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Biomedical subjects

Jose Jeronimo

Publications and source records attributed to Jose Jeronimo.

14 recordsLinked to original sources
PubMed2006

Description of patients with squamous cell carcinoma in the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion triage study.

BACKGROUND: The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS) accumulated information regarding conventional and liquid-based Papanicolaou (Pap) cytology, 2 kinds of human papillomavirus (HPV) DNA testing, cervicography, and colposcopically directed biopsy. The prevalence of squamous cell carcinoma in these women, the efficacy of tests, and the time to detection were reviewed. METHODS: The ALTS data base was reviewed for all women with invasive carcinoma. All results of colposcopy, HPV testing, cytology, biopsies, and cervigrams were reviewed for all women in the ALTS trial who were diagnosed with squamous cell carcinoma. RESULTS: There were 7 diagnoses of invasive cancer (all squamous cell) during the 2 years of the ALTS trial. Although the enrollment studies isolated many high-grade lesions, none of those results were diagnostic of the underlying carcinoma. CONCLUSIONS: The prevalence of squamous cell carcinoma in the setting of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion cytology interpretation appears to be low (approximately 1 per 1000 women in the ALTS trial). Many of the carcinomas were not visible on the ectocervix by cervicography or colposcopy, which may explain in part the paucity of atypical cells detected on the Pap tests and the finding that the presenting cytology, although abnormal, was never diagnostic of cancer. HPV DNA tests were positive in all 7 cancers. Type-specific testing identified HPV type 16 in 6 of 7 cancers and HPV type 18 in 1 of 7 cancers.

Adult↗
PubMed2006

Colposcopy at a crossroads.

New cervical cancer prevention strategies are arising from rapidly improving insight into human papillomavirus (HPV) natural history and cervical carcinogenesis, challenging the conventional roles of cytology and colposcopically directed biopsy as the reference standards of screening and diagnosis, respectively. HPV testing has high sensitivity but mediocre specificity and positive predictive value, making the role of colposcopy for the accurate identification of patients requiring treatment even more important. We believe that deficiencies of the colposcopically guided biopsy must be addressed, in particular, the inaccuracy of biopsy placement leading to low sensitivity for detection of CIN3. This opinion outlines our concerns and summarizes new data, suggesting possible steps that may lead to improvement in colposcopic accuracy.

Carcinoma in Situ↗
PubMed2006

Age-related changes of the cervix influence human papillomavirus type distribution.

Approximately 15 human papillomavirus (HPV) types cause virtually all cervical cancer whereas other HPV types are unrelated to cancer. We were interested in whether some noncarcinogenic types differ from carcinogenic in their affinity for the cervical transformation zone, where nearly all HPV-induced cancers occur. To examine this possibility, we tested cervical specimens from 8,374 women without cervical precancer and cancer participating in a population-based study in Guanacaste for >40 HPV types using PCR. We compared age-group specific prevalences of HPV types of the alpha9 species, which are mainly carcinogenic and include HPV16, to the genetically distinct types of the alpha3/alpha15 species (e.g., HPV71), which are noncarcinogenic and common in vaginal specimens from hysterectomized women. We related HPV detection of each group to the location of the junction between the squamous epithelium of the ectocervix and vagina and the columnar epithelium of the endocervical canal. Models evaluated the independent effects of amount of exposed columnar epithelium (ectopy) and age on the presence of alpha9 or alpha3/alpha15 types. Prevalence of alpha9 types (7.6%) peaked in the youngest women, declined in middle-aged women, and then increased slightly in older women. By contrast, prevalence of alpha3/alpha15 types (7.6%) tended to remain invariant or to increase with increasing age. Detection of alpha9 infections increased (P(trend) < 0.0005) but alpha3/alpha15 infections decreased (P(trend) < 0.0005) with increasing exposure of the columnar epithelia. Older age and decreasing cervical ectopy were independently positively associated with having an alpha3/alpha15 infection compared with having an alpha9 infection. These patterns need to be confirmed in other studies and populations. We suggest that these genetically distinct groups of HPV types may differ in tissue preferences, which may contribute to their differences in carcinogenic potential.

Adult↗
PubMed2006

Home Study Course: Spring 2006.

OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or practitioner who is seeking to develop or enhance his or hercolposcopic skills. The goal of the course is to present colposcopic cases that are unusual or instructive in terms of appearance, presentation, or management or to present colposcopic cases that demonstrate new and important knowledge in the area of colposcopyor pathology. Participants may benefit from reading and studying the material or from testing their knowledge by answering the questions. ACCME ACCREDITATION: The American Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The ASCCP designates this continuing medicaleducation activity for 1 hour category 1 credit of the ASCCP's Program for Continuing Professional Development and the Physician's Recognition Award of the American Medical Association. Credit is available for those who choose to apply. The Home Study Course is planned and produced in accordance with the ACCME's Essential Areas and Elements. DISCLOSURE: Faculty must disclose any significant financial interest or relationship with proprietary entities that may have a directrelationship to the subject matter. For this course, the author had no such relationship to report.

