Calendar-period trends in cervical precancer and cancer diagnoses since the introduction of human papillomavirus and cytology co-testing into routine cervical cancer screening at Kaiser Permanente Northern California.

OBJECTIVES: The longer-term impact of introducing human papillomavirus (HPV) testing into routine cervical cancer screening on precancer and cancer rates by histologic type has not been well described. Calendar trends in diagnoses were examined using data from Kaiser Permanente Northern California, which introduced triennial HPV and cytology co-testing in 2003 for women aged ≥30 years. METHODS: We examined trends in cervical precancer (cervical intraepithelial neoplasia grade 3 [CIN3] and adenocarcinoma in situ [AIS]) and cancer (squamous cell carcinoma [SCC] and adenocarcinoma [ADC]) diagnoses per 1000 screened during 2003-2018. We examined ratios of squamous vs. glandular diagnoses (SCC:ADC and CIN3:AIS). RESULTS: CIN3 and AIS diagnoses increased approximately 2% and 3% annually, respectively (ptrend < 0.001 for both). While SCC diagnoses decreased by 5% per annually (ptrend < 0.001), ADC diagnoses did not change. These patterns were generally observed within each age group (30-39, 40-49, and 50-64 years). ADC diagnoses per 1000 screened did not change even among those who underwent co-testing starting in 2003-2006. SCC:ADC decreased from approximately 2.5:1 in 2003-2006 to 1.3:1 in 2015-2018 while the CIN3:AIS remained relatively constant, ∼10:1. CONCLUSIONS: Since its introduction at KPNC, co-testing increased the detection of CIN3 over time, which likely caused a subsequent reduction of SCC. However, there has been no observed decrease in ADC. One possible explanation for lack of effectiveness against ADC is the underdiagnosis of AIS. Novel strategies to identify and treat women at high risk of ADC need to be developed and clinically validated.

Retrospective analysis of negative cytology results correlated with a positive high-risk in the human papillomavirus result and subsequent results of patients over a period of three years.

This research paper evaluates the efficacy of co-testing in precluding cervical cancer, with a particular focus on distinguishable outcomes of the human papillomavirus (HPV) vs. cytology tests. A retrospective review of 5948 patients, who tested positive for high-risk HPV but showed negative cytologic findings, revealed that 15.006% tested positive in subsequent screenings. A comparative analysis of various commercial HPV tests highlighted the precision of mRNA-based HPV testing by Aptima (Hologic) in reducing the likelihood of false-negative cytology. The paper challenges the conviction that a negative cytology alone suffices advocating for a condensed testing interval in instances of positive HPV outcomes, thereby facilitating earlier intervention and optimal preventive care. These findings unveil an exigency for reconsidering preventive strategies based on test outcomes.

Evaluation of co-testing with cytology and human papillomavirus testing in cervical screening.

Cervical screening is increasingly switching to human papillomavirus (HPV) testing. In many settings, the switch has involved one or several co-tests (testing using both cytology and HPV) in the screening guidelines, to ensure safety. When Sweden switched to HPV testing in 2015 the guidelines included a co-test at age 41. To evaluate the effect of co-testing, we identified all 208,701 women resident in Sweden who in 2019 were 40-42 years old and thus eligible for co-testing. All cervical samples, the results of the test and of the subsequent biopsies were identified in the Swedish National Cervical Screening Registry. Out of the 10,643 women with co-testing in screening, there were 197 women with a subsequent biopsy with high-grade cervical neoplasia or worse (CIN2+). Among these 197 women, 189 had a screening test positive for both HPV and cytology, 6 women were HPV+/Cyt- and 2 women were HPV-/Cyt+. There were 7115 women with a co-test outside of the screening program. Among these, 325 women had a CIN2+ in histopathology, 290 were double positive, 13 women were cyt+/HPV-, and 11 women each were HPV+/cyt- and HPV-/Cyt-. In summary, the additional yield of CIN2+ with co-testing was 2 cases per 10,643 women as compared with 195/10,643 CIN2+ cases detected with HPV screening alone. However, for cervical samples taken outside the screening program (e.g. taken on a clinical indication) there was an increased yield (314 CIN2+ cases detected with co-testing as compared to 301 cases with HPV screening).

