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Biomedical subjects

Attila Lorincz

Publications and source records attributed to Attila Lorincz.

At least 19 recordsLinked to original sources

Visual inspection as a cervical cancer screening method in a primary health care setting in Africa.

We evaluated the feasibility and performance of visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) for cervical cancer screening in a primary health-care setting in Kinshasa, Congo. Women (1,528) aged > or =30 years were screened independently by nurses and physicians by VIA and VILI and Pap cytology. Biopsy samples were obtained from women with abnormal colposcopies and from 290 randomly chosen women with normal colposcopy. Cytological and histological examinations were performed in Lyon and Montreal, respectively. The prevalence of cervical intraepithelial neoplasia (CIN) of grades 1, 2 and 3 was 4.5, 1.3 and 4%, respectively. Using biopsy as the reference, the sensitivity, specificity and negative predictive value (NPV) for > or =CIN 2 for VIA-nurse were 55.5% (95% CI: 34.7-76.2), 64.6% (95% CI: 62.0-67.1) and 96.8% (95% CI: 93.5-98.7), respectively. The corresponding values for VILI-nurse were 44.0% (95% CI: 24.2-63.8), 74.6% (95% CI: 72.3-76.9) and 96.7% (95% CI: 93.7-98.6). The equivalent parameters for physicians were 71.1% (95% CI: 46.7-95.5), 71.3% (95% CI: 68.9-73.6) and 98.6% (95% CI: 96.0-99.7) for VIA and 68.3% (95% CI: 42.5-94.0), 76.2% (95% CI: 74.0-78.4) and 97.2% (95% CI: 95.3-98.5) for VILI. The sensitivity of cytology ranged between 31 and 72%, depending on the abnormality threshold used to define positivity, with a corresponding specificity range of 94-99% and a NPV range of 97-99%. Our results show that VIA and VILI performed by nurses and physicians are slightly more sensitive but less specific than Pap cytology across multiple combinations of test and lesion thresholds. Given their lower cost and easy deployment, visual inspection methods merit further assessment as cervical cancer screening methods for low-resource countries.

Acetic Acid↗

Universal Collection Medium (UCM) is as suitable as the Standard Transport Medium (STM) for Hybrid Capture II (HC-2) assay.

BACKGROUND: Collection of cervical-vaginal material in liquid media enables simultaneous evaluation of both oncologic cytology and molecular tests for the detection of Human papillomavirus (HPV), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). Universal Collection Medium (UCM) has been developed to fulfill this objective. OBJECTIVES: To compare Hybrid Capture II (HC-2) to diagnose HPV, NG and CT in specimens collected in UCM and in the current Digene Standard Transport Medium (STM). STUDY DESIGN: The study was cross-sectional. Three collections of endocervical and ectocervical material were performed in each of 893 women referred for colposcopy in the following order: (1) to prepare a conventional Pap smear slide using the accompanying brush of the STM kit and with Ayre spatula; (2) for HC-2 test and liquid-based cytology using a 1 ml UCM vial as transport medium; material was collected with another similar brush; (3) for HC-2 test using a 1 ml STM vial as transport medium; material was collected with the same brush that we used in the procedure no. (1) (conventional Pap smear). HC-2 results from samples taken from STM and UCM media were compared by using simple linear regression analysis and Kappa statistic. RESULTS AND CONCLUSIONS: HC-2 results from the two media were highly correlated: high-risk HPV (kappa=0.92; r(2)=0.92), low-risk HPV (kappa=0.85; r(2)=0.86) and NG/CT (kappa=0.96; r(2)=0.81). Despite being obtained from a second specimen, the UCM HC-2 results were equivalent to those obtained with the standard medium STM and the UCM medium.

Adolescent↗

Totally minimally invasive robot-assisted unstented pyeloplasty using the Zeus Microwrist Surgical System: an animal study.

