Recombinant human serum amyloid P in healthy volunteers and patients with pulmonary fibrosis.

PRM-151, recombinant human Pentraxin-2 (PTX-2) also referred to as serum amyloid P (SAP), is under development for treatment of fibrosis. A First-in-Human (FIH) trial was performed to assess the safety, tolerability, and pharmacokinetics of single ascending intravenous doses of PRM-151 administered to healthy subjects, using a randomized, blinded, placebo controlled study design. Each cohort included three healthy subjects (PRM-151:placebo; 2:1). SAP levels were assessed using a validated ELISA method, non-discriminating between endogenous and exogenous SAP. At a dose level of 10 mg/kg, at which a physiologic plasma level of SAP was reached, two additional healthy volunteers and three pulmonary fibrosis (PF) patients were enrolled enabling comparison of the pharmacokinetic SAP profile between healthy volunteers and PF patients. In addition, the percentage of fibrocytes (CD45+/Procollagen-1+ cells) in whole blood samples was assessed to demonstrate biological activity of PRM-151 in the target population. PRM-151 administration was generally well tolerated. In two pulmonary fibrosis patients non-specific, transient skin reactions (urticaria and erythema) were observed. PRM-151 administration resulted in a 6-to 13-fold increase in mean baseline plasma SAP levels at dose levels of 5, 10, and 20 mg/kg. The estimated t1/2 of PRM-151 in healthy volunteers was 30 h. Pharmacokinetic profiles were comparable between healthy volunteers and PF patients. PRM-151 administration resulted in a 30-50% decrease in fibrocyte numbers 24 h post-dose. This suggests that administration of PRM-151 may be associated with a reduction of fibrocytes in PF patients, a population for which current pharmacotherapeutic options are limited. The pharmacological action of PRM-151 should be confirmed in future research.

Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in women aged 15-25 years with and without serological evidence of previous exposure to HPV-16/18.

In the Phase III PATRICIA study (NCT00122681), the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix(®), GlaxoSmithKline Biologicals) was highly efficacious against HPV-16/18 infections and precancerous lesions in women HPV-16/18 deoxyribose nucleic acid (DNA) negative and seronegative at baseline. We present further data on vaccine efficacy (VE) against HPV-16/18 in the total vaccinated cohort including women who may have been exposed to HPV-16/18 infection before vaccination. In women with no evidence of current or previous HPV-16/18 infection (DNA negative and seronegative), VE was 90.3% (96.1% confidence interval: 87.3-92.6) against 6-month persistent infection (PI), 91.9% (84.6-96.2) against cervical intraepithelial neoplasia (CIN)1+ and 94.6% (86.3-98.4) against CIN2+ [97.7% (91.1-99.8) when using the HPV type assignment algorithm (TAA)]. In women HPV-16/18 DNA negative but with serological evidence of previous HPV-16/18 infection (seropositive), VE was 72.3% (53.0-84.5) against 6-month PI, 67.2% (10.9-89.9) against CIN1+, and 68.8% (-28.3-95.0) against CIN2+ [88.5% (10.8-99.8) when using TAA]. In women with no evidence of current HPV-16/18 infection (DNA negative), regardless of their baseline HPV-16/18 serological status, VE was 88.7% (85.7-91.1) against 6-month PI, 89.1% (81.6-94.0) against CIN1+ and 92.4% (84.0-97.0) against CIN2+ [97.0% (90.6-99.5) when using TAA]. In women who were DNA positive for one vaccine type, the vaccine was efficacious against the other vaccine type. The vaccine did not impact the outcome of HPV-16/18 infections present at the time of vaccination. Vaccination was generally well tolerated regardless of the woman's HPV-16/18 DNA or serological status at entry.

Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years.