Underscreening, overscreening, and guideline-adherent cervical cancer screening in a national cohort.

OBJECTIVE: To explore rates of under- and overscreening for cervical cancer among a national cohort. METHODS: The MarketScan database, a national administrative database of employee-sponsored insurance, was queried for elements relevant to cervical cancer screening among women aged 21-65 with 6 years of continuous enrollment (2015-2019). Average-risk women were defined as those without high-risk medical conditions or abnormal screening histories, and without evidence of hysterectomy with removal of the cervix for benign indications. Average-risk women were considered adequately screened if they had Pap tests alone at 2.5-3.5 year intervals, or HPV tests or co-tests at 4.5-5.5 year intervals. Logistic regressions were used to predict the odds of receiving guideline-adherent screening, underscreening, and overscreening. RESULTS: Among 1,872,809 eligible patients, 1,471,063 (78.5%) qualified for routine screening. Of these, only 18.1% received guideline-adherent screening, and 25.4% were unscreened during the 6-year period. Younger women (aged 21-39) were more likely to be overscreened [OR 1.46]. Older women (aged 50-64) were more likely to be underscreened or unscreened during the study period [OR 2.54]. Guideline-adherent screening was highest with HPV testing alone (80%) followed by co-testing (44%), and lowest with cytology alone (15%). A total of 329,062 women in this general population sample (18%) met high-risk criteria that required increased frequency of screening. CONCLUSIONS: High rates of both underscreening and overscreening indicate a need for additional strategies to improve guideline-adherent care. CLINICAL TRIAL REGISTRATION: N/A.

Cost-effectiveness analysis of the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines for the management of abnormal cervical cancer screening tests and cancer precursors.

BACKGROUND: The guidelines for managing abnormal cervical cancer screening tests changed from a results-based approach in 2012 to a risk-based approach in 2019. OBJECTIVE: We estimated the cost-effectiveness of the 2019 management guidelines and the changes in resource utilization moving from 2012 to 2019 guidelines. STUDY DESIGN: We utilized a previously published model of cervical cancer natural history and screening to estimate and compare the lifetime costs and the number of screens, colposcopies, precancer treatments, cancer cases, and cancer deaths associated with the 2012 vs 2019 management guidelines. We assessed these guidelines under the scenarios of observed screening practice and perfect screening adherence to 3-year cytology starting at age 21, with a switch to either 3-year or 5-year cytology plus human papillomavirus cotesting at age 30. In addition, we estimated the lifetime costs and life years to determine the cost-effectiveness of shifting to the 2019 management guidelines. RESULTS: Under the assumptions of both observed screening practice and perfect screening adherence with a strategy of 3-year cytology at ages 21 to 29 and switching to 3-year cotesting at age 30, the management of the screening tests according to the 2019 guidelines was less costly and more effective than the 2012 guidelines. For 3-year cytology screening at ages 21 to 29 and switching to 5-year cotesting at age 30, the 2019 guidelines were more cost-effective at a willingness-to-pay threshold of $100,000 per life year gained. Across all scenarios, the 2019 management guidelines were associated with fewer colposcopies and cancer deaths. CONCLUSION: Our model-based analysis suggests that the 2019 guidelines are more effective overall and also more cost-effective than the 2012 guidelines, supporting the principle of "equal management of equal risks."

Co-testing in cervical screening among 40- to 42-year-old women is unreasonable.

