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Neither one-time negative screening tests nor negative colposcopy provides absolute reassurance against cervical cancer.

ABSTRACT: A population sample of 10,049 women living in Guanacaste, Costa Rica, was recruited into a natural history of human papillomavirus (HPV) and cervical neoplasia study in 1993-1994. At the enrollment visit, we applied multiple state-of-the-art cervical cancer screening methods to detect prevalent cervical cancer and to prevent subsequent cervical cancers by the timely detection and treatment of precancerous lesions. Women were screened at enrollment with 3 kinds of cytology (often reviewed by more than one pathologist), visual inspection and cervicography. Any positive screening test led to colposcopic referral and biopsy and/or excisional treatment of CIN2 or worse. We retrospectively tested stored specimens with an early HPV test (hybrid capture tube test) and for >40 HPV genotypes using a research PCR assay. We followed women typically 5-7 years and some up to 11 years. Nonetheless, 16 cases of invasive cervical cancer were diagnosed during follow-up. Six cancer cases were failures at enrollment to detect abnormalities by cytology screening; 3 of the 6 were also negative at enrollment by sensitive HPV DNA testing. Seven cancers represent failures of colposcopy to diagnose cancer or a precancerous lesion in screen-positive women. Finally, 3 cases arose despite attempted excisional treatment of precancerous lesions. Based on this evidence, we suggest that no current secondary cervical cancer prevention technologies applied once in a previously under-screened population is likely to be 100% efficacious in preventing incident diagnoses of invasive cervical cancer.

SUBMITTER: Castle PE

PROVIDER: S-EPMC2766540 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Neither one-time negative screening tests nor negative colposcopy provides absolute reassurance against cervical cancer.

Castle Philip E PE Rodríguez Ana C AC Burk Robert D RD Herrero Rolando R Hildesheim Allan A Solomon Diane D Sherman Mark E ME Jeronimo Jose J Alfaro Mario M Morales Jorge J Guillén Diego D Hutchinson Martha L ML Wacholder Sholom S Schiffman Mark M

International journal of cancer 20091001 7

A population sample of 10,049 women living in Guanacaste, Costa Rica, was recruited into a natural history of human papillomavirus (HPV) and cervical neoplasia study in 1993-1994. At the enrollment visit, we applied multiple state-of-the-art cervical cancer screening methods to detect prevalent cervical cancer and to prevent subsequent cervical cancers by the timely detection and treatment of precancerous lesions. Women were screened at enrollment with 3 kinds of cytology (often reviewed by more ...[more]

PMID: 19569231

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Project description:BACKGROUND:The World Health Organization (WHO) called for global action towards the elimination of cervical cancer. One of the main strategies is to screen 70% of women at the age between 35 and 45?years and 90% of women managed appropriately by 2030. So far, approximately 85% of cervical cancers occur in low- and middle-income countries (LMICs). The colposcopy-guided biopsy is crucial for detecting cervical intraepithelial neoplasia (CIN) and becomes the main bottleneck limiting screening performance. Unprecedented advances in artificial intelligence (AI) enable the synergy of deep learning and digital colposcopy, which offers opportunities for automatic image-based diagnosis. To this end, we discuss the main challenges of traditional colposcopy and the solutions applying AI-guided digital colposcopy as an auxiliary diagnostic tool in low- and middle- income countries (LMICs). MAIN BODY:Existing challenges for the application of colposcopy in LMICs include strong dependence on the subjective experience of operators, substantial inter- and intra-operator variabilities, shortage of experienced colposcopists, consummate colposcopy training courses, and uniform diagnostic standard and strict quality control that are hard to be followed by colposcopists with limited diagnostic ability, resulting in discrepant reporting and documentation of colposcopy impressions. Organized colposcopy training courses should be viewed as an effective way to enhance the diagnostic ability of colposcopists, but implementing these courses in practice may not always be feasible to improve the overall diagnostic performance in a short period of time. Fortunately, AI has the potential to address colposcopic bottleneck, which could assist colposcopists in colposcopy imaging judgment, detection of underlying CINs, and guidance of biopsy sites. The automated workflow of colposcopy examination could create a novel cervical cancer screening model, reduce potentially false negatives and false positives, and improve the accuracy of colposcopy diagnosis and cervical biopsy. CONCLUSION:We believe that a practical and accurate AI-guided digital colposcopy has the potential to strengthen the diagnostic ability in guiding cervical biopsy, thereby improves cervical cancer screening performance in LMICs and accelerates the process of global cervical cancer elimination eventually.

Project description:ObjectivesLogistical and economic issues make traditional cytology-based cervical cancer screening challenging in developing countries. Alternative, cost-effective, screening strategies must be developed to screen millions of women in resource-poor countries such as Cambodia.DesignA prospective cohort study during which all women underwent four cervical cancer screening methods: (1) self-sampled human papilloma virus (HPV) testing (careHPV system), (2) clinician-collected HPV testing, (3) visualization with acetic acid (VIA) and (4) digital colposcopy (DC) with the Enhanced Visual Assessment System (EVA).SettingA referral hospital in Phnom Penh, Cambodia.ParticipantsTwo hundred and fifty Cambodian women (129 HIV+, 121 HIV-). Subjects were recruited from the National Center for HIV/AIDS Dermatology and sexually transmitted disease (STD) cohort, the Sihanouk Hospital Center of Hope's Rural Outreach Teams and the Pochentong Medical Center.ResultsFifty six of the 250 (22.4%) patients tested positive for high-risk HPV (hrHPV+). Thirty seven of the 129 HIV+ women were hrHPV+ (28.6%) whereas 19/121 HIV- women were hrHPV+ (15.7%) p=0.0154. Self-sampling HPV specimens identified 50/56 (89%) whereas physician-collected specimens identified 45/56 (80%) p=0.174. 95.2% of the patients felt comfortable obtaining HPV self-samples. Thirty seven of 250 women were VIA+. Thirty of 37 VIA+ women underwent confirmatory biopsies for cervical intraepithelial neoplasia (CIN) (26 CIN1, 4 CIN2+). The rate of confirmed dysplasia in the HIV+ group was 20/129 (15.5%) compared with 10/121 (8.26%) in HIV- women p=0.0291. The contemporaneous physician impressions of the DC images accurately differentiated between CIN1 and CIN2+ lesions in all 30 women having confirmatory biopsies.ConclusionsThe results of this study suggest potential modifications of the current cervical screening strategy that is currently being employed in Cambodia. The first step in this new strategy would be self-swabbing for hrHPV. Subsequently, hrHPV+ patients would have DC and immediate treatment based on colposcopic findings: cryotherapy for suspected CIN1 and loop electrosurgical excision procedure (LEEP) for suspected CIN2+.