BACKGROUND: Prophylactic human papillomavirus (HPV) vaccines have to provide sustained protection. We assessed efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. METHODS: Women aged 15-25 years, with normal cervical cytology, who were HPV-16/18 seronegative and oncogenic HPV DNA-negative (14 types) at screening participated in a double-blind, randomised, placebo-controlled initial study (n=1113; 560 vaccine group vs 553 placebo group) and follow-up study (n=776; 393 vs 383). 27 sites in three countries participated in the follow-up study. Cervical samples were tested every 6 months for HPV DNA. Management of abnormal cytologies was prespecified, and HPV-16/18 antibody titres were assessed. The primary objective was to assess long-term vaccine efficacy in the prevention of incident cervical infection with HPV 16 or HPV 18, or both. We report the analyses up to 6.4 years of this follow-up study and combined with the initial study. For the primary endpoint, the efficacy analysis was done in the according-to-protocol (ATP) cohort; the analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was done in the total vaccinated cohort (TVC). The study is registered with ClinicalTrials.gov, number NCT00120848. FINDINGS: For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95.3% (95% CI 87.4-98.7) and against 12-month persistent infection was 100% (81.8-100). Vaccine efficacy against CIN2+ was 100% (51.3-100) for lesions associated with HPV-16/18 and 71.9% (20.6-91.9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred. INTERPRETATION: Our findings show excellent long-term efficacy, high and sustained immunogenicity, and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. FUNDING: GlaxoSmithKline Biologicals (Belgium).

Human papillomavirus and HPV vaccines: a review.

Cervical cancer, the most common cancer affecting women in developing countries, is caused by persistent infection with "high-risk" genotypes of human papillomaviruses (HPV). The most common oncogenic HPV genotypes are 16 and 18, causing approximately 70% of all cervical cancers. Types 6 and 11 do not contribute to the incidence of high-grade dysplasias (precancerous lesions) or cervical cancer, but do cause laryngeal papillomas and most genital warts. HPV is highly transmissible, with peak incidence soon after the onset of sexual activity. A quadrivalent (types 6, 11, 16 and 18) HPV vaccine has recently been licensed in several countries following the determination that it has an acceptable benefit/risk profile. In large phase III trials, the vaccine prevented 100% of moderate and severe precancerous cervical lesions associated with types 16 or 18 among women with no previous infection with these types. A bivalent (types 16 and 18) vaccine has also undergone extensive evaluation and been licensed in at least one country. Both vaccines are prepared from non-infectious, DNA-free virus-like particles produced by recombinant technology and combined with an adjuvant. With three doses administered, they induce high levels of serum antibodies in virtually all vaccinated individuals. In women who have no evidence of past or current infection with the HPV genotypes in the vaccine, both vaccines show > 90% protection against persistent HPV infection for up to 5 years after vaccination, which is the longest reported follow-up so far. Vaccinating at an age before females are exposed to HPV would have the greatest impact. Since HPV vaccines do not eliminate the risk of cervical cancer, cervical screening will still be required to minimize cancer incidence. Tiered pricing for HPV vaccines, innovative financing mechanisms and multidisciplinary partnerships will be essential in order for the vaccines to reach populations in greatest need.

Analysis of acetic acid-induced whitening of high-grade squamous intraepithelial lesions.

Immature and dysplastic cervical squamous epithelium whitens after the application of acetic acid during a colposcopic examination. The whitening process occurs visually over several minutes and subjectively discriminates between dysplastic and normal tissue. In this work, examples of the acetowhitening process are detailed in three ways: the color-imaged colposcopic appearance of the acetowhitening of high-grade cervical intraepithelial neoplasia (CIN 2/3), the kinetics of these reflectance patterns transformed to reduce noise in the signal, and a self-normalized green to red ratio measurement of the kinetics of these reflectance patterns. A total of six patients with biopsy confirmed CIN 2/3 were examined to obtain a set of timed images tracking the acetowhitening and the whitening-decay process over the course of 5-10 min. Regions of normal mature squamous epithelium within the same patients were also followed as an internal control. We determined that the temporal change over a 10 min time period in the ratio of green to red light intensities, taken from the respective color channels of the CCD, provides a reliable measure to clearly distinguish CIN 2/3 from normal cervical epithelium. This imaging and data normalization procedure may be applied to cervical lesions of different grades, to determine if a quantitative estimate provides predictive value during the colposcopic diagnosis.

T-cell differentiation of human and non-human primate CD34+ hematopoietic progenitor cells using porcine thymic stroma.

