High-risk Human Papillomavirus Test Results Research Articles

Prevalence of high-risk HPV and cervical dysplasia in IUD users and controls: a cross sectional study

Objective To examine the prevalence of infections with high-risk human papillomavirus (HPV) and cervical dysplasia, and the clearance rate of HPV infections, in users of different kinds of intrauterine devices (IUDs) and other contraceptive methods. Methods A cross-sectional register-based study including 16,181 women aged 30–49 years participating in the screening programme for cervical cancer in a Swedish County in 2017–2018. Data on contraception from screening records was paired with the HPV test results, cytological and histological follow-up tests and subsequent HPV test. Results There was no difference in the risk of being HPV positive, or histological HSIL+, between users of copper-containing IUDs and women with no reported use of contraception. Use of levonorgestrel intrauterine system and hormonal contraception were associated with higher odds for HPV infection in age-adjusted models (aOR 1.21; 95% CI 1.04–1.41, and aOR 1.41; 95% CI 1.22–1.63, respectively) and for HSIL+ (aOR 1.45; 95% CI 1.02–2.06, and aOR 1.56; 95% CI 1.13–2.16, respectively). No significant differences were found in HPV clearance rates. Conclusions Reported use of levonorgestrel intrauterine system and hormonal contraception, but not use of copper IUD, was associated with a higher prevalence of HPV infections and histological HSIL + compared to no reported use of contraception.

Abstract 2142: Spatial distribution of high-risk human papillomavirus (HR-HPV) across 23 Chicago community areas and correlates

Abstract Background: Despite availability of effective vaccines and screening, cervical cancer claimed 4,280 lives in 2022. We explored the spatial distribution of high-risk human papillomavirus (“HR-HPV”) infection across 23 Chicago Community Areas (CCAs) served by the University of Illinois Health Network (UI Health). Using a modified Warnecke et al Health Disparity Outcomes (HDO) model, we hypothesized that CCAs with higher rates of structural violence, the social, economic, and political systems exposing populations to risks and vulnerabilities, would correlate with increased HR-HPV. Methods: Electronic medical records of patients receiving routine cervical cancer screening between January 1, 2015 and December 31, 2019 were reviewed. As per the 2014 ACS guidelines. HR-HPV test results were captured as HR-HPV positive, HR-HPV-16, HR-HPV-18 and non-16/18 HR-HPV, the latter consisting of 12 HR-HPV subtypes. Structural violence variables were used from Chicago Health Atlas (2015-2019) with percent poverty, hardship index score, easy access to fruit and vegetables, routine checkup, homicide, and primary care provider across CCAS. Univariate Poisson regression was used to compare the associations between selected structural violence factors and HR-HPV prevalence. Univariate multinomial logistic regression evaluated associations between structural violence indicators and HR-HPV subtypes Global p-values were obtained using ANOVA at 0.05 significance. Results: 8,566 women met inclusion criteria out of 13,466 total women. 75% were Black or Hispanic. Overall prevalence of cervical HR-HPV infection was 20.3% (n=1,737), ranging from 8.7% to 27.2% across CCAs. Median age for women was 36. Percent with primary care provider was negatively associated with HPV infection (IRR = 0.99 with 95% CI (0.98, 1.00), adjusted p-value=0.023), indicating women living in CCAs with higher rates of primary care provider were less likely to have HR-HPV. Easy access to fruit and vegetables (adjusted p-value = 0.007) and percent with primary care provider (adjusted p-value = 0.009) were significantly associated with HR-HPV subtypes. Women living in CCAs with easy access to fruit and vegetables (OR = 0.99, with 95% CI (0.98,0.99)) as well as those with higher rates of primary care provider (OR = 0.98, with 95% CI (0.97,0.99)) were less likely to have non-16/18 HR-HPV. Conclusion: HR-HPV is the most common sexually transmitted infection, and most women clear the infection naturally. As the origin of 99% of cervical cancer, understanding the reasons HR-HPV persists and progresses to cancer among certain individuals and groups is critical. Novel interventions like increasing access to fruit and vegetables could compliment widely available and effective vaccines. Citation Format: Gelila Goba, Jiehuan Sun, Quetzal Class, Joel Schwartz, Sage Kim, Karriem Watson, Lisa Tussing-Hummphreys, Yamile Molina, Shannon MacLaughlan, Ziqiao Xu, Benjamin Aldred, Subhash Kumar Kolar Rajanna, Tamika Alexander, Anna-Barbara Moscicki. Spatial distribution of high-risk human papillomavirus (HR-HPV) across 23 Chicago community areas and correlates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2142.