INTRODUCTION: The screening program for cervical cancer in Sweden recommends the use of primary human papillomavirus (HPV) screening for women aged ≥30 to 65 years. Co-testing with both HPV analysis and cytology is recommended at the first screening after the age of 40 years. To fulfil co-testing, all screened women aged 40-42 years within the region of Skåne were co-tested. The aim of the audit was to investigate the proportion of severe dysplasia as diagnosed by cytology and histological follow-up among women with Aptima HPV-negative tests. We also calculated the cost of adding the cytology to the HPV primary screening program. MATERIAL AND METHODS: The local cytology registry was used to identify women aged 40-42 years who attended screening and were co-tested during the 4 years from January 2017 to December 2020. The Aptima HPV messenger RNA assay detects 14 HPV types. For Aptima HPV-negative women with high-grade cytology or histological high-grade squamous intraepithelial lesions (HSILs), we performed extended HPV typing for 40 HPV types with polymerase chain reaction using modified GP5+/6+ primers followed by a Luminex assay. To estimate the added cost of using cytology to identify each histologically confirmed cervical HSIL case among Aptima HPV-negative women, we used the current cost of €21.2 per cytology evaluation at our laboratory. RESULTS: Of 19 599 women, 5.8% (1137/19 599) had abnormal cytology. Among Aptima HPV-negative women, 0.11‰ (2/18 132) had histologically confirmed HSIL. One of the women was infected with HPV18 and the other with HPV73 at the diagnosis of HSIL. The calculated cost to find one HSIL, by adding cytology to HPV-negative cases, was approximately €200 000. CONCLUSIONS: The clinical benefit of a single cytology co-test added to an HPV-based screening program in women aged 40-42 years appears doubtful and economically unreasonable.

Eligibility for cervical cancer screening exit: Comparison of a national and safety net cohort.

OBJECTIVE: To determine eligibility for discontinuation of cervical cancer screening. METHODS: Women aged 64 with employer-sponsored insurance enrolled in a national database between 2016 and 2018, and those aged 64-66 receiving primary care at a safety net health center in 2019 were included. Patients were evaluated for screening exit eligibility by current guidelines: no evidence of cervical cancer or HIV-positive status and no evidence of cervical precancer in the past 25 years, and had evidence of either hysterectomy with removal of the cervix or evidence of fulfilling screening exit criteria, defined as two HPV screening tests or HPV plus Pap co-tests or three Pap tests within the past 10 years without evidence of an abnormal result. RESULTS: Of the 590,901 women in the national claims database, 131,059 (22.2%) were eligible to exit due to hysterectomy (1.6%) or negative screening (20.6%). Of the 1544 women from the safety net health center, 528 (34.2%) were eligible to exit due to hysterectomy (9.3%) or negative screening (24.9%). Most women did not have sufficient data available to fulfill exit criteria: 382,509 (64.7%) in the national database and 875 (56.7%) in the safety net hospital system. Even among women with 10 years of insurance claims data, only 41.5% qualified to discontinue screening. CONCLUSIONS: Examining insurance claims in a national database and electronic medical records at a safety net institution led to remarkably similar findings: two thirds of women fail to qualify for screening exit. Additional steps to ensure eligibility prior to screening exit may be necessary to decrease preventable cervical cancers among women aged >65. CLINICAL TRIAL REGISTRATION: N/A.

Clinical follow-up practices after cervical cancer screening by co-testing: A population-based study of adherence to U.S. guideline recommendations.