BACKGROUND: Minimally invasive pyeloplasty is a difficult procedure even for an expert laparoscopic surgeon. The major difficulty is associated with the limitations of intracorporeal suturing and knot tying. Surgical robots, which hold minimally invasive surgical instruments, have wrists and provide tremor filtration and motion scaling that might be expected to facilitate complex procedures in newborns. METHODS: Seven survival piglets (4.0-7.5 kg) underwent a totally minimally invasive robot-assisted unstented pyeloplasty employing the Zeus Robotic Microwrist System. The ureter was transected at the level of the ureteropelvic junction and 8 mm was resected. The unstented anastomosis was fashioned with running suture and intracorporeal knot tying. The animals were recovered and intravenous urography was performed at 1 month. After sacrifice, the anastomosis and the kidney were evaluated grossly and histologically for leak, caliber, and healing. RESULTS: All animals survived the procedure without postoperative complications. The mean robotic setup time was 19 minutes (range, 10-30 min), mean anastomosis time 51 minutes (range, 39-63 min), and mean total operation time 76 minutes (range, 57-87 min). The urography showed hydronephrosis in the first animal. The other 6 animals had no abnormalities. Histopathology demonstrated severe hydronephrosis in the first pig and moderate hydronephrosis in the sixth and seventh. All other animals had no sign of hydronephrosis. All anastomoses were well healed and intact. CONCLUSIONS: Robot-assisted laparoscopic pyeloplasty is a technically feasible procedure with acceptable morbidity in an animal model. The robotic technology enhances surgical dexterity and precision. Robotic assistance can increase the applicability of minimally invasive surgery to complex procedures in children.

Anastomosis, Surgical↗

Computer-assisted, robot-enhanced open microsurgery in an animal model.

BACKGROUND: Computer-assisted, robot-enhanced surgery improves laparoscopic and thoracoscopic surgery through tremor filtration, motion scaling, articulation, and improved ergonomics. Surgeons perform many open cases under magnification that magnifies the tremor present in all surgeons' hands, so the tremor filtration and motion scaling of robotic surgery may improve microsurgery. Our goal was to compare microvascular anastomoses performed with a robot-enhanced technique with a standard technique. METHODS: We performed end-to-end anastomoses in 1-mm rat femoral arteries with interrupted 10-0 suture. We compared the anastomotic time, patency, and leak rates between traditional microsurgery techniques (by hand) and a robot-enhanced technique using the Zeus robotic surgery system (Computer Motion, Goleta, California). The surgeon used an operative microscope for visualization in both techniques. RESULTS: We performed 30 anastomoses by hand and 31 with Zeus. We observed a remarkable degree of tremor filtration in the robot-enhanced cases. Anastomotic times for both techniques demonstrated a learning curve. Anastomoses done by hand (mean time, 17.2 minutes) were significantly faster than those done with Zeus (mean time, 27.6 minutes) (P = 0.0006). All anastomoses from both groups were patent, and none leaked after 3 minutes. CONCLUSION: The Zeus system is effective at performing complex, open, microsurgery tasks in vivo. There was no measurable benefit from the remarkable tremor filtration and motion scaling offered by robot-enhanced surgery.

Anastomosis, Surgical↗

Laparoscopic Morgagni hernia repair in children using robotic instruments.

BACKGROUND: Robotic surgery enhances minimally invasive surgery through tremor filtration, motion scaling, indexed movement, articulation, and improved ergonomics. We report 2 cases of computer- assisted, robot-enhanced, laparoscopic repair of Morgagni hernia in a 23-month-old weighing 10.2 kg and a 5-year-old weighing 21.6 kg. METHODS: Four 5 mm trocars were used to gain access to the abdomen. In the first case, standard laparoscopic instruments were used to dissect the liver from the rim of the defect and then reduce the hernia. In the second, robotic instruments were used for this dissection. In both cases, the robot- enhanced instruments were used to close the hernia defects with interrupted, nonabsorbable suture, using intracorporeal knot tying. RESULTS: Both cases were completed laparoscopically without a patch. The robotic system took 9 minutes to set up and drape. The average operative time was 227 minutes. The older child tolerated oral intake the day of surgery and went home the following day. The younger child tolerated oral intake and went home on postoperative day 2. CONCLUSION: Robot-assisted laparoscopic Morgagni hernia repair is feasible.