High-Risk Human Papillomavirus Test Results in Unsatisfactory Cytology Specimens Compared to Satisfactory Cytology Specimens

High-Risk Human Papillomavirus Test Results in Unsatisfactory Cytology Specimens Compared to Satisfactory Cytology Specimens

Histopathologic Follow-Up of Women with Inadequate ThinPrep™ Cervical Pap Tests and Positive High-Risk Human Papillomavirus Test Results

Introduction: We found only a few studies that had performed high-risk human papillomavirus (hrHPV) analyses of inadequate ThinPrep™ Papanicolaou (Pap) tests. Therefore, this study aimed to analyze unsatisfactory ThinPrep Pap tests using hrHPV tests. The colposcopic biopsy results of cases with an unsatisfactory ThinPrep Pap test and positive hrHPV results were revealed. Methods: Between January 1, 2018, and October 31, 2022, 965 (3.7%) of 25,958 liquid-based cytology specimens were evaluated as unsatisfactory. Ninety-five (9.8%) of 965 patients were positive for hrHPV. The colposcopic evaluation was performed in 28 (29.4%) of 95 patients, in whom 23 tests were adequate. Results: Twenty-three colposcopy biopsy results showed that 17 (73.9%) of 23 patients had benign biopsy results. High-grade squamous intraepithelial lesions were observed in three (13%) of the 23 patients, and low-grade squamous intraepithelial lesions were observed in two (8.6%) of the 23 patients. One of the 23 (4.3%) patients had keratinized squamous cell carcinoma of the cervix diagnosed histologically, although no tumor was visible upon gynecologic examination. Conclusion: For the management of unsatisfactory Pap tests, The American Society for Colposcopy and Cervical Pathology (ASCCP) recommends repeat cytology within 2–4 months. Evaluation of such patients using hrHPV tests may triage those with squamous intraepithelial lesions, even invasive cervical cancer. More studies with a larger number of cases are needed to analyze the hrHPV status and biopsy follow-up of cases with unsatisfactory cytology.

Cytology interpretation after a change to HPV testing in primary cervical screening: Observational study from the English pilot.

BACKGROUNDOvercalling of abnormalities has been a concern for using cytology triage after positive high‐risk human papillomavirus (HPV) tests in cervical screening.METHODSThe authors studied the detection of cytological and histological abnormalities at age 24 to 64 years, using data from the English HPV pilot. The pilot compared routine implementation of primary cervical screening based on cytology (N = 931,539), where HPV test results were not available before cytology reporting, with that based on HPV testing (N = 403,269), where cytology was only required after positive HPV tests.RESULTSRevealed HPV positivity was associated with a higher direct referral to colposcopy after any abnormality (adjusted odds ratio [ORadj], 1.16; 95% confidence interval [CI], 1.14‐1.18). Laboratories with higher direct referral referred fewer persistently HPV‐positive women after early recall. The detection of high‐grade cervical intraepithelial neoplasia (CIN2+) after direct referral increased with an ORadj of 1.17 (95% CI, 1.13‐1.20) for informed versus uninformed cytology. Generally, the positive predictive value (PPV) of colposcopy for CIN2+ remained comparable under both conditions of interpreting cytology. In women 50 to 64 years old with high‐grade dyskaryosis, however, the PPV increased from 71% to 83% after revealing HPV positivity (ORadj, 2.05; 95% CI, 1.43‐2.93).CONCLUSIONSQuality‐controlled cervical screening programs can avoid inappropriate overgrading of HPV‐positive cytology.;

Rescreening Practices of Negative Papanicolaou Tests With Positive Human Papillomavirus Test Result.