Failure to follow-up women after abnormal cervical screening could lead to cervical cancers, yet little is known about adherence to recommended follow-up after abnormal co-testing [cytology and high-risk human papillomavirus (hrHPV) testing]. We documented clinical management following cervical screening by co-testing in a diverse population-based setting. A statewide surveillance program for cervical screening, diagnosis, and treatment was used to investigate all cytology, hrHPV and biopsy reports in the state of New Mexico from January 2015 through August 2019. Guideline-adherent follow-up after co-testing required 1) biopsy within 6 months for low-grade cytology if positive for hrHPV, for high-grade cytology irrespective of hrHPV, and for HPV 16/18 positive results irrespective of cytology and; 2) repeat co-testing within 18 months if cytology was negative and hrHPV test was positive (excluding types 16/18). Screening co-tests (2015-2017) for 164,522 women were analyzed using descriptive statistics, Kaplan Meier curves, and pairwise comparisons between groups. Guideline adherence was highest when both cytology and hrHPV tests were abnormal, ranging from 61.7% to 80.3%. Guideline-adherent follow-up was lower for discordant results. Women with high-grade cytology were less likely to receive a timely biopsy when hrHPV-testing was negative (48.1%) versus positive (83.3%) (p < 0.001). Only 47.9% of women received biopsies following detection of HPV16/18 with normal cytology, and 30.8% received no follow-up within 18-months. Among women with hrHPV-positive normal cytology without evidence of HPV 16/18 infection, 51% received no follow-up within 18 months. Provider education and creation of robust recall systems may help ensure appropriate follow-up of abnormal screening results.

Iranian women's psychological responses to positive HPV test result: a qualitative study.

BACKGROUND: Human papillomavirus testing as an established screenings test allow for the early detection and treatment of cervical cancer. Testing positive for HPV may have adverse consequences for women. This study aimed to explore the psychological impacts of testing positive for HPV on women in a developing country with a distinct cultural and religious background. METHODS: Qualitative face-to-face semi-structured interviews were conducted with 40 Iranian women who received a positive high-risk HPV result. Content analysis approach was used to data analysis through MAXQDA10. RESULTS: Three main categories were emerged: initial confrontation; STD-related psychological burden; and rebuilding health. Initial reactions to positive HPV results were shock, unrealistic fear, confusion, distress, and financial concerns. Stigma was manifested in form of self-blame, fear of HPV-disclosure, negative body image, being stigmatized by healthcare providers, and receiving health care anonymously. Refusal to use insurance services showed how evident and powerful the stigma was. Most women reported lifestyles and sexual behaviors modifications to help their immune system to clear HPV; indicating that the screening can work as a valuable opportunity to improve women's physical and sexual health. Regular follow-up, safe sex and a focus on spirituality enable women infected with HPV to take control of the situation. Worrying about other HPV-linked cancers (oropharynx and anal) and fears of partner infection indicated that women consider HPV to be more than just a cause of cervical cancer. CONCLUSIONS: The findings implied to the HPV-positive women's need to support and factual information. Designing and implementing interventions that mitigate the psychological effect of positive HPV test results can highlight the potential benefits of screening for women's health.

Primary HPV testing with cytology versus cytology alone in cervical screening-A prospective randomized controlled trial with two rounds of screening in a Chinese population.

We conducted a prospective randomized controlled trial with two screening rounds to evaluate the effectiveness of combining HPV testing with liquid-based cytology (LBC) as a co-test, compared to LBC only in cervical cancer screening of a Chinese population. First, 15,955 women aged 30-60 were randomized at a 1:1 ratio into an intervention group (Digene Hybrid Capture 2 HPV test with LBC) and a control group (LBC alone). Women in the intervention group would be referred for colposcopy and biopsy immediately if they were found to have high-risk HPV regardless of cytology results. The detection of cervical intraepithelial neoplasia grade 2 or above (CIN2+) lesions was significantly higher in the intervention group compared to the control (0.95% vs. 0.38%, OR 2.50, 95% CI 1.65-3.88). At the subsequent round of screening approximately 36 months later, CIN2+ detection was significantly lower in the intervention group (0.08% vs. 0.35%, OR 0.23, 95% CI 0.08-0.57). Over the two rounds of screening, the total detection of CIN2+ was higher in the intervention group (1.01% vs. 0.66%, OR 1.53, 95% CI 1.09-2.19). There was a fourfold increase (10.6% vs. 2.4%, p < 0.001) in the number of colposcopies performed in the intervention arm. Adding a high-risk HPV test to cytology for primary cervical screening led to earlier detection of clinically significant preinvasive lesions, resulting in a reduced detection of CIN2+ lesions in subsequent rounds and an increased rate of colposcopy.

