Biomedical subjects

Mark Schiffman

Publications and source records attributed to Mark Schiffman.

At least 19 recordsLinked to original sources

PubMed2026

Longitudinal analysis of high-risk HPV infections reveals within-host viral genome changes over time.

Persistent infection with high-risk (HR)-HPV causes cervical cancer, however, it is unclear why most infections resolve while a minority progress. We deep sequenced the HPV genomes of 1,228 HR-HPV-positive serial samples from 351 women with persistent infections (2-10 serial samples per woman over 1-8 years), including 279 controls and 72 precancer/cancer cases, to assess HR-HPV genome changes during infection and relation to infection outcomes. Seventy-seven percent of persistent infections (45-97% by HPV type) were infections with the same exact viral genome isolate; for HPV16, only 52% were persistent with the same isolate. This may suggest some infections include a type-specific isolate switch or new isolate infection during persistence. We additionally observed within-host change to the HPV genome estimated as gradual changes to intrahost single nucleotide variant (iSNV) frequency, and changes varied by HPV type, with HPV33 infections showing the most iSNV changes. Cases exhibited fewer viral genome changes during infection compared to controls (OR = 0.31, 95% CI = 0.1 - 0.86, p = 0.019), suggesting a more stable and clonal viral genome in cases. By viral gene, E7 had fewer nonsynonymous mutations in the cases compared to controls that cleared within 2 years of infection (p = 0.012), which confirms the importance of E7 conservation and suggests mutations to E7 reduce persistence associated with progression. There was a similar pattern in E4 (p = 0.013), while E5 had more changes in the cases (p = 0.008). A subset of 28 infections had an intervening HPV-negative sample between HPV-positive visits; 93% of these infections had the same exact viral genome isolate in the samples before and after the negative, consistent with subclinical persistence and subsequent re-detection. Our data suggests that HR-HPV type-persistence can include a collection of viral isolates, and viral mutations during infection, particularly in E7, reduce HR-HPV persistence and thus carcinogenic potential.

Humans↗

PubMed2007

The Bethesda Interobserver Reproducibility Study (BIRST): a web-based assessment of the Bethesda 2001 System for classifying cervical cytology.

BACKGROUND: The Bethesda System (TBS) along with its companion atlas was updated in 2001 to improve standardization, clarity, and reproducibility of cervical cytology reporting. METHODS: The authors used a novel web-based format to compare assessments of 77 images demonstrating a range of classical and borderline cytologic changes by a self-selected group of United States cytotechnologists (n = 216) and pathologists (n = 185). RESULTS: Participants were highly experienced, with 71.2% of cytotechnologists and 53.0% of pathologists reporting >10 years of practice. The mean percentage of exact agreement with the panel was slightly though significantly higher for cytotechnologists (57.0%) compared with pathologists (53.4%), adjusted for experience (P = .004); cervical cytology percentage effort (P = .0005); or cervical accession volume (P = .0002). Compared with the TBS panel, exact agreement was achieved for 55.1% of image ratings compared with 82.3% agreement at the level of Negative vs non-Negative for images with a single-panel interpretation. Agreement with the panel was highest for images classified as Low-Grade Squamous Intraepithelial Lesion and lowest for Atypical Squamous Cells qualified as either of Undetermined Significance or Cannot Exclude a High-Grade Squamous Intraepithelial Lesion. Reviewers were less sensitive in identifying high-grade glandular lesions than they were in identifying high-grade squamous lesions at any threshold (P < .001). CONCLUSIONS: Morphologic appearances of images were more important determinants than participants' academic or professional degrees with regard to interobserver reproducibility in classifying cervical cytology images. Experienced cytotechnologists and pathologists performed similarly. Participants achieved higher sensitivity for identifying high-grade squamous lesions than they did for high-grade glandular lesions. These findings demonstrated that web-based studies may be useful in assessing interobserver agreement in classifying images.

Adenocarcinoma↗

PubMed2007

Viral determinants of human papillomavirus persistence following loop electrical excision procedure treatment for cervical intraepithelial neoplasia grade 2 or 3.