The yield of the prospective rescreening process for "negative for intraepithelial lesion or malignancy" (NILM) Papanicolaou (Pap) tests is higher with the inclusion of a greater proportion of high-risk cases. One of the suggested criteria for classifying a Pap test finding as high risk is recent or concurrent high-risk human papillomavirus (HPV) positivity. To evaluate how the results of HPV testing have been incorporated in the prospective rescreening of NILM Pap tests across a wide range of laboratories. A questionnaire survey was sent to laboratories participating in the 2019 College of American Pathologists (CAP) Gynecologic Cytology (PAP Education) Program. Of the 1507 participating laboratories, 667 (44%) responded to the survey. Most laboratories (59.4%; 396 of 667) had not incorporated HPV test/genotyping results to select NILM Pap tests for rescreening. Amongst the remaining laboratories, for NILM HPV-positive Pap test results, 112 (16.8%) had a policy to rescreen by a cytotechnologist only, 51 (7.6%) by a pathologist only, and 86 (12.9%) by both. Of 264 laboratories, 181 (68.6%) reported the cytology upon availability of the HPV test result and completion of the secondary review. Of 661 laboratories, 145 (21.9%) included consensus-type recommendations in the cytology report for such Pap tests. This CAP survey provides significant information regarding the current trends in the use of HPV test results in prospective rescreening of NILM Pap tests. Future studies on quality improvement can further assist in the standardization of this process across different laboratories.

Comparison of papanicolaou smear and human papillomavirus (HPV) test as cervical screening tools: can we rely on HPV test alone as a screening method? An 11-year retrospective experience at a single institution.

BackgroundThe decrease in incidence of cervical dysplasia and carcinoma has not been as dramatic as expected with the development of improved research tools and test methods. The human papillomavirus (HPV) test alone has been suggested for screening in some countries. The National Cancer Screening Project in Korea has applied Papanicolaou smears (Pap smears) as the screening method for cervical dysplasia and carcinoma. We evaluated the value of Pap smear and HPV testing as diagnostic screening tools in a single institution.MethodsPatients co-tested with HPV test and Pap smear simultaneously or within one month of each other were included in this study. Patients with only punch biopsy results were excluded because of sampling errors. A total of 999 cases were included, and the collected reports encompassed results of smear cytology, HPV subtypes, and histologic examinations.ResultsSensitivity and specificity of detecting high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) were higher for Pap smears than for HPV tests (sensitivity, 97.14%; specificity, 85.58% for Pap smears; sensitivity, 88.32%; specificity, 54.92% for HPV tests). HPV tests and Pap smears did not differ greatly in detection of low-grade squamous intraepithelial lesion (85.35% for HPV test, 80.31% for Pap smears). When atypical glandular cells were noted on Pap smears, the likelihood for histologic diagnosis of adenocarcinoma following Pap smear was higher than that of high-risk HPV test results (18.8 and 1.53, respectively).ConclusionsPap smears were more useful than HPV tests in the diagnosis of HSIL, SCC, and glandular lesions.

Atypical Squamous Cells in Liquid-Based Cervical Cytology: Microbiology, Inflammatory Infiltrate, and Human Papillomavirus-DNA Testing

Objective: The aim of this study was to assess the correlation between atypical squamous cells (ASC) and inflammatory infiltrate and vaginal microbiota using cervical liquid-based cytological (SurePath®) and high-risk human papillomavirus (HR-HPV) tests. Study Design: A cross-sectional study was conducted using a 6-year database from a laboratory in Fortaleza (Brazil). Files from 1,346 ASC cases were divided into subgroups and results concerning inflammation and vaginal microorganisms diagnosed by cytology were compared with HR-HPV test results. Results: An absence of specific microorganisms (ASM) was the most frequent finding (ASC of undetermined significance, ASC-US = 74%; ASC - cannot exclude high-grade squamous intraepithelial lesion, ASC-H = 68%), followed by bacterial vaginosis (ASC-US = 20%; ASC- H = 25%) and Candida spp. (ASC-US = 6%; ASC-H = 5%). Leukocyte infiltrate was present in 71% of ASC-US and 85% of ASC-H (p = 0.0040), and in these specific cases HR-HPV tests were positive for 65 and 64%, respectively. A positive HR-HPV test was relatively more frequent when a specific microorganism was present, and Candida spp. was associated with HR-HPV-positive results (p = 0.0156), while an ASM was associated with negative HR-HPV results (p = 0.0370). Conclusion: ASC-US is associated with an absence of inflammation or vaginosis, while ASC-H smears are associated with Trichomonas vaginalis and inflammatory infiltrate. A positive HR-HPV is associated with Candida spp. in ASC cytology.

