |
Pap Test Negative
Self-Collected Vaginal HPV Test Negative
Clinician-Collected Cervical HPV Test Negative
|
HPV: human papillomavirus; LEEP: loop electrosurgical excision procedure aMore detailed information is available for providers at asccp.org and for patients at cervicalrisk.com |
Table 2. Management of Positive Screening Test Results |
HPV16+b
HPV18+b
Pap HSILc
Pap ASC-H or AGCc
HPV Other Types:d Pap NILM
HPV Other Types:d Pap ASC-US or LSIL
HPV Other Types: Dual Stain Negative
HPV Other Types:d Dual Stain Positive
HPV 59/56/66+ and Negative for Other Typese
|
HPV: human papillomavirus; LEEP: loop electrosurgical excision procedure; ASC-H: atypical squamous cells, cannot rule out high grade squamous intra-epithelial lesion; AGC: atypical glandular cells; HSIL: high-grade squamous intraepithelial lesion; NILM: negative for intraepithelial lesion or malignancy; ASC-US: atypical squamous cells of undetermined significance; LSIL: low-grade squamous intraepithelial lesion; CIN: cervical intraepithelial neoplasia bThe management is the same whether the result is obtained via self-collection or clinician collection, and whether there are accompanying Pap or dual stain results other than those specifically mentioned. cThe management is the same whether or not there are accompanying HPV test or dual stain results other than those specifically mentioned. dThe management for “other” HPV types cannot be determined without a Pap or dual stain. Note that a speculum exam is needed to collect a Pap or dual stain if the HPV test was a self-collection. ePap or dual stain results are not needed for management of HPV types 59/56/66. If obtained, repeat in one year is recommended for dual stain-positive or -negative, and for Pap results of NILM, ASC-US, or LSIL. Colposcopy is recommended for Pap results of ASC-H, AGC, or HSIL. |
Colposcopy
The addition of HPV testing, the change from annual to three- or five-year intervals for routine screening, and the implementation of risk-based management substantially reduces the number of colposcopies while simultaneously increasing their acuity. The goal of risk-based management is to focus care on those patients with precancer (defined as CIN grade 2 or 3 [CIN2 or CIN3] or histologic HSIL). Specifically, guidelines recommend more testing and treatment among those with a high risk of CIN3+ and avoiding colposcopy and biopsy among those with lower risk.
The result of increased screening intervals and fewer situations in which colposcopy is recommended is a dramatic decrease in total colposcopy referrals and a higher acuity among those referred. Colposcopists should expect to see a higher proportion of patients with CIN2 or higher among their referral populations. Because of this, taking an adequate number of biopsies (two to four for most patients) is critical for precancer detection.17 This reduction in unnecessary procedures (defined as those that do not detect CIN2+) is a direct result of recommendations to defer colposcopy among low-risk patients. If guidelines are functioning as expected, lower rates of colposcopy should not result in missed precancer or cancer, since high-risk patients are referred for biopsy while low-risk patients are deferred.
Summary
The past 20 years have seen many advances in cervical cancer prevention. HPV vaccination has demonstrated 90% cancer reductions, raising the possibility of future generations being free from cervical cancer. Screening remains the mainstay of prevention for the current generation of adult women.
The addition of HPV testing to screening increases precancer detection at each screening round, allowing for longer intervals between tests. Risk-based screening and management focuses testing and invasive procedures on those at highest risk of precancer, which has the potential to both decrease cancer and to decrease overtesting and overtreatment. However, newer guidelines are complex, and they create a new patient population that requires enhanced screening at one- or three-year intervals.
Improved systems are needed to routinely assess patients to determine whether they require enhanced screening as well as to track those needing colposcopy, since patients referred for colposcopy under current guidelines are at higher risk of precancer than those referred in the past. At the core of prevention is access to vaccination, screening, follow-up, and treatment, since the majority of cancers occur in those who are unvaccinated, underscreened, or never treated following an abnormality.18
Rebecca B. Perkins, MD, MSc, is Professor, Department of Obstetrics and Gynecology, Tufts University School of Medicine/Tufts Medical Center, Boston.
References
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9. World Health Organization. One-dose human papillomavirus (HPV) vaccine offers solid protection against cervical cancer. Published April 11, 2022. https://www.who.int/news/item/11-04-2022-one-dose-human-papillomavirus-(hpv)-vaccine-offers-solid-protection-against-cervical-cancer
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15. Perkins RB, Guido RS, Castle PE, et al. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis. 2020;24(2):102-131.
16. Lee YW, Morgan JR, Fiascone S, Perkins RB. Underscreening, overscreening, and guideline-adherent cervical cancer screening in a national cohort. Gynecol Oncol. 2022;167(2):181-188.
17. Wentzensen N, Schiffman M, Silver MI, et al. ASCCP colposcopy standards: Risk-based colposcopy practice. J Low Genit Tract Dis. 2017;21(4):230-234.
18. Benard VB, Jackson JE, Greek A, et al. A population study of screening history and diagnostic outcomes of women with invasive cervical cancer. Cancer Med. 2021;10(12):4127-4137.