BACKGROUND: Persistent infection with carcinogenic human papillomavirus (HPV) causes cervical precancer (cervical intraepithelial neoplasia grade 2+) which, in the United States, is commonly treated using the loop electrical excision procedure (LEEP). Data from Atypical Squamous Cells of Undetermined Significance-Low-Grade Squamous Intraepithelial Lesion Triage Study were used to evaluate HPV persistence and reappearance after LEEP. METHODS: Cervical specimens, collected before LEEP and at 6-month study visits, were tested by L1-PCR for detection of >or=27 HPV types. HPV persistence, defined as the same HPV type being present before and 6 months after LEEP, was evaluated by: (a) genotype, (b) carcinogenicity, and (c) phylogenetic species. HPV infections that cleared post-LEEP (the complement of persistence) were followed for reappearance of the same type. RESULTS: HPV infections (n = 1,130) were detected among 481 women who underwent LEEP. Overall, 20.4% [95% confidence interval (95% CI), 18.2-22.9%] of infections persisted. Assessment of heterogeneity within the three categorizations of HPV showed that phylogenetic species best fit the data. Persistence was significantly greater by HPV types in the alpha3 species [all are noncarcinogenic; 40.9% (95% CI, 31.8-50.4%)] compared with HPV types in the alpha9 (HPV16 and related types) and alpha7 species (HPV18 and related types; 17.6% and 17.9%, respectively; P < 0.001 for both). HPV reappeared in 7.8% (95% CI, 6.1-9.9%) of infections that cleared after LEEP. Infections in the alpha3 species (22.6%) were the most likely to reappear compared with HPV types in the alpha9 (7.5%) and alpha7 (6.8%) species. CONCLUSIONS: Patterns of HPV persistence and reappearance following LEEP were better explained by phylogenetic rather than standard classifications. HPV types likely to persist after LEEP as well as those likely to repopulate the cervical/vaginal epithelium were those in the alpha3 species, which are in effect not treated, but are not associated with cervical cancer and are unlikely to cause disease.

Electrosurgery↗

PubMed2006

Human papillomavirus (HPV) types 101 and 103 isolated from cervicovaginal cells lack an E6 open reading frame (ORF) and are related to gamma-papillomaviruses.

Complete genomes of HPV101 and HPV103 were PCR amplified and cloned from cervicovaginal cells of a 34-year-old female with cervical intraepithelial neoplasia grade 3 (CIN 3) and a 30-year-old female with a normal Pap test, respectively. HPV101 and HPV103 contain 4 early genes (E7, E1, E2, and E4) and 2 late genes (L2 and L1), but both lack the canonical E6 ORF. Pairwise alignment similarity of the L1 ORF nucleotide sequences of HPV101 and HPV103 indicated that they are at least 30% dissimilar to each other and all known PVs. However, similarities of the other ORFs (E7, E1, E2, and L2) indicated that HPV101 and HPV103 are most related to each other. Phylogenetic analyses revealed that these two types form a monophyletic clade, clustering together with the gamma- and pi-PV groups. These data demonstrated that HPV genomes closely related to papillomaviruses identified from cutaneous epithelia can be isolated from the genital mucosal region. Moreover, this is the first report of HPVs lacking an E6 ORF and phylogenetic evidence suggests this occurred subsequent to their emergence from the gamma-/pi-PVs.

Adult↗

PubMed2006

Persistent human papillomavirus infection is associated with a generalized decrease in immune responsiveness in older women.

The development of cervical cancer and its precursors are linked to persistent infection with oncogenic types of human papillomavirus (HPV). Host immune responses seem to be determinants of risk for this disease. However, little is known about the immunologic determinants of HPV persistence. Here, we examined the association between lymphoproliferative responses to antigens/mitogens and persistent HPV infection in women older than 45 years. Women included in this study were participants in a 10,000-woman population-based cohort study of cervical neoplasia in Costa Rica. Women older than 45 years and HPV DNA positive at a screening visit were selected as cases (n = 283). We selected a comparably sized control group of HPV DNA-negative women, matched to cases on age and time since enrollment (n = 261). At an additional clinical visit, women were cytologically and virologically rescreened, and cervical and blood specimens were collected. Proliferative responses to phytohemagglutinin (PHA), influenza virus (Flu), and HPV16 virus-like particle (VLP) were lower among women with persistent HPV infection [median counts per minute (cpm): 72,849 for PHA, 1,241 for Flu, and 727 for VLP] than for the control group (median cpm: 107,049 for PHA, 2,111 for Flu, and 2,068 for VLP). The decreases were most profound in women with long-term persistence and were only observed for the oldest age group (>/=65 years). Our results indicate that an impairment in host immunologic responses is associated to persistent HPV infection. The fact that effects were evident for all studied stimuli is suggestive of a generalized effect.