Cross-reactivity profiles of hybrid capture II, cobas, and APTIMA human papillomavirus assays: split-sample study.

BackgroundHigh-risk Human Papillomavirus (HPV) testing is replacing cytology in cervical cancer screening as it is more sensitive for preinvasive cervical lesions. However, the bottleneck of HPV testing is the many false positive test results (positive tests without cervical lesions). Here, we evaluated to what extent these can be explained by cross-reactivity, i.e. positive test results without evidence of high-risk HPV genotypes. The patterns of cross-reactivity have been thoroughly studied for hybrid capture II (HC2) but not yet for newer HPV assays although the manufacturers claimed no or limited frequency of cross-reactivity. In this independent study we evaluated the frequency of cross-reactivity for HC2, cobas, and APTIMA assays.MethodsConsecutive routine cervical screening samples from 5022 Danish women, including 2859 from women attending primary screening, were tested with the three evaluated DNA and mRNA HPV assays. Genotyping was undertaken using CLART HPV2 assay, individually detecting 35 genotypes. The presence or absence of cervical lesions was determined with histological examinations; women with abnormal cytology were managed as per routine recommendations; those with normal cytology and positive high-risk HPV test results were invited for repeated testing in 18 months.ResultsCross-reactivity to low-risk genotypes was detected in 109 (2.2 %) out of 5022 samples on HC2, 62 (1.2 %) on cobas, and 35 (0.7 %) on APTIMA with only 10 of the samples cross-reacting on all 3 assays. None of the 35 genotypes was detected in 49 (1.0 %), 162 (3.2 %), and 56 (1.1 %) samples, respectively. In primary screening at age 30 to 65 years (n = 2859), samples of 72 (25 %) out of 289 with high-risk infections on HC2 and < CIN2 histology were due to cross-reactivity. On cobas, this was 106 (26 %) out of 415, and on APTIMA 48 (21 %) out of 224.ConclusionsDespite manufacturer claims, all three assays showed cross-reactivity. In primary cervical screening at age ≥30 years, cross-reactivity accounted for about one quarter of false positive test results regardless of the assay. Cross-reactivity should be addressed in EU tenders, as this primarily technical shortcoming imposes additional costs on the screening programmes.

Immediate risk of HSIL presence in women who have both ASC-US cytology and negative high-risk HPV test.

The authors aimed to detect immediate risk of having high grade squamous lesions (HSIL) in atypical squamous cells of uncertain significance(AS-CUS) and concomitant high-risk human papillomavirus (HrHPV) testing as negative [HrHPV(negative)AS-CUS]. The authors performed immediate/baseline colposcopy on concomitant HrHPV (negative)AS-CUS cases. Pap tests were evaluated with liquid-based cytology (LBC) and HrHPV detection was performed in LBC material with PCR. Colposcopic diagnoses and biopsy results were compared with Pap test and HrHPV test results. There were 104 patients over a one-year period. In all, 84 cases were included. Colposcopic biopsies revealed low grade squamous intraepithelial lesion (LSIL) in 19 cases (23%) and HSIL in three cases (4%). Intrauterine device use and smoking were significantly correlated with presence of HSIL (p = 0.005 and p = 0.007 respectively). Similar data in literature, 4% of ASC-US-HrHPV (negative) cases are expected to have HSIL in follow-up periods less than six months. The present authors believe clinicians should be more open with their patients about limitations of Pap-HPV testing.

Prevalence of High-Risk Human Papillomavirus Infection in China: Analysis of 671,163 Human Papillomavirus Test Results From China's Largest College of American Pathologists-Certified Laboratory.

