Application an internet facilitation in a community-based cervical cancer screening project.

OBJECTIVE: To evaluate the feasibility of an internet-facilitated community model for cervical cancer screening using self-collected HPV testing as primary screening. METHOD: A population-based cervical cancer screening program was conducted in the suburb of Shenzhen, China, from September 2014 to July 2017. Women with 25-60 years of age and no pregnancy were eligible for participation. Participants could register for screening by logging in a website by themselves or with the aids of local community workers. A unique barcode was issued to each applicant upon successful registration. After registration, women could get sampling kits from community screening site/study clinic, collect vaginal samples privately or in group, and provide their sample for Hr-HPV tests on Cobas4800 and SeqHPV assays. Testing reports were checkable through personal account for all participant and phone calls were given to all women positive of Hr-HPV. Participants positive of both or either the 2 assays were identified as the positives. The positives could return the study clinic for triage or search medical care in other clinics. Colposcopy directed or ramdom biopsies were performed on all positives who returned to the study clinics. RESULTS: A total of 10,792 community women registered for screening, among whom, 10,010 provided their vaginal samples for tests. 99.5% of the participants were confirmed to have correct personal identifiable information and samples, and 98.9% of them got HPV testing results from both or either assays. No adverse event was reported. CONCLUSION: When self-collected HPV testing is used as the primary testing, the internet-based data platform facilitates the screening in registration, data collection, and data tracking, and increases the screening coverage. Internet-facilitated community model is promising to cervical cancer control and applicable in regions with variety of resources.

Comparison of cycle threshold values of the Cobas HPV test and viral loads of the BMRT HPV test in cervical cancer screening.

Objective: To validate the HPV viral loads that are reflected by the cycle threshold values of Cobas4800 as the viral load indicators by verifying the consistency of the viral loads per unit (10,000 cells) from the BMRT assay. Methods: The analysis is based on data from the Chinese Multi-Center Screening Trial (CHIMUST). The cases included in the analysis are all positive for physician-collected hrHPV on SeqHPV and/or Cobas4800 or negative for hrHPV but abnormal in cytology (≥LSIL), and some cases selected by nested case-control randomization from those negative for physician-collected hrHPV and cytology. With HPV testing results and relevant Ct values from Cobas4800 available, we tested the entire sample set with the BMRT HPV testing assay and analyzed their agreement with Cobas4800, followed by a comparison of the CtV from Cobas4800 and viral loads (lg) from BMRT by lesion grade. Results: We included 4,485 women (mean age: 45.4 years) in the study, and 4,290 had complete data. The consistency of genotypes from Cobas4800 and BMRT for hrHPV, HPV-16, HPV-18, and 12-HPV pools was 94.9% (4070/4290, Kappa = 0.827), 99.1% (4251/4290, Kappa = 0.842), 99.6% (4,273/4,290, Kappa = 0.777), and 95.3% (4,089/4,290, Kappa = 0.821), respectively. Further analysis shows that any inconsistency between the two assays is likely among samples with comparatively lower viral loads. When analyzing per lesions of CIN2+ and CIN3+, the CtV from Cobas4800 and VL (lg) from BMRT are highly correlated inversely and follow the linear regression for HPV16 and 12-HPV pool (Pearson's or Spearman's correlation coefficient (r): In CIN3+, r HPV16 = -0.641, P < 0.001; r 12-HPVpool = -0.343, P = 0.109; In CIN2+, r HPV16 = -0.754, P < 0.001; r 12-HPVpool = -0.429, P < 0.001). Conclusion: The CtV from Cobas4800 and the viral loads (lg) of per unit cells from the BMRT are well correlated for lesion grading when tested on physician-collected samples. Cobas-CtV is worthy of further study for clinical application.

Prevalence of Human Papillomavirus Among Chinese Han and Mongols Minority Women in Inner Mongolia, China: Reflected by Self-Collected Samples in CHIMUST.