Outcomes of prior cervical cytology and HR-HPV testing in women subsequently diagnosed with CIN1, CIN2/3, and invasive cervical cancer: a 4-year routine clinical experience after implementation of systematic training and quality control programs.

BACKGROUND: In 2013, Jinan KingMed Diagnostics (JKD) first established a systematic cervical cytology training and quality control (QC) program in Shandong Province, China. We compared the efficacy of high-risk human papillomavirus (HR-HPV) detection, cytology, and their combination in routine clinical practice after the implementation of the training and QC program to identify the optimal first-line screening method in this region. METHODS: The data of patients histologically diagnosed with cervical intraepithelial neoplasia (CIN) 1, CIN2/3, and invasive cervical cancer (ICC) between January 2014 and December 2017 were retrieved from the JKD database. Cytology and/or HR-HPV testing results within 3 months preceding the CIN1 diagnoses and 6 months preceding the CIN2/3 and ICC diagnoses were analyzed. RESULTS: Prior screening data were available for 1829 CIN1 patients, 2309 CIN2/3 patients, and 680 ICC patients. Cytology alone and HR-HPV testing alone had similar rates of positive results for CIN2/3 (97.2% [854/879] vs. 95.4% [864/906], P = 0.105) and ICC detection (89.1% [205/230] vs. 92.7% [204/220], P = 0.185). Compared with either method alone, co-testing slightly increased the screening sensitivity for CIN2/3 (99.8% [523/524], all P < 0.001) and ICC (99.6% [229/230], all P < 0.001) detection. In the CIN1 group, cervical cytology alone (92.9% [520/560]) was more sensitive than HR-HPV testing alone (79.9% [570/713], P < 0.001), and co-testing (95.3% [530/556]) did not significantly improve the screening sensitivity (P = 0.105). CONCLUSIONS: After the implementation of a systematic training and QC program, both cytology and HR-HPV testing may be adopted for primary cervical cancer screening in Shandong Province.

Recurrent post-coital bleeding: Should colposcopy still be mandatory?

BACKGROUND: Colposcopy has been recommended for all women with recurrent post-coital bleeding (PCB) even if their cervical cytology or co-test (involving oncogenic human papillomavirus (HPV) DNA testing and cytology) are negative. AIMS: To determine the risk of cervical cancer and its precursors among women with recurrent PCB with negative cytology or co-test. MATERIALS AND METHODS: A retrospective analysis of two cohorts of women with PCB referred to a tertiary colposcopy clinic. Cohort (1) (n = 1846) between 1 January 2000 and 31 December 2016 (cytology-based screening) and Cohort (2) (n = 215) from 1 January 2018 to 31 December 2019 after introduction of primary HPV screening. RESULTS: In 1217 (65.9%) women in Cohort (1) referred with negative cytology, there was one cancer (0.08%) and 22 high-grade squamous intraepithelial lesions (HSIL (cervical intraepithelial neoplasia 2/3)) on histopathology. In Cohort (2), there was no cancer or HSIL in 83 women with negative co-tests (negative for oncogenic HPV and cytology). False-negative cytology after a negative referral cytology or co-test was low with 2% of repeat cytology at initial colposcopy showing possible HSIL or worse. CONCLUSIONS: Women presenting with PCB and negative cytology alone have a low risk of cancer and could have HPV testing before being triaged to colposcopy. We showed that with the assurance of a negative co-test and the low likelihood of false-negative cytology, these women could avoid colposcopy unless cervical cancer is clinically suspected. There is a need for a larger cohort study to substantiate our findings with more precision.

Prior cervical cytology and high-risk HPV testing results for 311 patients with invasive cervical adenocarcinoma: a multicenter retrospective study from China's largest independent operator of pathology laboratories.