This study on human papillomavirus (HPV) testing in China's largest independent laboratory accredited by the international Laboratory Accreditation Program of the College of American Pathologists extends previous reports on cervical screening test results from this Chinese facility. A retrospective laboratory database search from 2007 to 2014 documented high-risk HPV test results using either Hybrid Capture 2 (HC2; Qiagen, Hilden, Germany) or multiplex polymerase chain reaction fluorescence testing (MPFT) methods. During the study period, HPV testing steadily increased, with 643,702 HC2 and 27,641 MPFT HPV tests performed. The mean ages of the tested women were 35.0 years using HC2 and 38.3 years using MPFT. The HC2 HPV-positive rate was 21.7%, significantly higher than 15.7% with MPFT (P < .0001), with bimodal peak incidence in adolescents and women aged 60 to 69 years. Use of HPV testing in cervical screening is increasing in China. HC2 HPV-positive rates around 20% in all age groups from more than 500,000 tested Chinese women are consistent with previous reports from China and significantly higher than published HC2 HPV-positive rates in populations with more widespread cervical screening. MPFT HPV-positive rates were slightly lower in every age group. The high HPV-positive rate likely reflects limited routine cervical screening and high cervical cancer incidence in China.

Associations between sexually transmitted infections, high-risk human papillomavirus infection, and abnormal cervical Pap smear results in OB/GYN outpatients.

ObjectiveThis study aimed to examine the meaning and usefulness of sexually transmitted infection (STI) test when caring for patients who have abnormal cervical cytology and/or positive high-risk human papillomavirus (HPV) DNA test results.MethodsAmong patients who underwent liquid-based cervical cytology and HPV DNA tests at the Obstetrics and Gynecology outpatient clinic, 800 patients who showed abnormal cervical cytology were compared with 200 patients in the control group. Both groups were simultaneously tested via multiplex real-time polymerase chain reaction for seven types of STI-causative microorganisms.ResultsThe positive rate of high-risk HPV infection in total STIs positive group was 1.47 times higher than that of total STIs negative group. The probability of a cytological diagnosis of a grade equal to or higher than atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H) was significantly higher in patients testing positive for total STIs (1.46 times), Chlamydia trachomatis (3.21 times), or Mycoplasma genitalicum (3.58 times) than in those testing negative. The total STIs positive rate was significantly higher for those having a cytological diagnosis of a grade equal to or higher than atypical squamous cells of undetermined significance (ASC-US) when high-risk HPV test result was negative.ConclusionCorrelations were present not only between STIs and high-risk HPV infection but also between abnormal cervical cytology and STIs. Therefore, additional evaluation of STIs will be helpful to appropriately diagnose and treat patients with abnormal cervical cytology, positive results on high-risk HPV DNA test, or a cytological diagnosis of ASC-US despite negative high-risk HPV DNA test result.

The American Society for Colposcopy and Cervical Pathology Guidelines for Unsatisfactory Pap Smears with High-Risk Human Papillomavirus Co-testing: A Quality Assurance Review

The recommendation for unsatisfactory Pap smears endorsed by the new American Society for Colposcopy and Cervical Pathology (ASCCP) 2013 guidelines is based on the high-risk human papillomavirus (HPV) DNA (hr-HPV) testing status. For women with unsatisfactory cytology with either an unknown or a negative HPV test result, repeat cytology in 2 to 4 months is recommended. …

Prevalence of HPV 16/18 genotypes and histopathologic follow-up outcomes in women with negative cytology and positive high-risk HPV test results

Management of human papillomavirus (HPV)-positive/cytology-negative patients has represented a special challenge ever since the introduction in 2003 of routine cytology and HPV cotesting of women 30 years and older. Since the U.S. Food and Drug Administration's approval in 2009 of an HPV 16/18 genotyping test, guidelines have included an HPV 16/18 genotyping triage option for identifying high-risk HPV-positive/cytology-negative patients who would benefit from immediate colposcopic referral. A retrospective database search was conducted to identify patients with HPV-positive/cytology-negative results between May 1, 2010 and June 30, 2013 in an academic women's hospital practice in which clinical staff consented to routine HPV 16/18 genotyping triage testing of women 30 years and older with HPV-positive/cytology-negative results. Of 824 cytology-negative/HPV-positive cases with valid HPV 16/18 genotyping results, positive results were obtained in 101 (12.3%). HPV 16 was detected most frequently (9.1%), followed by HPV 18(2.4%) and both 16 and 18 (0.7%). Histopathologic follow-up results were documented over an average of 3.5 months (range 0.5 to 22.5) in 51 patients with HPV-positive/cytology-negative/HPV 16/18-positive results; cervical intraepithelial neoplasia 2/3 biopsy diagnoses were reported in 4 of 51 (7.8%). Previously we reported cervical intraepithelial neoplasia 2+ diagnoses in 2.4% of 849 high-risk HPV-positive/cytology-negative patients followed for almost 2 years without HPV 16/18 genotype testing. These initial routine clinical practice findings are consistent with data from both long-term research studies and recent shorter term clinical trials indicating enhanced risk stratification of HPV-positive/cytology negative patients with HPV 16/18 genotype testing. This is the first report of the application of this option in a routine clinical practice setting.