Background: The disparities of hr-HPV infection among races/ethnicities have not been fully discussed. This study aimed to investigate the difference of hr-HPV infection between Chinese Han and Mongols minority women in Inner Mongolia. Methods: Genotyping and histopathology data of Chinese Han and Mongols minority women in Inner Mongolia from Chinese Multi-Center Screening Trial were used to analyze the hr-HPV prevalence, and type-specific distribution in abnormal pathology results. Results: The hr-HPV infection rates of Han women was 15.9% while of Mongols was 21.6% (P < 0.001). The most prevalent genotypes in Han women were ranked as HPV-16,-52,-18/-58,-31/-39, and-59 while in Mongols were-16,-31,-58,-18 and-52. When analyzing the age-specific of hr-HPV infection, two peaks were found at age of 40-44 (20.5%) and 55-59 (23.5%) years in Han women while three peaks were observed at age of 30-34 (22.1%), 45-49 (22.9%), and 55-59 (31.8%) years, respectively, in Mongols. HPV-16 accounting for 62.5 and 53.8% of the CINII+ in Han and Mongols, respectively. Conclusion: The prevalence of hr-HPV was significantly different between the Han and Mongols minority women in Inner Mongolia, races/ethnicities background should be taken into consideration for the refinement of cervical cancer screening strategies and vaccine implementation in China.

[Performance of vaginal self-sampling high-risk HPV genotyping as primary and combining cytology or viral load as secondary in cervical cancer screening].

Objective: To evaluate the efficacy of high-risk HPV (HR-HPV) genotyping with vaginal self-sampling in primary screening and combining cytology or viral load for HR-HPV positive as secondary screening strategies. Methods: The data referring to HR-HPV genotyping of self-collected sample with mass array matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS), HR-HPV viral load of physician-collected sample with hybrid capture Ⅱ (HC-Ⅱ), liquid-based cytology and histology of 8 556 women were from Shenzhen cervical cancer screening trial Ⅱ (SHENCCAST-Ⅱ) conducted between April 2009 and April 2010. The data were reanalyzed to determine the sensitivity and specificity to cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN Ⅱ+), CIN of grade 3 or worse (CIN Ⅲ+) when HR-HPV genotyping combining with colposcopy as primary screening strategy based on varied HR-HPV subtype (strategy 1, including 5 sub-strategies: 1a: HPV 16/18 positive; 1b: HPV 16/18/58 positive; 1c: HPV 16/18/58/31/33 positive; 1d: HPV 16/18/58/31/33/52 positive; 1e: any HR-HPV positive). The data were also compared to determine the efficacy of cytology (strategy 2, including 5 sub-strategies: 2a, 2b, 2c, 2d, 2e) or HR-HPV viral load (strategy 3, including 4 sub-strategies: 3a, 3b, 3c, 3d) of physician-collected sample as a triage with HR-HPV genotyping for self-sampling HR-HPV positives. Results: (1) The HR-HPV positive rate was 13.77% (1 178/8 556) in the self-collected samples of 8 556 pregnant women. Of them,the prevalences of HPV 16/18, HPV 16/18/58, HPV 16/18/58/31/33 and HPV 16/18/58/31/33/52 were 3.16% (270/8 556), 5.14% (440/8 556), 6.66% (570/8 556) and 9.81% (839/8 556), respectively. The HR-HPV viral load ≥10 relative light units/control (RLU/CO) was 8.87%(759/ 8 556), while cytological results ≥atypical squamous cell of undetermined signification (ASCUS) were 12.05% (1 031/8 556). (2) The strategy 1e had the highest sensitivities for CIN Ⅱ+, CIN Ⅲ+ which were 92.70% and 94.33%,respectively,among 14 sub-strategies,while the lowest specificity and positive predictive value (PPV). Meanwhile,the required colposcopy referral rates were much higher than other 13 sub-strategies (13.77%). The other 4 sub-strategies of strategy 1 (1a, 1b, 1c, 1d), strategy 1a had the highest specificities for CIN Ⅱ+ and CIN Ⅲ+ (97.92%, 97.69%, respectively), while 1d had the highest sensitivities for CIN Ⅱ+ and CIN Ⅲ+ (88.41%, 92.20%, respectively). (3) Both strategies of referring self-sampling HPV 16/18 positives for immediate colposcopy followed by triage physician-collected sample cytology (≥ASCUS) or viral load (≥10 RLU/CO) for non-HPV 16/18 positives had significantly higher sensitivity and specificity for CIN Ⅱ, CIN Ⅲ+, as well as lower referral rates (strategy 2a and 3a). Additionally, based on these two secondary screening strategies, cumulatively using the other four HR-HPV (HPV 58, 31, 33 and 52) positives as triage for immediate colposcopy showed an enhanced sensitivity. Conclusions: Primary HR-HPV cervical cancer screening strategy based on self-sampling with triage of cytology (≥ASCUS) or viral load (≥10 RUL/CO) provides a good balance among sensitivity, specificity for CIN Ⅱ+ and CIN Ⅲ+ and the number of tests required, referral rates. The efficacy of HR-HPV genotyping combining cytology or viral load secondary screening strategies will have a spiral escalation when HPV 58, 31, 33, 52 are included.