Age Factors↗

PubMed2006

Human papillomavirus prevalence in women who have and have not undergone hysterectomies.

We compared human papillomavirus (HPV) prevalence in an age-stratified random sample of women who have undergone a hysterectomy (WH) (n=573) with the HPV prevalence in age-matched women with intact cervices (women who have not undergone a hysterectomy [WNH]) (n=581) participating in a study at Kaiser Permanente in Portland, Oregon. Testing cervicovaginal lavage fluids for >40 HPV genotypes using an MY09/11 L1 consensus primer polymerase chain reaction method, we found no statistical differences in the prevalence of HPV (16% for WNH vs. 13.9% for WH) or carcinogenic HPV (6.5% for WNH vs. 4.5% for WH) between the 2 groups of women. Although WH have a similar prevalence of carcinogenic HPV infection, compared with WNH without a cervix, they have minimal risk of HPV-induced cancer and are unlikely to benefit from HPV testing.

Adult↗

PubMed2006

Comparison of human papillomavirus distribution in cytologic subgroups of low-grade squamous intraepithelial lesion.

BACKGROUND: Low-grade squamous intraepithelial lesion (LSIL) subsumes the formerly delineated cytologic categories of human papillomavirus (HPV)-associated cell changes (koilocytotic atypia) and low-grade dysplasia/cervical intraepithelial neoplasia (CIN) Grade 1 (CIN1). In this study, the objective was to determine whether these 2 morphologic subcategories are characterized by differences in risk for CIN3 and/or HPV type distribution. METHODS: Within the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study, all cytologic interpretations of HPV cellular changes and CIN1 rendered by any of the pathology reviewers (community laboratory, clinical center, or Pathology Quality-Control Group) on referral Papanicolaou (Pap) tests or enrollment ThinPrep Pap tests were included for analysis. HPV testing was performed by Hybrid Capture 2 (HC2) and by polymerase chain reaction based reverse-line blot analysis for 27 HPV types. The absolute risks of cumulative detection of CIN3 or cancer (CIN3 +) and CIN2 or worse (CIN2 +) over 2 years of follow-up were calculated for the various cytologic interpretations. RESULTS: For each review group and cytology preparation, most LSIL interpretations (from approximately 2 of 3 interpretations to 3 of 4 interpretations) were subcategorized as CIN1 rather than HPV cellular changes. HPV type 16 (HPV-16) was the most common HPV type and was identified in 21% to 24% of CIN1 and in 14% to 18% of HPV cellular changes. Nononcogenic types were identified alone in from 9% to 11% of CIN1 compared with 17% to 20% of HPV cellular change. The absolute risks of CIN1 and HPV cellular changes for cumulatively detected CIN3 + ranged from 12% to 16% for CIN1 and from 6% to 9% for HPV cellular changes. CONCLUSIONS: Both cytologic subcategories of LSIL were associated predominantly with oncogenic HPV types; however, the proportion of nononcogenic HPV types was lower and the absolute risks for CIN3 + were higher for CIN1 compared with HPV cellular changes. The concordance in subcategorizing LSIL was low, and the authors concluded that the diagnostic distinction is of limited clinical utility for individual patient management.

Female↗

PubMed2006

Relationships of human papillomavirus type, qualitative viral load, and age with cytologic abnormality.