Child, Preschool↗

High-risk human papillomavirus detection and related risk factors among pregnant and nonpregnant women in Mexico.

BACKGROUND: Significant differences in human papillomavirus (HPV) prevalence between pregnant and nonpregnant women have been reported. Some studies suggest that physiological processes during pregnancy modify the host-immune response, increasing detectability of high-risk HPV infection as a result of viral reactivation. It remains uncertain, however, whether pregnancy has an effect on HPV DNA positivity as a result of a general lack of data and based on contradictory results found in previous epidemiologic studies. We conducted an epidemiologic study to identify differences in the prevalence of HPV infection between pregnant and nonpregnant women in Mexico. We also investigated the relationship of HPV DNA positivity with socioeconomic, gynecologic, and obstetric risk factors. METHODOLOGY: We screened pregnant and age-matched nonpregnant women for high-risk HPV infection. The study population was clients of the family medicine healthcare services of the Mexican Institute of Social Security in Cuernavaca, Morelos, Mexico. A total of 274 pregnant and 1060 nonpregnant study participants were screened for the presence of high-risk HPV DNA in self-collected specimens by the Hybrid Capture 2 test (HC2; Digene Corp., Gaithersburg, MD). RESULTS: High-risk HPV DNA was detected in 37.2% (95% confidence interval [CI], 31-43%) of pregnant women and in 14.2% (95% CI, 12-16%) of nonpregnant women. Combining both groups for the multivariate analysis, pregnancy was associated with an increased risk for HPV infection (odds ratio, 3.5; CI, 2.7-4.9). CONCLUSIONS: Our results are consistent with other studies reporting increased high-risk HPV detection rates among pregnant women. HPV-positive status in pregnant and nonpregnant women appears to be influenced by age. The decrease in HPV positivity by number of pregnancies in both currently pregnant and nonpregnant women is consistent with a possible effect of immune protection as a result of earlier HPV infections. Despite lack of information about a woman's history of sexual behavior, these data support the hypothesis that an alteration of immunologic responses during pregnancy may be associated with an increased risk of HPV acquisition or reactivation.

Adolescent↗

Cervical biopsy-based comparison of a new liquid-based thin-layer preparation with conventional Pap smears.

The objective of this study is to compare the diagnostic efficacy of universal collection medium (UCM) liquid-based cytology (LBC) (Digene Corp., MD) and the conventional Pap smear in a comparative study, using histologic results as the gold standard. This was a cross-sectional study. Conventional Pap smears and UCM LBC specimens, obtained from women in a low socioeconomic outpatient population referred to a tertiary center for gynecologic care, were compared. For the purpose of this study, when cervical specimens were collected for cytology, all women underwent colposcopy and biopsy was done if a cervical abnormality was observed. Cytologic evaluation of UCM LBC and conventional Pap smears were carried out separately, masked to the results of the other method. Agreement beyond chance between the two cytologic methods was ascertained by means of the unweighted kappa statistic. Sensitivity, specificity, and predictive values with 95% confidence intervals were calculated for both methods. McNemar's test was used to determine the level of association between the two cytology procedures. A total of 800 women were evaluated. Assessment of the overall agreement between the two cytologic methods yielded a kappa of 0.777 (P < 0.0001). After adjustment for histologic diagnosis, the computed kappa in each stratum was as follows: normal = 0.733; CIN 1 = 0.631; CIN 2/3 = 0.735; cancer = 0.652. The sensitivity and specificity of UCM LBC for detection of cervical intraepithelial lesions and cancer were 75.3% and 86.4%, respectively, not statistically different from the 81.8% and 85.2% seen with the conventional method. This study demonstrates that the UCM LBC method is as accurate as the conventional Pap smear cytology in detecting cervical intraepithelial lesions and cancer even so the UCM samples were systematically prepared from a second sampling of the cervix.

