This Research Letter summarizes all updates to the 2019 Guidelines through September 2023, including: endorsement of the 2021 Opportunistic Infections guidelines for HIV+ or immunosuppressed patients; clarification of use of human papillomavirus testing alone for patients undergoing observation for cervical intraepithelial neoplasia 2; revision of unsatisfactory cytology management; clarification that 2012 guidelines should be followed for patients aged 25 years and older screened with cytology only; management of patients for whom colposcopy was recommended but not completed; clarification that after treatment for cervical intraepithelial neoplasia 2+, 3 negative human papillomavirus tests or cotests at 6, 18, and 30 months are recommended before the patient can return to a 3-year testing interval; and clarification of postcolposcopy management of minimally abnormal results.

CONTEXT.—: Lower Anogenital Squamous Terminology (LAST) standardization recommended p16(INK4a) immunohistochemistry (p16 IHC) for biopsies diagnosed morphologically as cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) to classify them as low-grade or high-grade squamous intraepithelial lesions (HSILs). OBJECTIVE.—: To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses. DESIGN.—: A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available. RESULTS.—: Biopsies were more likely to test p16 IHC positive with increasing severity of CP diagnoses, overall (P(trend) ≤ .001) and within each HPV risk group (P(trend) ≤ .001 except for low-risk HPV [P(trend) < .010]). All abnormal grades of CP-diagnosed biopsies were more likely to test p16 IHC positive with a higher HPV risk group (P(trend) < .001), and testing p16 IHC positive was associated with higher HPV risk group than testing p16 IHC negative for each grade of CP-diagnosed biopsies (P < .001). p16 IHC-positive, CP-diagnosed CIN2 biopsies were less likely than CP-diagnosed CIN3 biopsies to test HPV16 positive, have an antecedent HSIL(+) cytology, or to be diagnosed as CIN3(+) by the EP (P < .001 for all). p16 IHC-positive, CP-diagnosed CIN1 biopsies had lower HPV risk groups than p16 IHC-negative, CP-diagnosed CIN2 biopsies (P < .001). CONCLUSIONS.—: p16 IHC-positive, CP-diagnosed CIN2 appears to be lower cancer risk than CP-diagnosed CIN3. LAST classification of "HSIL" diagnosis, which includes p16 IHC-positive CIN2, should annotate the morphologic diagnosis (CIN2 or CIN3) to inform all management decisions, which is especially important for young (<30 years) women diagnosed with CIN2 for whom surveillance rather than treatment is recommended.

BACKGROUND: Racial and ethnic variations in attribution of cervical precancer and cancer to HPV types may result in different HPV vaccine protection, screening test coverage, and clinical management. METHODS: Pooling data from seven U.S. studies, we calculated the proportional attribution of precancers and cancers to HPV types using HPV DNA typing from diagnosis. All statistical tests were 2-sided. RESULTS: For all racial and ethnic groups, most cervical intraepithelial neoplasia grade 3 (CIN3) (n=5,526) and squamous cell carcinoma (SCC) cases (n=1,138) were attributed to types targeted by the 9-valent vaccine. A higher proportion of CIN3s were attributed to non-vaccine HPV types among non-Hispanic Black women (15.8%) compared with non-Hispanic Asian or Pacific Islander (9.7%, P=.002), non-Hispanic White (9.2%, P<.001), and Hispanic women (11.3%, P=.004). The proportion of SCCs attributed to 9-valent types was similar by race and ethnicity (90.4%-93.8%, P=.80). A higher proportion of CIN3s were attributed to non-vaccine HPV35 among non-Hispanic Black (9.0%) compared with non-Hispanic Asian or Pacific Islander (2.2%), non-Hispanic White (2.5%), and Hispanic women (3.0%, all P<.001). Compared with CIN3, the proportion of SCCs attributed to HPV35 among Non-Hispanic Black women (3.2%) was lower and closer to other groups (0.3%-2.1%, P=.70). CONCLUSION: The 9-valent HPV vaccine will prevent nearly all cervical precancers and invasive cancers among major racial and ethnic groups in the United States. Adding HPV35 to vaccines could prevent a small percentage of CIN3s and SCCs, with greater potential impact for CIN3s among Black women. HPV screening tests target high-risk HPV types, including HPV35. Future genotyping triage strategies could consider the importance of HPV35 and other HPV16 related types.

The 2019 ASCCP Risk-Based Management Consensus Guidelines represent a paradigm shift from using primarily results-based algorithms to using risk-based management based on a combination of current screening test results and past screening history. Screening using HPV testing or HPV/cytology co-testing provides superior risk stratification compared to cytology alone. Therefore, incorporating HPV testing into risk stratification and recommendations for surveillance following abnormal results was an important part of the 2019 guidelines. While the 2019 guidelines provide management recommendations for most results, certain situations do not have specific guidance. In such cases, using the 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors is acceptable. For individuals aged 25 or older screened with cytology alone, the 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors are recommended for management of abnormal results. Specifically, the 2012 guidelines recommend colposcopy for all cytology results of low grade squamous intraepithelial lesion (LSIL) or higher for individuals aged 25 and above.