Vaginal self-sampling is a cost-effective way to increase participation in a cervical cancer screening programme: a randomised trial.

Background:Cervical cancer screening coverage remains insufficient in most countries. Our objective was to assess whether in-home vaginal self-sampling with a dry swab for high-risk human papillomavirus (HR-HPV) testing is effective and cost-effective in increasing participation in cervical cancer screening.Methods:In March 2012, 6000 unscreened women aged 30–65 years, living in a French region covered by a screening programme, who had not responded to an initial invitation to have a Pap smear were equally randomised to three groups: ‘no intervention' ‘recall', women received a letter to have a Pap smear; and ‘self-sampling', women received a self-sampling kit to return to a centralised virology laboratory for PCR-based HPV testing.Results:Participation was higher in the ‘self-sampling' than in the ‘no intervention' group (22.5% vs 9.9%, P<0.0001; OR 2.64) and ‘recall' group (11.7%, P<0.0001; OR 2.20). In the ‘self-sampling' group, 320 used the self-sampling kit; for 44 of these women with positive HR-HPV test results, 40 had the recommended triage Pap smear. The ICER per extra screened woman was 77.8€ and 63.2€ for the ‘recall' and ‘self-sampling' groups, respectively, relative to the ‘no intervention' group.Conclusions:Offering an in-home, return-mail kit for vaginal self-sampling with a dry swab is more effective and cost-effective than a recall letter in increasing participation in cervical cancer screening.

Type-specific HPV and Pap test results among low-income, underserved women: providing insights into management strategies

The primary cervical cancer screening strategy for women over age 30 is high-risk human papillomavirus (HPV) testing combined with Papanicolaou (Pap) testing (cotesting) every 5 years. This combination strategy is a preventive service that is required by the Affordable Care Act to be covered with no cost-sharing by most health insurance plans. The cotesting recommendation was made based entirely on prospective data from an insured population that may have a lower proportion of women with HPV positive and Pap negative results (ie, discordant results). The discordant group represents a very difficult group to manage. If the frequency of discordant results among underserved women is higher, health care providers may perceive the cotesting strategy to be a less favorable screening strategy than traditional Pap testing every 3 years. The Centers for Disease Control and Prevention's Cervical Cancer Study was conducted at 15 clinics in 6 federally qualified health centers across Illinois. Providers at these clinics were given the option of cotesting for routine cervical cancer screening. Type-specific HPV detection was performed on residual extracts using linear array. Pap test results were abnormal in 6.0% and HPV was positive in 7.2% of the underserved women screened in this study (mean age, 45.1 years). HPV prevalence decreased with age, from 10.3% among 30- to 39-year-olds to 4.5% among 50- to 60-year-olds. About 5% of the women had a combination of a positive HPV test and normal Pap test results; HPV 16/18 was identified in 14% of discordant women. The rate of discordant results among underserved women was similar to those reported throughout the US in a variety of populations. Typing for HPV 16/18 appears to assist in the management in a small proportion of women with discordant results.