Biopsy↗

Computer-assisted robot-enhanced laparoscopic fundoplication in children.

BACKGROUND/PURPOSE: Robotic surgery improves laparoscopic surgery through a more natural interface, tremor filtration, motion scaling, and additional degrees of freedom of the instruments. Here, the authors report that experience with robot-assisted fundoplication in children. METHODS: The authors have performed 15 laparoscopic fundoplications with the Zeus Robotic Surgery System and retrospectively reviewed prospectively collected data on set-up time, operating time, and outcome. RESULTS: All cases were completed successfully: one Heller myotomy with Dor fundoplication and 14 Nissen fundoplications. Patients ranged from 2 months to 18 years old (mean, 4.3 years) and from 3.4 kg to 37.7 kg (mean, 13.0 kg). There were no technical errors, equipment errors, or conversions. There were no complications in the first 30 days after surgery. The operating time declined from 323 minutes for the first case to 180 minutes for the last (mean, 195 minutes). The 14th case was the shortest at 123 minutes. Setting up the robotic surgery system took an average of 11 minutes. The surgeons perceived benefits of greater ease and confidence in suture placement and knot tying. CONCLUSIONS: The authors have successfully used surgical robots for gastric fundoplication at a pediatric teaching hospital. Our experience with this operation has shown the additional dexterity that the robot provides and will pave the way to more complex procedures.

Adolescent↗

Raman spectroscopy for neoplastic tissue differentiation: a pilot study.

BACKGROUND: Several changes occur during the transformation of normal tissue to neoplastic tissue. Such changes in molecular composition can be detected by Raman spectroscopy. Raman spectroscopy is a nondestructive method of measuring these changes, which suggests the possibility of real-time diagnosis during medical procedures. METHODS: This study seeks to evaluate the ability of Raman spectra to distinguish tissues. The Raman signatures of normal kidney, lung, and liver tissue samples from pigs and rats were characterized in vitro. Further, a human neuroblastoma and a hepatoblastoma, obtained at resection were also studied. RESULTS: The Raman spectra of the animal samples of kidney, liver, and lung are distinctly different in the intensity distribution of the Raman peaks. Further, the spectra of a given organ from pigs and rats, although similar, were different enough to distinguish between the 2 animals. In the patient tissues, the Raman spectra of normal liver, viable tumor, and fibrotic hepatoblastoma were very different. Fibrotic tissue showed a greater concentration of carotenoids, whereas viable tissue was rich in proteins and nucleic acids. The normal tissue showed both components. Similar differences were also seen in the neuroblastoma tissue. CONCLUSIONS: The results of this study show the potential use of Raman spectroscopy in clinical diagnosis.

Animals↗

Robotically assisted esophago-esophagostomy in newborn pigs.

PURPOSE: Repair of esophageal atresia and tracheoesophageal fistula (TEF) in the newborn is challenging when done as an open procedure but only a few surgeons have attempted this with minimally invasive surgery (MIS). Surgical robots that hold MIS instruments have wrists and provide tremor filtration and motion scaling, which might be expected to facilitate complex procedures in small spaces such as an esophageal anastomosis in a newborn. METHODS: Seven newborn pigs weighing 2 to 3 kg were used as a model. The authors performed an esophageal resection and end-to-end anastomosis using the Zeus Microwrist Robotic Surgical System. The authors monitored the following data-Zeus robotic set-up time, operating time, esophageal dissection time, and anastomosis time. After 1 month, the animals were anesthetized to perform esophagram and than were killed. RESULTS: In these very small animals the space available for performing an anastomosis is very limited, approximately 2 cm3. Two pigs each died 18 days postoperatively. One animal could not eat and died during esophageal dilation. The second pig died of unrelated enteritis. Neither had evidence of anastomotic leak at autopsy. The esophagram of the 5 pigs that survived for 30 days showed no narrowing or proximal dilation in 2. In 3 there was some stenosis requiring dilation. Histopathology was done on each operated animal. Two of the anastomoses were well healed, and 5 showed only focal small ulceration. CONCLUSIONS: Robotic assistance facilitates an MIS approach to the upper esophagus even in the limited space of the infant chest.