Adult↗
PubMed2006

Number of cervical biopsies and sensitivity of colposcopy.

OBJECTIVE: To examine the influence that type of medical training and number of biopsies have on sensitivity of colposcopically guided biopsies. METHODS: Among 408 women with an adequate enrollment colposcopy and a diagnosis of cervical intraepithelial neoplasia (CIN) 3 or cancer (CIN 3+) over 2 years in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions (ASCUS-LSIL) Triage Study, we evaluated factors influencing the sensitivity of the enrollment colposcopic procedure. We used contingency table analysis to examine confounding variables and chi(2) tests to ascertain statistical significance. RESULTS: Overall, 69.9% of women with a cumulative diagnosis of CIN 3+ had a "true-positive" enrollment colposcopically guided biopsy result of CIN 2 or worse (CIN 2+), the threshold that would trigger excisional therapy. The sensitivity of the procedure did not vary significantly by type of colposcopist. However, the sensitivity was significantly greater when the colposcopists took two or more biopsies instead of one (P<.01), a pattern observed across all types of colposcopists. Independent of the severity of the colposcopic impression, the frequency with which colposcopists took two or more biopsies instead of one varied (in descending order) from nurse practitioners to general gynecologists to gynecologic oncology fellows to gynecologic oncologists (P<.01). CONCLUSION: Colposcopy with guided biopsy or biopsies detects approximately two thirds of CIN 3+. Although the sensitivity of the procedure does not differ significantly by type of medical training, it is greater when two or more biopsies are taken.

Adolescent↗
PubMed2006

Preparing digitized cervigrams for colposcopy research and education: determination of optimal resolution and compression parameters.

OBJECTIVE: Visual assessment of digitized cervigrams through the Internet needs to be optimized. The National Cancer Institute and National Library of Medicine are involved in a large effort to improve colposcopic assessment and, in preparation, are conducting methodologic research. MATERIALS AND METHODS: We selected 50 cervigrams with diagnoses ranging from normal to cervical intraepithelial neoplasia 3 or invasive cancer. Those pictures were scanned at 5 resolution levels from 1,550 to 4,000 dots per inch (dpi) and were presented to 4 expert colposcopists to assess image quality. After the ideal resolution level was determined, pictures were compressed at 7 compression ratios from 20:1 to 80:1 to determine the optimal level of compression that permitted full assessment of key visual details. RESULTS: There were no statistically significant differences between the 3,000 and 4,000 dpi pictures. At 2,000 dpi resolution, only one colposcopist found a slightly statistically significant difference (p = 0.02) compared with the gold standard. There was a clear loss of quality of the pictures at 1,660 dpi. At compression ratio 60:1, 3 of 4 evaluators found statistically significant differences when comparing against the gold standard. CONCLUSIONS: Our results suggest that 2,000 dpi is the optimal level for digitizing cervigrams, and the optimal compression ratio is 50:1 using a novel wavelet-based technology. At these parameters, pictures have no significant differences with the gold standard.

Biomedical Research↗
PubMed2006

Digital tools for collecting data from cervigrams for research and training in colposcopy.

Colposcopy is a critical part of gynecologic practice but has documented deficiencies, including lack of correlation between the colposcopic appearance and the severity of underlying neoplasia, limited reproducibility, and difficulty in the optimal placement of colposcopically directed biopsies. In a collaborative effort to improve colposcopy, we are analyzing digitized cervigram images from National Cancer Institute-funded studies. Specifically, the National Cancer Institute has collected close to 100,000 cervigrams, digitized to create a database of images of the uterine cervix for research, training, and education. In addition to the cervigram images, this database contains clinical, cytologic, and molecular information at multiple examinations of 15,000 women, with password and ID labeling strategies to protect patient privacy. The National Library of Medicine has designed two web-accessible software tools. The Boundary Marking Tool allows experts on colposcopy to perform an evaluation of the pictures and to mark boundary regions of normal and abnormal regions of the uterine cervix; these evaluations are collected and saved in the database. The Multimedia Database Tool enables retrieval of test and image biomedical data according to specific queries, for example, all women with cervical intraepithelial neoplasia 3 whose cytologic results are atypical squamous cells of undetermined significance. The resource soon will be available as an open resource, via a teaching tool coordinated by a database manager, which will permit a variety of applications for teaching and research. In this article, we describe the perceived need for the resource and its components.

Biomedical Research↗
PubMed2005

Determinants of human papillomavirus-negative, low-grade squamous intraepithelial lesions in the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions triage study (ALTS).