Importance: A substantial effect of human papillomavirus (HPV) vaccines on reducing HPV-related cervical disease is essential before modifying clinical practice guidelines in partially vaccinated populations. Objective: To determine the population-based cervical intraepithelial neoplasia (CIN) trends when adjusting for changes in cervical screening practices that overlapped with HPV vaccination implementation. Design, Setting, and Participants: The New Mexico HPV Pap Registry, which captures population-based estimates of both cervical screening prevalence and CIN, was used to compute CIN trends from January 1, 2007, to December 31, 2014. Under New Mexico Administrative Code, the New Mexico HPV Pap Registry, a statewide public health surveillance program, receives mandatory reporting of all cervical screening (cytologic and HPV testing) and any cervical, vulvar, and vaginal histopathological findings for all women residing in New Mexico irrespective of outcome. Main Outcome Measures: Prespecified outcome measures included low-grade CIN (grade 1 [CIN1]) and high-grade CIN (grade 2 [CIN2] and grade 3 [CIN3]). Results: From 2007 to 2014, a total of 13520 CIN1, 4296 CIN2, and 2823 CIN3 lesions were diagnosed among female individuals 15 to 29 years old. After adjustment for changes in cervical screening across the period, reductions in the CIN incidence per 100000 women screened were significant for all grades of CIN among female individuals 15 to 19 years old, dropping from 3468.3 to 1590.6 for CIN1 (annual percentage change [APC], -9.0; 95% CI, -12.0 to -5.8; P < .001), from 896.4 to 414.9 for CIN2 (APC, -10.5; 95% CI, -18.8 to -1.2; P = .03), and from 240.2 to 0 for CIN3 (APC, -41.3; 95% CI, -65.7 to 0.3; P = .05). Reductions in the CIN2 incidence were also significant for women 20 to 24 years old, dropping from 1027.7 to 627.1 (APC, -6.3; 95% CI, -10.9 to -1.4; P = .02). Conclusions and Relevance: Population-level decreases in CIN among cohorts partially vaccinated for HPV may be considered when clinical practice guidelines for cervical cancer screening are reassessed. Evidence is rapidly growing to suggest that further increases in raising the age to start screening are imminent, one step toward integrating screening and vaccination.

BACKGROUND: Cervical screening consumes substantial resources, but little is known about utilization in the United States or compliance with guideline recommendations. METHODS: To describe population screening coverage, utilization, and outcomes and examine time trends from 2008 to 2011, cervical cytology reports from women residing in New Mexico (981,063 tests from 511,381 women) were evaluated. RESULTS: From 2008 to 2011 cervical screening utilization decreased at all ages, but especially in younger women, with a two-third reduction at ages 15 to 20 years. Ninety-four percent of women ages 25 to 29 years were screened within 48 months but coverage decreased at older ages to 69% at 45 to 49 years and 55% at 60 to 64 years. Intervals between screening tests were significantly longer in 2011 compared with 2008 [HR = 1.23; 95% confidence intervals (CI), 1.22-1.24], although the commonest rescreening interval was 13 months. In 2011, 91.9% of screening tests for women ages 21 to 65 years were negative, 6.6% showed minor abnormalities, and 1.0% high-grade abnormalities. High-grade abnormality rates were relatively constant over time, but minor abnormalities and atypical cells cannot rule out high-grade (ASC-H) were increasing. CONCLUSIONS: This population-based evaluation of cervical screening shows high coverage under the age of 40 years, but lower levels in older women. Screening under age 21 years is becoming less common and screening intervals are lengthening, reflecting updates in national screening guidelines. IMPACT: Assessment of cervical screening intervals and population outcomes is essential for accurately estimating the impact and effectiveness of changing recommendations and vaccination against human papilloma virus infections.

OBJECTIVE: All national organizations now recommend that women be screened for cervical cancer beginning at age 21 years, regardless of age of sexual initiation; however, studies have shown that providers continue to screen much earlier than recommended. Two federal cancer surveillance systems were used to quantify the burden of invasive cervical carcinoma among women younger than 40 years of age. METHODS: We examined combined data from the National Program of Cancer Registries and the Surveillance, Epidemiology, and End Results Program covering 92% of the U.S. population. We calculated the age-adjusted incidence of cervical carcinoma among women younger than age 40 years by age, race, ethnicity, and histology for the time period of 1999-2008. RESULTS: For women younger than age 40 years, 78% of the cervical cancer cases were diagnosed in women aged 30-39, 21% were diagnosed in women 20-29 years of age, and 1% was diagnosed in women younger than age 20 years. There was an average of 3,063 cases of invasive cervical carcinomas annually from 1999 through 2008, with an average of 14 carcinomas per year (rate of 0.15 per 100,000 females) among those aged 15-19 years, and 125 carcinomas per year (rate of 1.4 per 100,000 females) among those aged 20-24 years. CONCLUSION: Cervical cancer is very rare in young women. Widespread implementation of Pap testing over the past four decades has detected very few cases of cervical cancer in women younger than 25 while potentially causing harm with unnecessary follow-up interventions. LEVEL OF EVIDENCE: III.