[Clinical value of p16INK4a immunocytochemistry in cervical cancer screening].

Objective: To evaluate the value of p16INK4a detected by p16INK4a immunostaining as a new generation of cervical cytology for primary screening and secondary screening in population-based cervical cancer screening, and in improving cytological diagnosis. Methods: Between 2016 and 2018, 5 747 non-pregnant women aged 25-65 years with sexual history were recruited and underwent cervical cancer screening via high-risk (HR)-HPV/liquid-based cytological test (LCT) test in Shenzhen and surrounding areas. All slides were immuno-stained using p16INK4a technology, among them, 902 cases were offered p16INK4a detection during primary screening, and the remaining 4 845 cases were called-back by the virtue of abnormal HR-HPV and LCT results for p16INK4a staining. Participants with complete LCT examination, HR-HPV test, p16INK4a staining and histopathological examination results were included in this study. The performance of p16INK4a in primary and secondary screening, and in assisting cytology to detect high grade squamous intraepithelial lesion [HSIL, including cervical intraepithelial neoplasia (CIN) Ⅱ or Ⅲ] or worse [HSIL (CIN Ⅱ)+ or HSIL (CIN Ⅲ)+] were analyzed. Results: (1) One-thousand and ninety-seven cases with complete data of p16INK4a and histology were included. Pathological diagnosis: 995 cases of normal cervix, 37 cases of low grade squamous intraepithelial lesion (LSIL), 64 cases of HSIL and one case of cervical cancer were found. Among them, 65 cases of HSIL (CIN Ⅱ)+ and 34 cases of HSIL (CIN Ⅲ)+ were detected. The positive rate of p16INK4a in HSIL (CIN Ⅱ)+ was higher than that in CINⅠ or normal pathology (89.2% vs 10.2%; P<0.01). (2) p16INK4a as primary screening for HSIL (CIN Ⅱ)+ or HSIL (CIN Ⅲ)+ was equally sensitive to primary HR-HPV screening (89.2% vs 95.4%, 94.1% vs 94.1%; P>0.05), but more specific than HR-HPV screening (89.8% vs 82.5%, 87.7% vs 80.2%; P<0.05). p16INK4a was equally sensitive and similarly specific to cytology (≥LSIL; P>0.05). (3) The specificity of LCT adjunctive p16INK4a for detecting HSIL (CIN Ⅱ)+ or HSIL (CIN Ⅲ)+ were higher than that of LCT alone or adjunctive HR-HPV (P<0.01), while the sensitivity were similar (P>0.05). (4) p16INK4a staining as secondary screening: p16INK4a was significantly more specific (94.1% vs 89.7%, 91.9% vs 87.4%; P<0.01) and comparably sensitive (84.6% vs 90.8%, 88.2% vs 91.2%; P>0.05) to cytology for triaging primary HR-HPV screening. HPV 16/18 to colposcopy and triage other HR-HPV with p16INK4a was equally sensitive (88.2% vs 94.1%; P=0.500) and more specific (88.3% vs 83.0%; P<0.01) than HPV 16/18 to colposcopy and triage other HR-HPV with LCT≥ atypical squamous cells of undetermined significance (ASCUS), and the referral rate decreased (14.0% vs 19.4%; P=0.005). Conclusions: For primary screening, p16INK4a is equally specific to cytology and equally sensitive to HR-HPV screening. p16INK4a alone could be an efficient triage after primary HR-HPV screening. In addition, p16INK4a immunostaining could be used as an ancillary tool to cervical cytological diagnosis, and improves its accuracy in cervical cancer screening.