Transplantation of swine thymic tissue has been proposed as an approach to reconstitute the immune system of HIV-infected individuals. This is an attractive strategy because miniature swine are readily available as donors and porcine tissue is resistant to infection with HIV-1. Demonstration that porcine thymus tissue supports primate T-cell differentiation is critical to the ultimate utility of this approach. Using a thymic stroma culture system we have previously described [Rosenzweig M, Marks DF, Zhu H et al. In vitro T lymphopoiesis of human and rhesus CD34+ progenitor cells. Blood 1996; 87: 4040], we demonstrate that porcine thymus tissue is able to promote the in vitro T-lymphocyte differentiation of both human and non-human primate hematopoietic progenitor cells. CD34+ hematopoietic progenitors differentiated into both double positive (CD4+CD8+) and single positive thymocytes expressing CD4 or CD8 alone. A polyclonal T-cell repertoire was evident. In addition, the T cells responded appropriately to mitogen and were permissive to infection with simian immunodeficiency virus (SIV). These data demonstrate the ability of porcine thymus to support T-cell differentiation of both human and non-human hematopoietic progenitor cells and support in vivo studies of transplantation of swine thymic tissue as a strategy for immune reconstitution in AIDS.

Self-reported desire to improve colposcopic impressions.

BACKGROUND: Women who participate in cervical cancer screening programs must have access to high quality colposcopy services when their cytology test are abnormal. The purpose of this project is to evaluate colposcopic services currently available in New Hampshire and whether colposcopy providers are willing to network to maintain and improve their colposcopic pattern recognition skills in order to improve their colposcopic correlations. METHODS: A survey was mailed to 1314 providers throughout New Hampshire. The survey ascertained the extent of current colposcopic services in New Hampshire through practitioner and practice demographics, the cervical procedures performed, the self-reported colposcopy skill level, and the self-reported quality of past colposcopic education. It also measured interest in networking with others to improve their colposcopic pattern recognition skills. RESULTS: The survey response rate was 62%. 145 of the 810 respondents (18%) are currently performing colposcopies, indicating a statewide potential colposcopy accommodation rate of 3.5 to 7 women per month per colposcopist. 57% of the physician assistants, 59% of the family physicians, 75% of the gynecologists and 100% of the nurse practitioners were interested in enhancing their colposcopic pattern recognition skills by networking through quarterly meetings. CONCLUSIONS: The crude accommodation rate for colposcopy appears sufficient for the women of New Hampshire although the geographic distribution of the colposcopists is unknown. A majority of the colposcopists were interested in networking to improve their colposcopic pattern recognition skills, which could improve patient care.

The natural history of cervical cryosurgical healing. The minimal effect of debridement of the cervical eschar [see comment].

BACKGROUND: Cryosurgery is a favored treatment method for cervical intraepithelial neoplasia (CIN) among family physicians, in part because it is inexpensive and requires the least technical training and skill. Although cervical cryosurgery has been used for more than 30 years, the natural history of the postprocedure process has never been described. The primary purpose of our study was to describe the natural history of the healing process after cervical cryosurgery. A secondary purpose was to determine the effect of mechanical debridement of the cervical eschar on the symptoms of healing. METHODS: We conducted a prospective multicentered trial in which women who had a histologic ally documented CIN lesion underwent cervical cryosurgery. Forty-six women were randomized to undergo eschar debridement at 48 hours after cryosurgey, and 38 women received standard care. All women were followed up and given preweighed sanitary pads for hydrorrhea (watery discharge) collection and a diary to record the severity and number of days of odor, pain, cramping, and hydrorrhea that were experienced. RESULTS: The average total amount of hydrorrhea or discharge was 288 g, which required using an average of 41 sanitary pads during a period of 12.4 days. The duration of odor was 8.9 days, and the pain and cramping experienced after cryosurgery lasted 4.7 days. Women who were obese had greater hydrorrhea and pad usage than nonobese women. Debridement of the cervical eschar did not significantly change the signs and symptoms of healing after cryosurgery. CONCLUSIONS: There are significant symptoms patients experience after cryosurgery that are not ameliorated by debridement. The expectations of the cryosurgical healing process should be disclosed to women before the procedure.

Healing experiences after cervical cryosurgery.