Persistent cervical infections with carcinogenic human papillomaviruses (HPV) cause virtually all cervical cancer. Cytologic abnormalities are the manifestations of HPV infections used to identify women at risk. To compare the potential of the full range of anogenital HPV genotypes to induce cytopathic effects, we examined the influences of HPV type, viral load, and age on cytopathology among 1,222 women having a single HPV type at enrollment into a 10,000-woman population-based study in Costa Rica. Cervical specimens were tested for approximately 40 HPV types by MY09/MY11 L1 primer PCR and type-specific dot blot hybridization. Types were organized by phylogenetic species and cancer risk. PCR signal strength served as a qualitative surrogate for viral load. Overall, 24.8% [95% confidence interval (95% CI), 22.4-27.3] of single prevalent HPV infections had concurrent abnormalities (atypical squamous cells or worse) ranging from 0.0% to 80.0% based on HPV type. Noncarcinogenic alpha3/alpha15 types, although highly prevalent, uncommonly caused cytologic abnormalities (13.1%; 95% CI, 9.8-17.0). In contrast, one quarter to nearly one half of infections with a single major carcinogenic species type (alpha9/alpha11/alpha7/alpha5/alpha6) produced abnormalities. Greater abnormalities were observed with increasing qualitative viral load of carcinogenic types; fewer abnormalities were observed among older women (>54 years). A high percentage (46.2%) of detected abnormalities in women infected with HPV16 or related alpha9 types were high grade or worse, consistent with strong carcinogenicity, compared with 10.7% in women infected with alpha7 types, including HPV18, a major cause of adenocarcinoma. The lack of evident severe abnormalities associated with HPV18 and related HPV types might have implications for screening for poorly detected glandular and alpha7-related lesions.

Adult↗

PubMed2006

Human papillomavirus genotypes and the cumulative 2-year risk of cervical precancer.

BACKGROUND: Prospective data on the risks of cervical precancer associated with specific human papillomavirus (HPV) genotypes are limited. METHODS: In 5060 women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS), we determined the cumulative 2-year risks of cervical intraepithelial neoplasia (CIN) grade 2 or more severe (> or =CIN2) and of grade 3 or more severe (> or =CIN3) for 38 individual HPV genotypes, as detected by polymerase chain reaction. RESULTS: The most common HPV genotypes detected at baseline, in descending order of prevalence, were 16, 52, 51, 31, 18, 53, 39, 56, 62, 59, and 58. When detected as a single-type HPV infection, HPV-16 had a 2-year cumulative risk of 50.6% (95% confidence interval [CI], 44.1%-57.2%) for > or =CIN2 and 39.1% (95% CI, 32.9%-45.7%) for > or =CIN3. For other singly detected carcinogenic HPV types, the risk of > or =CIN2 ranged from 4.7% (for HPV-59) to 29.5% (for HPV-31), and the risk of > or =CIN3 ranged from 0.0% (for HPV-59) to 14.8% (for HPV-31). Multiple infections with HPV genotypes of different risk classes resulted in a risk that was similar to, and not significantly different from, the risk observed for the HPV genotype of the highest risk class. CONCLUSIONS: Genotype-specific HPV testing may be useful for identifying women with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions who are at higher and lower risk of prevalent and incipient cervical precancer.

Colposcopy↗

PubMed2006

Chapter 5: Updating the natural history of HPV and anogenital cancer.

The major steps in cervical carcinogenesis include infection of the metaplastic epithelium of the cervical transformation zone with one or more of the 12-18 carcinogenic types of human papillomavirus (HPV) infection, viral persistence, clonal progression of the persistently-infected epithelium to cervical precancer, and invasion. Although these fundamental steps are established, several new epidemiologic studies have shed light on the factors that influence each of these transitions. The importance of the transformation zone in cervical cancer has been extended to other HPV-induced cancers such as anal or tonsillar cancers. Natural history studies show that HPV with normal cervical cytology and cervical intraepithelial neoplasia (CIN) grade 1 behave similarly, with the majority of both showing regression. Although these studies have demonstrated the importance of HPV persistence in the development of precancer CIN-3, the timing from infection to evidence of CIN-3 varies from 1 to 10 years. Whether equivalent lesions diagnosed later differ in their natural history remains unknown. Several factors have been implicated in enhancing persistence and/or progression. However, none are consistently associated with both except age: young women are less likely to show persistence and older women with persistence are more likely to be at risk of invasive cancer. Recent studies have also underscored the importance of the host immune response in clearance of established infections. Finally, data on non-cervical HPV infections, such as penile infections are limited to date compared to cervical infections. Several ongoing cohort studies should give us further insight into male infections in the near future.