BACKGROUND: High-risk human papillomavirus (HR-HPV) testing is more sensitive than cytology for the detection of cervical cancer and its precursors. However, limited and inconsistent data are available about the efficacy of the combination of these two methods for screening cervical adenocarcinoma. This multicenter retrospective study investigated the screening results of a cohort of Chinese patients who were subsequently diagnosed with invasive cervical adenocarcinoma, with the goal of identifying the optimal cervical adenocarcinoma screening method. METHODS: We retrospectively retrieved and analyzed the data from patients with histologically confirmed primary invasive cervical adenocarcinoma from eight local pathology laboratories operated by KingMed Diagnostics, the largest independent operator of pathology laboratories in China, over a 2-year period. Only patients who underwent cytology and/or HR-HPV testing within 6 months before the adenocarcinoma diagnosis were included. HR-HPV DNA was detected using one of two HPV test kits: the Hybrid Capture 2 (HC2) assay (Qiagen, Hilden, Germany) and an HPV genotyping panel (Yaneng Bio, Shenzhen, China). RESULTS: Of the 311 patients, 136 underwent cytology alone, 106 underwent HR-HPV testing alone, and 69 underwent cytology and HR-HPV co-testing. The sensitivities of cytology alone (64.0, 95% confidence interval [CI]: 55.9-72.0) and HR-HPV testing alone (66.0, 95% CI: 57.0-75.1) were similar (P = 0.738). The sensitivity of cytology and HR-HPV co-testing (87.0, 95% CI: 79.0-94.9) was significantly higher than that of either cytology (P = 0.001) or HR-HPV testing alone (P = 0.002). CONCLUSIONS: Both cytology alone and HR-HPV testing alone showed poor screening efficiency, whereas the combination of the two clearly increased the efficiency of primary cervical adenocarcinoma screening. Thus, cytology and HR-HPV co-testing might be the most efficient cervical adenocarcinoma screening method.

Factors associated with high-risk human papillomavirus test utilization and infection: a population-based study of uninsured and underinsured women.

BACKGROUND: Current cervical cancer screening guidelines recommend a Pap test every 3 years for women age 21-65 years, or for women 30-65 years who want to lengthen the screening interval, a combination of Pap test and high-risk human papilloma virus testing (co-testing) every 5 years. Little population-based data are available on human papilloma virus test utilization and human papilloma virus infection rates. The objective of this study was to examine the patient-level, cervical cancer screening, and area-level factors associated with human papilloma virus testing and infection among a diverse sample of uninsured and underinsured women enrolled in the New Jersey Cancer Early Education and Detection (NJCEED) Program. METHODS: We used data for a sample of 50,510 uninsured/underinsured women, age ≥ 29 years, who screened for cervical cancer through NJCEED between January 1, 2009 and December 31, 2015. Multivariable logistic regression models were used to estimate associations between ever having a human papilloma virus test or a positive test result, and individual- (age, race/ethnicity, birthplace) and area-level covariates (% below federal poverty level, % minority, % uninsured), and number of screening visits. RESULTS: Only 26.6% (13,440) of the sample had at least one human papilloma virus test. Among women who underwent testing, 13.3% (1792) tested positive for human papilloma virus. Most women who were positive for human papilloma virus (99.4%) had their first test as a co-test. Human papilloma virus test utilization and infection were significantly associated with age, race/ethnicity, birthplace (country), and residential area-level poverty. Rates of human papilloma virus testing and infection also differed significantly across counties in the state of New Jersey. CONCLUSIONS: These findings suggest that despite access to no-cost cervical cancer screening for eligible women, human papilloma virus test utilization was relatively low among diverse, uninsured and underinsured women in New Jersey, and test utilization and infection were associated with individual-level and area-level factors.

The ideal strategy for cervical cancer screening in Japan: Result from the Fukui Cervical Cancer Screening Study.