Yield and Mode of Diagnosis of Cervical Intraepithelial Neoplasia 3 or Cancer Among Women With Negative Cervical Cytology and Positive High-Risk Human Papillomavirus Test Results

In women with negative cervical cytology and positive high-risk human papillomavirus (HR-HPV) test results, we compared the risk of cervical intraepithelial neoplasia 3 (CIN 3) or cancer (CIN 3+) in women with previous abnormal cervical cytology, CIN, or HR-HPV with that in women without this history, and we determined their cumulative risk of CIN 3+. We reviewed colposcopies for negative cytology and positive HR-HPV test results from 2007 to 2009 (colposcopy was done for previous abnormal cytology, HR-HPV, or CIN or if negative cytology and positive HR-HPV test results for 20-35 months). Women with negative cytology and positive HR-HPV test results in 2007 were reviewed to determine their cumulative risk of CIN 3+. Of the 513 women with colposcopy for negative cytology and positive HR-HPV test results, 367 had previous abnormal cytology, CIN, or HR-HPV greater than 35 months ago and 146 had negative cytology and positive HR-HPV test results for 20 to 35 months. Risk of CIN 3+ for women with negative cytology and positive HR-HPV test results with previous abnormal cytology, HR-HPV, or CIN who did not have previous colposcopy was 11.9% (8/67); for similar women with previous colposcopy, it was 2.7% (8/300); and for women with positive HR-HPV test result for 20 to 35 months, it was 7.5% (11/146). In 2007 to 2009, risk of CIN 3+ for women with cytology of atypical squamous cells of undetermined significance (ASC-US) with positive HR-HPV test result was 3.9% (60/1,540). Of the 1,726 women with negative cytology and positive HR-HPV test result in 2007, 381 (22.1%) were lost to follow-up. Of the 1,345 women with median follow-up of 44 months, 602 (44.8%) had 1 or 2 subsequent negative cytology and negative HR-HPV test results and 180 had subsequent positive HR-HPV test result without biopsy. Of the 563 women with biopsy, there were 711 evaluations. Invasive cancer was found in 4 and CIN 3 in 54 (cumulative CIN 3+ of 4.3%, 58/1,345). Half (29/58) of the cumulative CIN 3+ was diagnosed after subsequent abnormal cytology and positive HR-HPV test result. If referral to colposcopy of women with cervical cytology of ASC-US and positive HR-HPV test result (CIN 3+, 3.9%) is justified, referral to colposcopy of women with negative cytology and positive HR-HPV test results is justified if they have previous abnormal cervical cytology, CIN, or HR-HPV greater than 35 months ago but have not had previous colposcopy (CIN 3+=11.9%) or are persistently HR-HPV positive for 20 to 35 months (CIN 3+, 7.5%). The risk of CIN 3+ in women with previous abnormal cytology, CIN, or HR-HPV who have previous colposcopy (2.7%) is lower because these women have incident rather than prevalent CIN 3+.

Clinical Performance Characteristics of the Cervista HPV HR Test Kit in Cervical Cancer Screening in China

A multicenter clinical trial was performed to evaluate and validate the performance of Cervista HPV HR test and to establish its effectiveness in identifying women at risk of having cervical intraepithelial neoplasia 2 (CIN 2) or higher grade (CIN 2+) in the Chinese population. Residual ThinPrep Pap Test samples from women who are negative for intraepithelial lesion or malignancy (NILM) and atypical squamous cells of undetermined significance (ASCUS) or higher grade cytology were tested for high-risk human papillomavirus (HPV). The HPV test results were compared with histology results to determine the clinical sensitivity, specificity, positive predictive value, and negative predictive value of Cervista HPV HR for CIN 2+. The analytical accuracy of Cervista HPV HR compared with consensus HPV L1 polymerase chain reaction (PCR)/sequencing was also determined. A total of 1,064 subjects were enrolled, including 544 with NILM cytology and 520 with ASCUS or higher grade cytology. Complete data sets including cytology, high-risk HPV test, colposcopy, and histology results for all subjects with ASCUS or higher grade were included in the analysis. The positive rate of Cervista HPV HR was 12.5% in patients with NILM and 69.04% in patients with ASCUS or higher grade. The overall percentage agreement between Cervista HPV HR and PCR with bidirectional sequencing was 86.26%, with positive percentage agreement and negative percentage agreement being 93.4% and 83.3%, respectively. In the overall population, the Cervista HPV HR positivity rate was 38.96% compared with 29.08% for PCR/sequencing. The clinical sensitivity and specificity for CIN 2+ of Cervista HPV HR were 98.50% and 68.21%, respectively. The negative and positive predictive values were 99.69% and 30.68%, respectively. The Cervista HPV HR test, performed on ThinPrep Pap Test samples, has the clinical performance characteristics required by China for use as part of routine cervical cancer screening.