BACKGROUND: Although low-grade squamous intraepithelial lesions (LSIL) most often are the result of infection by human papillomaviruses (HPV), a small proportion of women with LSIL have negative HPV tests. Using the Atypical Squamous Cells of Undetermined Significance/LSIL Triage Study (ALTS) population, the authors evaluated the significance of HPV-negative LSIL. METHODS: Women with cytologic interpretations of LSIL by referral Papanicolaou (Pap) tests or enrollment ThinPrep tests (range, 1195-1476 women, depending on the specimen type and the reviewer) had HPV testing performed by both Hybrid Capture 2 and polymerase chain reaction (PCR)-based linear array for 27 HPV types. RESULTS: Using 4 independent cytologic definitions of LSIL, only 3-11% of women with LSIL were found to have HPV-negative results on both HPV tests. The demographic characteristics of women with HPV-negative LSIL were consistent with those of a low-risk population; many were age > 35 years, and many reported no or only 1 recent sexual partner. The absolute risk of a histologic diagnosis of cervical intraepithelial neoplasia (CIN) Grade 3/carcinoma during the 2-year trial was lower for women with HPV-negative LSIL (range, 2-4%) compared with the absolute risks for oncogenic HPV-positive women with LSIL (range, 13-19%). However, at the next 6-month follow-up visit, 12%-32% of the women with HPV-negative LSIL had a positive HPV test. Finally, visual inspection of cervigrams demonstrated a clear association between a larger os and negative HPV test results compared with women who had HPV-positive LSIL. This may have influenced HPV sample adequacy. CONCLUSIONS: Based on the ALTS data, the authors found no evidence to support the existence of HPV-negative LSIL as a distinct biologic entity related to the risk of cervical carcinoma. Such results appear to represent cytologic misinterpretations or falsely negative HPV tests.

Adult↗
PubMed2005

Does the interval between papanicolaou tests influence the quality of cytology?

BACKGROUND: It is commonly believed that the sensitivity of Papanicolaou (Pap) tests decreases with a short interval between cytology samplings. To the authors' knowledge, there is only limited evidence to support this belief. METHODS: For 5055 women in the Atypical Squamous Cells of Undetermined Significance (ASCUS)-Low Grade Squamous Intraepithelial Lesion (LSIL) Triage Study (ALTS), the Pap interval was defined as the number of days between the referral Pap smear demonstrating ASCUS or LSIL ("first cytology") and the enrollment liquid-based ("repeat") cytology. The authors investigated the influence of the interval between Pap smears on repeat cytology by examining percentages of abnormal findings, cellularity, and test sensitivity among women diagnosed with histologic grade 3 cervical intraepithelial neoplasia (CIN3) during the 2-year course of the ALTS. In addition, because human papillomavirus (HPV) DNA adjunct testing is now performed, the authors evaluated HPV viral load, which was assayed using residual liquid cytology specimens, in women with CIN3. RESULTS: The Pap interval ranged from 8-30 days in 763 women, 31-60 days in 2317 women, 61-90 days in 1090 women, 91-120 days in 491 women, and 121-184 days in 394 women (mean of 61.3 days; standard deviation of 34 days). Repeat cytologic interpretations of unsatisfactory findings, ASCUS, and high-grade squamous intraepithelial lesion (HSIL) did not appear to vary among the Pap interval groups. However, low-grade cytologic regression occurred with an increasing Pap interval; negative cytology increased from 28.3% (8-30 days) to 41.6% (121-184 days) (P < 0.0001) whereas LSIL cytology decreased (P trend = 0.002). The approximate cellularity of the samples was slightly better in the interval group of 8-30 days (P trend = 0.04). Among women with CIN3, the repeat test sensitivity at a threshold of ASCUS or greater and the HPV DNA viral load was not found to vary by Pap interval (P trend = 0.80 and P trend = 0.36, respectively). CONCLUSIONS: The authors concluded that a short Pap interval (range, 15-120 days) does not significantly affect the quality of liquid-based repeat cytology, nor the viral load tested from a residual liquid-based specimen.

Adult↗
PubMed2005

The distribution of neoplasia arising on the cervix: results from the ALTS trial.

OBJECTIVE: This study was undertaken to evaluate the topographic distribution of precancerous intraepithelial lesions on the cervix. STUDY DESIGN: We studied the distribution of cervical biopsies and location of acetowhite lesions as determined by cervigrams among women who underwent a colposcopic examination and biopsy during the ASCUS-LSIL Triage Study (ALTS). RESULTS: More biopsies were taken in the 12 o'clock (41.4%) and 6 o'clock (28.4%) quadrants than in 3 o'clock and 9 o'clock quadrant (15.8% and 14.5%, respectively) (P<.001). The proportion of abnormal histology per biopsy, and the grade of neoplasia, did not vary significantly by position. Cervigrams demonstrated visible intraepithelial lesions and acetowhitening more common on the anterior and posterior quadrants of the cervix. CONCLUSION: More cervical intraepithelial neoplasia might develop at the anterior and posterior lips of the cervix. However, the evidence is weak and confounded by a tendency of the anterior and posterior quadrants to be acetowhite even in the absence of cervical intraepithelial neoplasia.