BACKGROUND: Treatment for cervical intraepithelial neoplasia with cryosurgery is uncomfortable for many women. The subsequent healing process is also thought to bring discomfort. The purpose of our study was to describe women's experiences after cryosurgery, and how obesity, age, and gravidity affected, the healing process. METHODS: We developed a survey from focus group results to measure the unpleasantness of hydrorrhea (watery discharge) from cryosurgery, the pad protection required, and the odor associated with the hydrorrhea. The cryosurgical experiences were compared with normal menses for the use and frequency of pad protection, medications used, and any activity restrictions. RESULTS: Cryosurgical experiences were unpleasant for 78.3% of the women because of the pain and cramping of the procedure and the resulting hydrorrhea, odor, and necessity of wearing pads for protection. These experiences after cryosurgery caused 38.6% to restrict their activities and 67.1% to take medications, a significantly greater proportion than the 16.9% whose activities were restricted normal menses and the 26.8% who took medications for normal menses (P=-.004, P <.001, respectively). In addition to these experiences, obese, multigravid, and older women were more bothered by the duration of wearing pads than their counterparts (P=.0246, =.0061, and P=.0159, respectively). CONCLUSIONS: Our study showed that the cryosurgical healing process was not pleasant, and was least tolerable for obese, multigravid, and older women. As many as 50% of women undergoing cryosurgery will perceive the hydrorrhea, its odor, and the wearing of pads to be worse than normal menses, especially if their menses are usually light.

The technical performance and clinical feasibility of telecolposcopy.

BACKGROUND: The purpose of our study was to demonstrate the technical performance and clinical feasibility of a telecolposcopic system through assessment of image transmission veracity, ease of office system implementation, and the patient's acceptance of the electronic image transmission. METHODS: We used a telecolposcopic system incorporating a custom software package that integrated patient history, current gynecologic status, epidemiologic risk factors, and colposcopic images for local medical documentation and transmission. Satisfaction questionnaires were developed to measure ease of implementation at the remote sites and the patients' acceptance of telecolposcopy. RESULTS: Seventy-nine women participated in our trial. From 3 to 20 images were captured for each woman, documenting cervical squamous intraepithelial lesions and vaginal and vulvar diseases. All images were received without distortions in color, size, or orientation. With complete visualization of the squamocolumnar junction there was an 86% agreement between the remote and review sites (kappa=.533, P=.019). The interobserver agreement for colposcopic impressions was 86% (kappa=.684, P <.001), and for colposcopic impressions with histology within one level of disease severity, 86% (kappa=.78, P <.001). Colposcopists' and patients' satisfaction with telecolposcopy was excellent. More than 95% of the women stated that they would rather have their colposcopy locally with electronic transmission if an experienced colposcopist were more than 25 miles away. CONCLUSIONS: The telecolposcopic system described in our study is technically feasible, can be implemented in an office system with limited technical support, and is preferred by women who have to travel many miles to receive referral health care.

Cost-effectiveness of the conventional papanicolaou test with a new adjunct to cytological screening for squamous cell carcinoma of the uterine cervix and its precursors.

OBJECTIVE: To estimate costs and outcomes of conventional annual Papanicolaou (Pap) test screening compared with biennial Pap test plus speculoscopy (PPS) screening for cervical neoplasms. DESIGN: A Markov model compared cost-effectiveness and outcomes of annual Pap tests with biennial PPS. The model includes direct costs of screening, diagnostic testing, and treatment for squamous intraepitheial lesions and invasive cancers; indirect costs (eg, lost productivity because of cervical cancer); and newer management practices, including human papillomavirus DNA testing. PATIENTS: Women aged 18 to 64 years. INTERVENTION: Screening for cervical neoplasms with either annual Pap smear test or biennial PPS. MAIN OUTCOME MEASURE: Marginal cost per life-year gained. RESULTS: The probability of women having squamous intraepithelial lesions, cervical cancer, or death from cervical cancer was lower among women undergoing PPS biennially. A total of 12 additional days of life per woman was gained with biennial PPS during the 47-year model period. Total average cumulative direct medical costs per patient were $1419 for biennial PPS compared with $1489 for annual Pap tests. Total costs, including direct medical costs and indirect costs, were $2185 for PPS compared with $3179 for Pap tests alone. Increased savings and patient outcomes were observed in high-risk populations. CONCLUSION: Our simulations indicate that biennial screening with PPS is expected to provide cost savings for women older than 18 years compared with annual Pap test screening, especially for those in high-risk populations.

Collection devices for human papillomavirus.