Age Factors↗

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

Cost-effectiveness analysis based on the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion Triage Study (ALTS).

BACKGROUND: The ALTS (atypical squamous cells of undetermined significance [ASCUS] and low-grade squamous intraepithelial lesion [LSIL] Triage Study) suggests that, for women diagnosed with ASCUS, human papillomavirus (HPV) DNA testing followed by referral to colposcopy of only those women with oncogenic HPV (i.e., HPV DNA testing) is as effective at detecting cervical intraepithelial neoplasia (CIN) 3 or cancer (CIN3+) as referring all women with ASCUS for immediate colposcopy. We conducted a cost-effectiveness analysis of the ALTS trial to determine whether HPV DNA testing is a cost-effective alternative to immediate colposcopy or conservative management with up to three cytology examinations. METHODS: Data from the ALTS trial were used in conjunction with medical care costs in a short-term decision model. The model compared the incremental costs per case of CIN3+ detected as measured by the incremental cost-effectiveness ratio (ICER) for the following management strategies for women with ASCUS: immediate colposcopy, HPV DNA testing, and conservative management with up to three cytology examinations. RESULTS: The least costly and least sensitive strategy was conservative management with one repeat cytology examination using a threshold of high-grade squamous intraepithelial lesion (HSIL) for referral to colposcopy. Compared with this strategy, triage to colposcopy based on a positive HPV DNA test result had an ICER of 3517 dollars per case of CIN3+ detected. Immediate colposcopy and conservative management with up to three repeat cytology visits detected fewer cases of CIN3+ and were more costly than HPV DNA testing. Immediate colposcopy became cost-effective at 20,370 dollars compared with HPV DNA testing only if colposcopy and biopsy were assumed to be 100% sensitive. CONCLUSIONS: HPV DNA testing is an economically viable strategy for triage of ASCUS cytology. The less than perfect sensitivity of colposcopy and biopsy needs to be accounted for in future clinical guidelines and policy analyses.

Adult↗

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

When to test women for human papillomavirus.

Explore the source record for details and available documents.

Female↗

PubMed2006

Predicting absolute risk of CIN3 during post-colposcopic follow-up: results from the ASCUS-LSIL Triage Study (ALTS).

OBJECTIVE: At present, clinical management of women referred to colposcopy but found to have <CIN2 remains unclear. Using data from the ASCUS-LSIL Triage Study (ALTS) to inform clinical management, we calculated the absolute risk for developing CIN3 within 2 years of referral to an enrollment colposcopy. STUDY DESIGN: Women included in the analyses: (1) were initially referred to ALTS with a community cytologic interpretation of atypical squamous cell of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL); (2) had a colposcopic evaluation and biopsy, if indicated, resulting in a diagnosis <CIN2; and, therefore (3) were followed without treatment. Results from subsequent human papillomavirus (HPV) testing, liquid-based cytology interpretations, and a second colposcopic evaluation at least 6 months after and within 2 years of the first colposcopic evaluation were used to calculate absolute risks for CIN3. RESULTS: Women with HPV-negative test results were at low risk for CIN3 regardless of other test results. Among HPV-positive women, increasing absolute risks of CIN3 were observed with increasing cytology severity: 7% (normal), 11% (ASCUS and LSIL), and 45% (HSIL). The highest absolute risk for CIN3 (67%) was observed for HPV-positive women with HSIL and a colposcopic impression of high-grade/cancer on the second colposcopy. CONCLUSION: In the ALTS population, after the first colposcopic diagnosis of <CIN2, clear risk stratification for CIN3 outcomes was obtained among women with a subsequent HPV-positive test. Because absolute risk for histologic CIN3 outcomes was high for women with HPV positive tests, HSIL cytology, and a high-grade impression at second colposcopy, it is worth considering whether this combination of findings might warrant immediate excisional therapy in some circumstances.

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↗