Adolescent↗
PubMed2005

Visual inspection with acetic acid for cervical cancer screening outside of low-resource settings.

OBJECTIVES: To assess visual inspection with acetic acid (VIA) as a screening tool for use in a well-equipped health center in Peru, to evaluate VIA as an alternative or adjunct to the Papanicolaou (Pap) smear, and to determine if VIA can play a role in settings other than low-resource ones. METHODS: This was a prospective study of 1 921 asymptomatic women living in Lima, Peru, carried out in 1999 and 2000. The study was performed at a cancer center equipped with the latest-generation technology and highly trained oncologists. The women underwent a complete clinical evaluation, including a Pap smear and VIA. Participants with any positive test were referred for colposcopy and biopsy. RESULTS: More women tested positive by VIA than on the Pap smear (6.9% vs. 4.2%; P = 0.0001). There were 35 women with histologic cervical intraepithelial neoplasia grade 1 (CIN 1); of these, 15 were detected by Pap and 20 by VIA (P = 0.4). A diagnosis of CIN 2 or 3 (CIN 2-3) was confirmed in a total of 13 cases; Pap detected 5 of the cases and VIA 11 of the cases (P = 0.06). The positive predictive value for detection of CIN 2+ was 8.3% for VIA and 6.3% for Pap (P = 0.5). Most importantly, while only 2.3% of patients with a positive VIA were lost to follow-up before colposcopy, that was true for 26.3% of the women with a positive Pap smear (P < 0.0001). CONCLUSIONS: VIA is useful for detection of precursor lesions of cervical cancer not only in low-resource settings but also in well-equipped health centers and cancer centers. In these non-low-resource settings, VIA has a positive predictive value comparable to the conventional Pap smear, but it is more likely to achieve earlier diagnosis, follow-up, and treatment than cytology-based screening.

Acetic Acid↗
PubMed2004

A population-based study of vaginal human papillomavirus infection in hysterectomized women.

We compared point prevalences and determinants of human papillomavirus (HPV) DNA detection by testing enrollment vaginal specimens from hysterectomized women (n=569) and enrollment cervical specimens from nonhysterectomized women (n=6098) >or=30 years old, using MY09/MY11 L1 consensus-primer polymerase chain reaction. The subjects were participating in a population-based cohort study (n=10,049) in Guanacaste, Costa Rica, that was initiated in 1993. Non-cancer-associated HPV types, especially types 61, 71, and 72, were detected more frequently in the vaginal specimens from hysterectomized women (23.7% [95% confidence interval [CI], 20.3%-27.4%]) than in the cervical specimens from nonhysterectomized women (16.7% [95% CI, 15.7%-17.6%]) (P=.0001). There was no difference between the prevalences of cancer-associated HPV types in hysterectomized women and those in nonhysterectomized women; in both groups, the prevalence of HPV DNA was greater in women with multiple lifetime sex partners. We infer from our data that the cervical transformation zone may not be needed for cancer-associated HPV infection but may be uniquely susceptible to HPV-induced carcinogenesis; we also infer that specific phylogenetic groups of HPV (i.e., A3/A4/A15) may have a predilection for vaginal epithelium.

Adult↗
PubMed2003

Right-sided ectocervical lesions may be associated with false-negative cytology among women with histologic cervical intraepithelial neoplasia 2 or 3.

BACKGROUND: The association between the location of an ectocervical lesion and the sensibility of cytologic screening has not been adequately evaluated. METHODS: We evaluated the proportion of false-negative cytologic interpretations using three independent cytologic interpretations (conventional, PapNet, and ThinPrep) according to lesion location in 111 women with histologic cervical intraepithelial neoplasia 2 or 3 of a population-based study of cervical neoplasia conducted in Guanacaste, Costa Rica. Semiquantitative measures of human papillomavirus viral load were also considered. RESULTS: Lesions on a women's right ectocervix were associated with more frequent false-negative results than lesions on left ectocervix for each of the cytologic methods or when the most severe interpretation was considered (p = .004). Right-sided lesions had nonsignificantly lower viral loads than left-sided lesions (p = .2). CONCLUSIONS: Cervical intraepithelial neoplasia 2 or 3 located on the right side of the cervix may be poorly sampled with broom samplers in some settings, resulting in false-negative cytologic results.

Journal Article↗