BACKGROUND: Human papillomavirus (HPV) testing has relied to date on samples collected by experienced health professionals. Self-administered testing devices could allow HPV testing to occur in large-scale epidemiologic studies of primary care screening populations. The purpose of this study is to determine whether a self-collection device for cervicovaginal HPV infection could be developed. METHODS: A prospective randomized trial of a consecutive sampling of 93 women, 18 years or older, receiving routine cervical cancer screening and colposcopy in the urban gynecologic clinics in Philadelphia, Pennsylvania, were randomized into 2 arms. Women in arm 1 used a self-administered tampon before the physician-directed swabs of the cervix; in arm 2, women underwent the physician-directed swab testing before using the self-administered tampon. The concordance of HPV DNA positivity between sampling methods detected by a Hybrid Capture HPV tube test for both low- and high-risk types of HPV was the main outcome measure. RESULTS: The concordance rate (ie, women whose cultures were classified as negative on both tests or positive on both tests) for arms 1 and 2 were similar: 78.3% and 80.9%, respectively. CONCLUSIONS: The tampon was equivalent to the physician-directed swab in HPV detection and suggests its feasibility in long-term primary care studies of screening populations.

The benefits of group music at the 1996 music weekend for women with cancer.

BACKGROUND: Music therapy has been proven to benefit cancer patients physically and emotionally. The Music Weekend for Women with Cancer was developed as a novel opportunity for participants to experience the healing powers of music amidst others who had a shared understanding of their illness. MATERIALS AND METHODS: Fourteen female mixed cancer patients, three spouses, and one daughter attended the weekend from Friday evening through Sunday afternoon. Workshops and events centered on the use of music as a vehicle for expression of emotions, reflection, relaxation, communication, and enjoyment. Questionnaires were collected before the weekend to describe our population as well as three months after the weekend to assess any changes in their utilization of music and mood state. RESULTS: Although insufficiency of post-weekend data limited the potential for assessing the effects of the weekend on the participants' utilization of music and mood state, the extremely positive evaluations supported the role music can play in helping patients and families explore their reactions to cancer. CONCLUSIONS: Events such as this answer the call in the literature for more opportunities to use music and the arts in cancer education. The authors hope this weekend will serve as a prototype for future events that aim to offer the benefits of music.

Is it cost-effective to use a mucosal or paracervical block to relieve the pain and cramping from cryosurgery? A decision model.

BACKGROUND: Cryosurgery is an effective treatment for cervical intraepithelial neoplasia, but it often causes pain and cramping. Both paracervical and mucosal blocks have been shown to provide relief from the pain and cramping associated with cryosurgery. The purpose of this article is to recommend the use of mucosal block, paracervical block, or no block on the basis of which procedure minimizes the costs of averting the pain and cramping that a woman experiences during cryosurgery. METHODS: A decision model was constructed encompassing the options (mucosal block, paracervical block, or no block) that a physician has when performing cryosurgery. The 4 possible outcomes for a patient undergoing cryosurgery were diagrammed as: (1) no pain and no cramping; (2) only cramping; (3) only pain; and (4) both pain and cramping. Each of these outcomes was measured on a 200-mm horizontal visual analog scale. Costs were derived for cryosurgery from the office perspective. Sensitivity analyses were conducted to test the robustness of the analysis. RESULTS: The base case analysis showed that the lowest cost per pain and cramping averted was for women who had a mucosal block before cryosurgery ($153.87), compared with women with a paracervical block ($183.24) and women with no block ($218.83). CONCLUSIONS: A mucosal block is the most cost-effective method to avert the pain and cramping from cryosurgery in women who have taken a nonsteroidal anti-inflammatory drug before the procedure.

Home study course: autumn 1999.

OBJECTIVES: The Home Study Course is intended for the practicing colposcopist or practitioner or practitioner who is seeking to develop or enhance his or her colposcopic skills. The goal of the course is to present colposcopic cases that are unusual or instructive in terms of apperance, presentation, or management, or that demonstrate new and important knowldge in the area of colposcopy or pathology. Participants may benefit from reading and studing the material or from testing thier 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 for physicians. The ASCCP designates this continuing medical education activity for 1 credit hour in Category I of 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.

Cervical mucosal block effectively reduces the pain and cramping from cryosurgery.