Project description:OBJECTIVE:To evaluate the performance of routine endocervical curettage (ECC) for diagnosing high-grade cervical intraepithelial neoplasia (CIN) 2 or worse and additional precancers not otherwise detected by ectocervical biopsies. METHODS:In a secondary analysis of the Biopsy Study, a cross-sectional study conducted between 2009 and 2012 at the University of Oklahoma Health and Sciences Center that found an incremental increase in detection of cervical precancers by multiple biopsies at colposcopy, ECC was performed in most women aged 30 years or older. Cervical intraepithelial neoplasia 2 or worse yield by ECC alone was evaluated in analyses stratified by cervical cytology (atypical squamous cells of undetermined significance [ASC-US] or low-grade squamous intraepithelial lesions [LSIL] compared with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions [ASC-H] or high-grade squamous intraepithelial lesions [HSIL] or worse), colposcopic impression (less than high-grade compared with high-grade), human papillomavirus (HPV)-16 infection status, whether the examination was satisfactory, and by ECC indications per the current guidelines for cervical cancer screening. The diagnostic value of ECC for detecting additional disease was evaluated by the number of lesion-directed ectocervical biopsies. RESULTS:Of the 204 women aged 30 years or older, 181 (88.7%) underwent ECC. Overall ECC detected 14.4% CIN 2 or worse (95% CI 10.0-20.2%). Endocervical curettage was more likely to find disease in the endocervix among women with high-grade cytology, positive HPV-16 infection, or high-grade colposcopic impressions (respective P values <.05). Among women with ASC-US or LSIL cytology, those with an unsatisfactory examination had a 13.0% CIN 2 or worse yield on ECC (95% CI 6.1-25.7); when colposcopic examination was normal or satisfactory with visible abnormal lesions, ECC detected less than 5% CIN 2 or worse in the endocervix. An ASC-H or HSIL or worse cytology was associated with a CIN 2 or worse yield of 25.8% by ECC (95% CI 16.6-37.9%). However, ECC found only 3.9% (95% CI 1.9-7.8%) additional CIN 2 or worse beyond the cumulative disease detected by up to four biopsies of visible acetowhite ectocervical lesions. Additional CIN 2 or worse yield by ECC increased when fewer lesion-directed biopsies were taken (P<.05). CONCLUSION:The additional yield of CIN 2 or worse by ECC in a colposcopy with up to four ectocervical biopsies was low. Based on our findings, we recommend routine ECC be performed in women aged 45 years old or older with HPV-16 infection and in any woman aged 30 years or older with HSIL or worse or ASC-H cytology, high-grade colposcopic impression, or ASC-US or LSIL cytology and an unsatisfactory examination. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT00339989.

Project description:BACKGROUND:Cervical-vaginal fluid (CVF) plays an important role in the prevention of gynecological infections, although little is known about the contribution of CVF proteins to the immunity of the lower female genital tract. In order to analyze the protein composition of human CVF, we used CVF samples that are routinely collected during colposcopy, but are usually discarded. Since these samples are available in large quantities we aimed to analyze their usefulness for proteomics experiments. The samples were analyzed using different prefractionation techniques (ultrafiltration and C4(RP)-LC protein separation) followed by C18(RP)-LC peptide separation and identification by MALDI-TOF-TOF mass spectrometry. To determine the reproducibility of this proteomics platform we analyzed three technical replicates. Using spectral counting, protein abundances were estimated in a semiquantitative way. We also compared the results obtained in this study with those from previous studies derived from patients with different physiological conditions in order to determine an overlapping protein set. RESULTS:In total, we were able to identify 339 proteins in human CVF of which 151 proteins were not identified in any other proteomics study on human CVF so far. Those included antimicrobial peptides, such as human beta-defensin 2 and cathelicidin, which were known to be present in CVF, and endometrial proteins such as glycodelin and ribonucleoprotein A. Comparison of our results with previously published data led to the identification of a common protein set of 136 proteins. This overlapping protein set shows increased fractions of immunological and extracellular proteins, confirming the extracellular immunological role of CVF. CONCLUSION:We demonstrated here that CVF colposcopy samples can be used in proteomics experiments and hence are applicable for biomarker discovery experiments. The delineation of an overlapping set of proteins that is identified in most proteomics studies on CVF may help in the description of a reference proteome when performing proteomics studies on human CVF.

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Neither one-time negative screening tests nor negative colposcopy provides absolute reassurance against cervical cancer.

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Neither one-time negative screening tests nor negative colposcopy provides absolute reassurance against cervical cancer.

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