INTRODUCTION: The aims of the Fukui Cervical Cancer Screening (FCCS) study are to determine the frequency of women with high-risk HPV (hrHPV), whether HPV16 or HPV18 (HPV16/18), in the Japanese cancer screening population for the first time and to identify the best strategy for cervical cancer screening in Japan. METHODS: This study enrolled 7584 women aged ≥25 years who were undergoing routine screening. All women underwent LBC and cobas HPV tests. Women with abnormal cytology, whether hrHPV positive or negative; women with hrHPV positivity with either normal or abnormal cytology; and women randomly selected from women with normal cytology and negative hrHPV negative were referred for colposcopy. RESULTS: The prevalences of hrHPV positivity and HPV16/18 positivity were 6.8% and 1.7%, respectively. The baseline data from the FCCS study showed that the combination of HPV tests and cytology was more sensitive than cytology with respect to the detection of intraepithelial neoplasia grade 2 or worse. However, the specificity (94.1%) of the co-testing strategy that required all women with abnormal cytology or hrHPV positivity to be referred for colposcopy was much lower than that (97.8%) of cytology. The sensitivity and specificity of the co-testing strategy that required only women with abnormal cytology or HPV16/18 positivity to undergo colposcopy were 85.5% and 97.0%, respectively. CONCLUSION: The baseline data from the FCCS study suggest that a cervical cancer screening strategy in which only women with abnormal cytology or HPV16/18 positivity undergo colposcopy offers a more balanced sensitivity and specificity than other strategies.

Primary HPV testing: a proposal for co-testing in initial rounds of screening to optimise sensitivity of cervical cancer screening.

As explained by Kitchener in a previous issue of Cytopathology (2015;26:4-6), primary human papillomavirus (HPV) testing is likely to be introduced in the UK for all women aged 25-64 years following pilot site studies already in place. This will be necessary when the prevalence of cervical cancer and its precursors declines when vaccination takes effect but there is a risk in abandoning cytology as a primary test: a risk that would be most apparent in the present unvaccinated population in which the prevalence of cervical cancer and its precursors is exceptionally high. HPV testing is more sensitive than cytology but has a significant false-negative rate that could be detrimental to a successful screening programme if introduced without cytology backup. Accurate cytology would be needed for triage and could be compromised if HPV-negative tests were excluded from examination. This article proposes a compromise: cytology and HPV co-testing for the first two screening tests to optimise the sensitivity of the test as a whole. Registrations of invasive and in situ carcinoma of the uterine cervix in England indicate that the prevalence of the disease is highest in young women in the early rounds of screening. Calculations of the likely impact on the workload of this proposal have been based on a service evaluation of 295 cytology tests received at St Thomas' Hospital, which suggests that the volume of cytology tests would be reduced by approximately 60% compared with 80% for primary HPV testing alone. This proposal should be debated openly before irrevocable changes are made to a skilled workforce.

Human papillomavirus testing 2007-2012: co-testing and triage utilization and impact on subsequent clinical management.

In the United States, high-risk human papillomavirus (HPV) testing is recommended for women with atypical squamous cells of unknown significance (ASC-US) cytology, and co-testing with cytology and HPV is a recommended option for screening women aged ≥ 30 years. No population-based data are available to examine utilization of HPV testing in the United States. Using the New Mexico HPV Pap Registry data resource, we describe population trends (2007-2012) in utilization and positivity rates for HPV testing as a routine co-testing screening procedure and for triage of ASC-US and other cytologic outcomes. For women aged 30-65 years co-testing increased from 5.2% in 2007 to 19.1% in 2012 (p < 0.001). Overall 82% of women with ASC-US cytology who did not receive co-testing also had an HPV test. HPV positivity was age and cytology result dependent but did not show time trends. For women with negative cytology, 64% received an additional screening test within 3 years if no co-test was done or if it was positive, but this was reduced to 47% with a negative co-test. Reflex HPV testing for ASC-US cytology is well established and occurs in most women. Evidence for reflex testing is also observed following other abnormal cytology outcomes. Co-testing in women aged 30-65 years has more than tripled from 2007 to 2012, but was still only used in 19.1% of women aged 30-65 years attending for screening in 2012. Women receiving co-testing had longer repeat screening intervals, but rescreening within 3 years is still very common even with co-testing.