Anastomosis, Surgical↗

Robot-enhanced fetoscopic surgery.

BACKGROUND: Fetoscopic surgery carries with it less maternal morbidity than open fetal surgery. Robotic surgery facilitates endoscopic surgery through tremor filtration, motion scaling, indexed movement, articulation, and improved ergonomics. The goal of the authors was to explore using a robotic surgery platform in a fetal animal model. METHODS: Using the Zeus Robotic Surgery System (Computer Motion, Santa Barbara, CA), fetoscopic surgery in pregnant sheep was performed using a variety of techniques: uterus exteriorized or totally percutaneous and with liquid or gas insufflation. Using the percutaneous technique and gas insufflation, the authors created and sutured fetal skin and fascial defects. The ewes were recovered and killed 2 weeks postoperatively, and autopsies were performed on them and their fetuses. RESULTS: In the exteriorized uterus model, instrument movement was unpredictable and fluid leaked. In the fluid environment, clouding of the visual field and difficulty in immobilizing the fetus were major difficulties. In the survival model, 4 of the 6 fetuses survived to autopsy at 2 weeks and showed good healing grossly and histologically. CONCLUSIONS: The Zeus Robotic Surgery System can be used for fetoscopic surgery in a sheep model. The percutaneous approach with a nitrous oxide environment is the most effective. Advantages of robotic surgery may be applicable in fetoscopic surgery, but further work in a primate model is required.

Animals↗

Optimal cutoff of the hybrid capture II human papillomavirus test for self-collected vaginal, vulvar, and urine specimens in a colposcopy referral population.

OBJECTIVE: To estimate the optimal relative light unit ratio, as a measure of viral load, of the Hybrid Capture II human papillomavirus (HPV) test in self-collected specimens for detecting cervical intraepithelial neoplasia (CIN). METHODS: Two hundred women referred for colposcopy with abnormal cytologic, self-collected vaginal and vulvar swabs and urine for HPV testing. The receiver operating characteristic (ROC) curve method was used to estimate optimal cutoffs for the Hybrid Capture II test. The reference standard was colposcopy, with directed biopsy as required. RESULTS: The estimated optimal cutoffs of the relative light unit ratio for detecting CIN 2 or higher for urine, vulvar, and vaginal samples gave sensitivities of 72.4%, 82.8%, and 89.0% and specificities of 57.0%, 52.1%, and 55.9%, respectively. At the manufacturer's recommended 1.0 cutoff, sensitivities were 44.8%, 62.1%, and 86.2% for urine, vulvar, and vaginal samples, with specificities of 69.7%, 62.7%, and 53.5%, respectively. The likelihood ratios (likelihood of being truly positive after a positive test result) were similar for the optimal and the 1.0 cutoff. CONCLUSIONS: The ROC curve methods did not improve the overall diagnostic accuracy of the Hybrid Capture II test compared with the 1.0 relative light unit ratio cutoff.

Journal Article↗

Digene Corporation.