BACKGROUND: Cryosurgery is an effective treatment for squamous intraepithelial lesions, but causes pain and cramping regardless of the particular method of cryosurgery used. The purpose of our study was to determine how effective a four-quadrant cervical mucosal block is in reducing the pain and cramping of cryosurgery. METHODS: Of the 112 women presenting for cryosurgery at the teaching clinics of the University of Missouri-Kansas City School of Medicine at Truman Medical Center-East between September 1995 and September 1996, 87 completed the study. The first 39 women were given the standard treatment of no block with the cryosurgery procedure. The subsequent 48 women were given a four-quadrant submucosal block of 1% lidocaine with 1:100,000 epinephrine 5 minutes before cryosurgery. The intensity of pain and cramping of each part of the procedure was measured on 100-mm visual analog scales. RESULTS: The pain and cramping of cryosurgery were significantly reduced (P < .05) with the mucosal block for all measured parts of the cryosurgery procedure, including pain of the first freeze (39 mm vs 12 mm), cramping of the first freeze (49 mm vs 13 mm), pain of the second freeze (24 mm vs 12 mm), cramping of the second freeze (32 mm vs 18 mm), pain of the total composite procedure (44 mm vs 28 mm), and cramping of the total composite procedure (51 mm vs 21 mm). CONCLUSIONS: A four-quadrant mucosal block effectively reduces the amount of pain and cramping associated with cryosurgery.

Increased rates of CD4(+) and CD8(+) T lymphocyte turnover in simian immunodeficiency virus-infected macaques.

Defining the rate at which T cells turn over has important implications for our understanding of T lymphocyte homeostasis and AIDS pathogenesis, yet little information on T cell turnover is available. We used the nucleoside analogue bromodeoxyuridine (BrdUrd) in combination with five-color flow cytometric analysis to evaluate T lymphocyte turnover rates in normal and simian immunodeficiency virus (SIV)-infected rhesus macaques. T cells in normal animals turned over at relatively rapid rates, with memory cells turning over more quickly than naive cells. In SIV-infected animals, the labeling and elimination rates of both CD4(+) and CD8(+) BrdUrd-labeled cells were increased by 2- to 3-fold as compared with normal controls. In normal and SIV-infected animals, the rates of CD4(+) T cell BrdUrd-labeling and decay were closely correlated with those of CD8(+) T cells. The elimination rate of BrdUrd-labeled cells was accelerated in both naive and memory T lymphocytes in SIV-infected animals. Our results provide direct evidence for increased rates of both CD4(+) and CD8(+) T cell turnover in AIDS virus infection and have important implications for our understanding of T cell homeostasis and the mechanisms responsible for CD4(+) T cell depletion in AIDS.

Colposcopy Quality Control: Establishing Colposcopy Criterion Standards for the National Cancer Institute ALTS Trial Using Cervigrams.

OBJECTIVES: The colposcopy quality control (QC) group of the Atypical Squamous Cells of Undetermined Significance-Low-Grade Squamous Intraepithelial Lesions (ASCUS/ LSIL) Triage Study (ALTS) monitors colposcopists at four clinical centers by direct observation and indirectly by assessment of digitized computer colposcopic images transferred nightly by modem. The purpose of this preclinical study was to determine the agreement among colposcopy QC monitors' colposcopic impressions and biopsy site placement through evaluation of cervical photographic images. MATERIALS AND METHODS: A nonparticipant selected 100 Cervigram slides representing four pathologically confirmed categories: cervical intraepihelial neoplasia 1(CIN), CIN2 and CIN3, normal, and cancer. our colposcopy QC monitors and two certified Cervigram evaluators independently interpreted the images for colpocopic impression on two separate occasions. Measures of agreement were calculated for intraobserver, pairwise interobserver, and observer versus histological diagnoses. Participants also indicated the most severe biopsy site by marking an χ on a 4 × 6-inch color print duplication. Mean distances between biopsy site annotations for each pair of evaluators were calculated. RESULTS: The ALTS observer agreement with histology ranged from 75.3% (K = .66) to 47.4% (K = .36) for the first evaluation and 71.1 % (K = .63) to 50.5% (K = .38) for the second evaluation. ALTS interobserver agreement varied between 71 % and 57% for the first interpretation and 76% and I2% for the second evaluation. ALTS intraobserver agreement varied from 86% (K = .86) to 68.0% (K = .60). The mean listances between biopsy site annotations for each pair of ALTS observers varied from 0.99 ± 0.93 mm to 1.44 ± 1.19 nm. CONCLUSIONS: The ALTS colposcopy QC monitors achieved poor to good observer agreement with histology, fair to excellent interobserver agreement, and good to excellent intraobserver agreement in assessing the severity of cervical images. These levels of agreement are similar to many reported by pathologists for cervical cytology and histology interpretations. Monitors also demonstrated a very narrow variation of distance (< 2 mm) for ideal biopsy site placement.