Histology Findings after Two Years of Cytology/HPV Co-Testing in Germany.

Introduction: Since 1 January 2020, diagnostic confirmation of abnormalities detected in the context of cytology/HPV co-testing in cervical cancer screening under the statutory health insurance scheme in women aged 35 and over has been performed according to predefined algorithms. A colposcopy is indicated even in the case of borderline/low-grade cytological changes and/or HPV persistence. In this article we compare the histology findings after primary screening examinations in 2020/21 with those from 2018/19, thus also comparing the results of two different screening approaches. Patients and Methods: Our analysis included all of the cytology, HPV, and histology results from all primary screening examinations, as well as the resulting diagnostic confirmation and curative cases, that could be obtained by 30 June 2023. In 2018/19 these comprised 650600 cytology and 1804 histology findings, and in 2020/21 there were 491450 cytology and 7156 histology findings. The absolute numbers of histology findings and the percentage ratios of these to all cytological diagnoses are presented with comparison factors. Results: In 2020/21 there were 5.2 times more histology findings in relation to all previous cytology examinations than in 2018/19, as well as 10.6 times more biopsies, 3.8 times more conizations, and 1.2 times more hysterectomies. There was a particularly high increase in diagnostic confirmation of borderline/low-grade or only HPV-positive findings. With co-testing, 12.7 times more CIN1, 6.4 times more CIN2, and 3.5 times more CIN3 lesions were diagnosed. The proportion of biopsies without dysplasia was 7.6 times higher than in previous years. Cervical carcinomas were diagnosed 1.8 times more frequently, and endometrial carcinomas 0.7 times less frequently. Conclusion: More CIN lesions were found with co-testing, but the increase in histology findings of low-grade or no dysplasia was far greater than findings of CIN3. Lesions not requiring treatment accounted for 94.4% of biopsy results in 2020/21. The use of computer-assisted LBC with progression markers could reduce this.

Cervical Cancer Screening.

Cervical cancer screening is an essential component of preventative health care. Although rates of cervical cancer have decreased over the last 50 years, survival has not changed dramatically, and there are significant discrepancies in disease detection by race. Multiple national organizations contribute to the recommendations for cervical cancer screening timing, testing modalities, and management. This article aims to summarize the current understanding of cervical cancer pathogenesis, options for cervical cancer screening, and the shift in guidelines toward risk-based clinical management.

Emergency Department Co-testing for Human Immunodeficiency Virus When Testing for Gonorrhea and Chlamydia: A Readily Available, Missed Opportunity for Targeted HIV Testing in Emergency Departments.

OBJECTIVES: Conducting human immunodeficiency virus (HIV) testing in emergency departments (EDs) can be an effective approach to testing and reaching populations at highest risk of contracting HIV. METHODS: All gonorrhea and chlamydia (G/C) and HIV tests ordered in the Cleveland Clinic Health System's 14 EDs were included in the analysis. Data were collected from electronic health records. Descriptive statistics, with medians and means, were computed. RESULTS: From January 1, 2019, to December 31, 2021, we reviewed ED visits for the purpose of sexually transmitted infection (STI) screening, with an emphasis on G/C screening. In October 2019, both HIV rapid testing and G/C testing began across all 14 Cleveland Clinic EDs. The overall rate of co-testing for HIV when obtaining a G/C test for STI evaluation increased overall to around 30% for our health system EDs, with some individual EDs approaching 60%. CONCLUSIONS: The approach the Cleveland Clinic implemented is an effective way to test for HIV in the ED. Local health departments and stakeholders in HIV communities should support and collaborate with EDs in their jurisdictions to accelerate HIV testing initiatives by using an HIV plus G/C co-testing metric.