Digene Corporation is a molecular diagnostics company that develops, manufactures and markets proprietary gene-based testing systems for the screening, monitoring and diagnosis of human diseases. The company's primary focus is in women's cancers and infectious diseases. Our proprietary, patented Hybrid Capture((R)) technology has been successfully applied to the development of diagnostic tests for human papillomavirus (HPV), Chlamydia, Gonorrhea, hepatitis B virus and cytomegalovirus. Digene's Hybrid Capture 2 (hc2) trade mark HPV DNA test has now been established as part of the standard of care for cervical cancer screening in the US. We are focusing our research and development activities on support and improvement of existing product lines as well as the development of several new products. We have several ongoing basic research programs with the goal of developing improved molecular diagnostic assay systems for the detection of HPV and other targets of interest in the area of women's cancers and infectious diseases. Digene's goal is to establish primary screening by the Hybrid Capture HPV DNA Test as the worldwide standard of care for cervical cancer screening.

DNA↗

Incidence, clearance and predictors of human papillomavirus infection in women.

BACKGROUND: Persistent infection with carcinogenic human papillomavirus (HPV) is linked to high-grade lesions and cervical cancer. To better understand the natural history of HPV, we sought to determine the rates of incident and cleared carcinogenic HPV infection, by age, among women aged 15-49 years and to explore risk factors for incident infection. METHODS: Women enrolled in an earlier HPV prevalence survey (500 of 800 who were HPV-negative and all 121 who were HPV-positive) were invited to participate in follow-up HPV testing at their periodic health examination one year later. A cervical soft-brush specimen for HPV testing and a smear for cytologic examination were obtained, and participants completed a questionnaire on their demographic characteristics and sexual history. RESULTS: Two hundred and fifty-three (50.6%) previously HPV-negative women and 54 (44.6%) previously HPV-positive women were retested. The mean interval between visits was 14.0 (standard deviation 2.0, median 13.5, range 9.0-21.3) months. Incident HPV infection occurred in 11.1% (28/253) of the women overall, with the highest rate, 25.0% (6/24), in the 15-19-year age group. In the univariate analyses, risk factors for incident HPV were the median number of sexual partners in the past year (< or = 1 v. > or = 2: odds ratio [OR] 8.2, 95% confidence interval [CI] 3.0-22.2; p < 0.001) and the median number of sexual partners over a lifetime (> 3 v. < or = 3: OR 3.0, 95% CI 1.2-7.2; p = 0.014). In multivariate logistic regression modelling adjusted for age, median number of sexual partners in the past year, median number of sexual partners over a lifetime, marital status, current smoking and current use of oral contraceptives, only the median number of sexual partners in the past year remained significantly associated with incidence (OR 6.2, 95% CI 1.6-24.5; p = 0.009). Of the previously HPV-positive women, 51.9% (28/54) had cleared the infection. INTERPRETATION: Incident infection with carcinogenic HPV was highest in women aged 15-19 years, and risk factors were consistent with a sexually transmitted infection. A large proportion of the women who were HPV-positive appeared to have cleared the infection after one year.

Adolescent↗

Comparison of HPV-based assays with Papanicolaou smears for cervical cancer screening in Morelos State, Mexico.