Quantitative Analysis of Methylation Status of the PAX1 Gene for Detection of Cervical Cancer

Although aided by high-risk human papillomavirus (HPV) DNA test, early detection of cervical cancer is still a challenge. Hypermethylation of the paired boxed gene 1 (PAX1) was recently reported as a characteristic of cervical cancer. This study designed a quantitative measure of PAX1 methylation and compared its efficacy to the currently available Hybrid Capture 2 (HC2) HPV test in detection of cervical cancer. Using real-time quantitative methylation-specific polymerase chain reaction, we measured the percentage of PAX1 methylation in cervical scrapings obtained from a hospital-based cohort of women with cervical neoplasia of different severities and compared the efficacy of diagnosis of cervical cancer to that of the HC2 HPV test. From 73 cervical scrapings, with diagnoses of normal (n = 17), cervical intraepithelial neoplasm 1 (CIN1; n = 10), CIN2 (n = 18), CIN3 (n = 14), and invasive cancer (n = 14), the percentage of PAX1 methylation was determined. The percent of methylated reference of invasive cancer (mean [SE], 56.7 [7.1]) was significantly higher than CIN3 (6.5 [2.3]) and the other milder lesions (1.0 [0.3]; P < 0.0001). At a cutoff percent of methylated reference value of 4.5, PAX1 methylation was found in 100% of invasive cancer tissue as compared with 0% of normal tissue, 10% of CIN1, 11% of CIN2, and 43% of CIN3 (P < 0.0001). As a comparison, the HC2 HPV test result was positive in 5.9% of normal tissue, 70% of CIN1, 55.6% of CIN2, 71.4% of CIN3, and 100% of invasive cancer. In addition to cancer tissue, methylation of PAX1 was also found in normal tissue adjacent to the cancer lesion (9/11, 82%) but much less in the remote normal tissues (2/5, 40%), indicating a field methylation. In this hospital-based study, quantitative measurement of PAX1 hypermethylation in cervical scrapings is highly sensitive and is more specific than HC2 in detection of cervical cancer.

Diagnostic Efficacy of Real-Time Optical Coherence Tomography in the Management of Preinvasive and Invasive Neoplasia of the Uterine Cervix

Determine the sensitivity and specificity of optical coherence tomography (OCT) as an adjunct to colposcopy in the detection of cervical intraepithelial neoplasia (CIN) grade 2 or higher in a real-time clinical evaluation. Optical coherence tomography (OCT) uses infrared light similar to ultrasound pulse-echo imaging. Image resolution is optimal in the 1-to-3-mm range. This study is the third in our series of OCT investigations and our first real-time clinical trial. The study was conducted at the Peking University Shenzhen Hospital, Shenzhen, China. Nonpregnant women 18 years or older with abnormal cervical cytologic findings or a positive high-risk human papillomavirus test result were recruited. Women were assessed; and diagnoses, recorded by cervical quadrant first with colposcopy, followed by colposcopic directed OCT. A biopsy of the abnormal areas was performed. In normal quadrants, biopsy specimens were obtained at the 2-, 4-, 8-, and 10-o'clock positions at the squamocolumnar junction depending on the quadrant. An endocervical curettage was also done. Individual OCT diagnoses were paired with colposcopic impressions and biopsy specimens to assess its role as a paired secondary screen. Data were analyzed using generalized estimating equations to control for correlation within a woman. One thousand two hundred thirty-seven paired diagnoses from 299 women were analyzed. Median age was 36 years. Ninety-six women (8%) had a diagnosis of CIN 2 or higher. Evaluation by quadrant showed that the sensitivity for CIN 2 or higher decreased by adding OCT to colposcopy, but the specificity increased from 83% to 93%. We continue to try to improve sensitivity by improving the near-infrared light source, decreasing the scan time to 8 frames per second, and using a larger diameter (5 mm) fiberoptic probe with a newly designed application specific probe sheath.