OBJECTIVE: To compare the performance of human papillomavirus (HPV) assays with conventional Pap cytology for cervical cancer (CC) screening in Mexico. METHODS: Pap smears, self-collected vaginal specimens (SS) for HPV testing, and clinician-collected cervical specimens (CS) for HPV testing were obtained from 7868 women, aged 15-85 years old, attending CC screening at the Mexican Institute of Social Security (IMSS) between May and October, 1999. SS and CS specimens were screened for oncogenic HPV DNA by Hybrid Capture 2. Women who received cytological interpretations of atypical squamous cells of undetermined significance (ASCUS), and/or a positive HPV test were referred for colposcopy and histologic studies. The relative estimates for sensitivity, specificity and predictive values of each test were calculated using histological diagnoses of cervical intraepithelial neoplasia (CIN) grades 2 or 3, or CC histological diagnosis. RESULTS: Oncogenic HPV detection rate was 11.6% for SS, and 9.3% for CS. Pap smear abnormalities were observed in 2.4% of the women. Of 1147 women who had at least one abnormal test result, 88.5% underwent colposcopy, and 101 biopsy-confirmed CIN2/3 or cancer cases were identified. The relative sensitivity estimates for the Pap test, SS and CS were 59.4% (95% CI: 49.2-68.9), 71.3% (95% CI: 61.3-79.6), and 93.1% (95% CI: 85.8-96.9), respectively, while the specificities were 98.3% (95% CI: 98.0-98.6), 89.2% (95% CI: 88.5-89.9), and 91.8% (95% CI: 91.2-92.4), respectively. The positive predictive values of Pap, SS and CS were 36.1, 9.1 and 14.9, the colposcopy referrals needed to detect a case of CIN2/3 or cancer were 2.8, 11.0 and 6.7, respectively. DISCUSSION: Both HPV assays detected more cases of CIN2/3 or CC than Pap cytology alone. However, the HPV assays increased the number of colposcopy referrals. Our study suggests that HPV testing could be an effective way to improve the performance of CC screening.

Adolescent↗

Robotics and the pediatric surgeon.

Surgical robots are enabling devices for minimally invasive (laparoscopic) surgery (MIS). They use a computer to enhance a surgeon's skills as hand movements are transmitted to robotic arms. The computer filters tremor, which becomes important at high magnifications of 10 to 15 times available in MIS. It also provides motion scaling so that large hand movements are converted to very small movements of the robotic arm. The robotic arms also have wrists that make suturing and knot tying far more accurate and efficient. Surgical robots are currently used clinically for procedures such as MIS Nissen fundoplication, cholecystectomy, and splenectomy. Laboratory experience indicates that they may provide advantages for newborn procedures such as portoenterostomy for biliary atresia and repair of esophageal atresia and tracheoesophageal fistula. They have a potential for making possible MIS procedures, which can only be done open now, and for introducing entirely new procedures as well as for the performance of procedures by operators distant from the patient.

Age Factors↗

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↗

A comparison between real-time polymerase chain reaction and hybrid capture 2 for human papillomavirus DNA quantitation.

Studies investigating human papillomavirus (HPV) viral load as a risk factor in the development of squamous intraepithelial lesions (SILs) and cancer have often yielded conflicting results. These studies used a variety of HPV viral quantitation assays [including the commercially available hybrid capture 2 (HC 2) assay], which differ in their ability to account for differences in cervical cell collection, linear dynamic range of viral load quantitation, and determination of type-specific versus cumulative viral load measures. HPV-16 and HPV-18 viral quantitation using real-time PCR assays were performed to determine whether type-specific viral load measurements that adjust for specimen cellularity result in a different association between viral load and prevalent SIL and cancer, compared with HC 2 quantitation (which does not adjust for cellularity or multiple infections). In general, HPV-16 viral load as measured by real-time PCR increased linearly with increasing grade of SIL while HPV-18 measured using similar techniques increased through low-grade SIL (LSIL), with HPV-18 viral load among high-grade SIL and cancers near the level of cytologically normal women. HC 2 viral load, using the clinical 1.0 pg/ml cut point, differentiated cytologically normal women from women with any level of cytological abnormality (normal versus >/=LSIL) but did not change as lesion severity increased. There was no evidence for plateau of HC 2 at high copy numbers, nor was significant variability in total specimen cellularity observed. However, cumulative viral load measurements by HC 2, in the presence of multiple coinfections, overestimated type-specific viral load. Multiple infections were more common among women with no (32%) or LSIL (51%) [versus 23% in high-grade SIL/cancer], partially explaining the lack of a dose response using a cumulative HC2 viral load measure. The nonrandom distribution of multiple infections by case-control status and the apparent differential effect of viral load by genotype warrant caution when using HC 2 measurements to infer viral load associations with SIL and cancer.

Carcinoma, Squamous Cell↗