Evaluation of an isothermal amplification HPV detection assay for primary cervical cancer screening.

OBJECTIVE: The aim of this research was to evaluate independently the performance of a new isothermal amplification assay for cervical cancer screening compared to two previously validated PCR-based assays and histologic endpoints. METHODS: This is a sub-study from the Chinese multi-center screening trial (CHIMUST). The self-collected and clinician-collected specimens stored in PreservCyt at - 4 °C from 6042 women with complete data were tested with the AmpFire assay. These specimens had been previously tested with Cobas and SeqHPV assays. In the primary study all patients with an abnormal test were referred to colposcopy where all had directed and/or random biopsies plus ECC. No additional patients were called back based on the AmpFire results. RESULTS: 6042/6619 women had complete data (mean age 44.1). There were 57 cases of CIN 2, 35 cases of CIN 3 and 2 cancers. The sensitivity for CIN2+ and CIN3+ were similar among the three assays (both direct and self-collected). For the specificities in all categories (CIN2+/CIN3+ and self and direct collection), isothermal amplification assay was either equal to or more specific than Cobas but consistently less specific than SeqHPV. CONCLUSION: The AmpFire HPV assay showed similar sensitivity to Cobas and SeqHPV for CIN2+ and CIN3+ on both self and clinician-collections (P>0.05), with good specificity. The speed, low cost, and simplicity of this assay will make it particularly suited for low and middle resource settings. Its accuracy with self-collection makes it applicable for mass screening programs.

Colposcopy.

Though in the 1980s, colposcopically-directed biopsy excluded over 90% of CIN 3 and cancer (CIN 3+), recent reviews found sensitivity of colposcopically-directed biopsy for CIN 3+ of 50-65%. Studies from China showed that the sensitivity of colposcopically-directed biopsy for CIN 3+ is higher for large CIN 3+ than for small CIN 3+ and higher for associated high-grade cervical cytology than for low-grade cervical cytology. Colposcopically-directed biopsy excluded over 90% of CIN 3+ in the 1980s because colposcopy clinics in the 1980s evaluated women with high-grade cytology that had large CIN 3+; it no longer excludes CIN 3+ well because current colposcopy clinics evaluate women with low-grade cytology that have small CIN 3+. When colposcopically-directed biopsy is used to exclude CIN 3+ our understanding of the natural history of CIN is skewed, errors occur in defining appropriate screening practice, and inaccurate diagnosis results in incorrect treatment. The impression that CIN is more common on the anterior lip of the cervix is an artifact introduced by the inaccuracy of colposcopy. An unjustified enthusiasm for screening with acetic acid aided visual inspection (VIA) occurred when the sensitivity of VIA for CIN 3+ was inflated by screening studies using colposcopically-directed biopsy as the gold-standard for CIN 3+. To limit the harm of inaccurate diagnosis associated with colposcopically-directed biopsy, at colposcopy we advise random biopsies at the squamocolumnar junction in cervical quadrants without visible lesions and, unless the woman is pregnant, endocervical curettage (ECC). As the diagnosis of CIN 3+ solely by ECC is uncommon in women under age 25, the ECC may be omitted in women under age 25 years. If multiple cervical biopsies are performed, to limit discomfort, a bronchoscopy biopsy instrument which obtains 2-mm biopsies should be used.

Total laparoscopic hysterectomy versus laparoscopic-assisted vaginal hysterectomy in endometrial cancer: surgical and survival outcomes.

STUDY OBJECTIVE: To compare surgical and survival outcomes of patients with early-stage endometrial cancer (EC) who underwent total laparoscopic hysterectomy (TLH) or laparoscopic-assisted vaginal hysterectomy (LAVH) +/- lymphadenectomy. DESIGN: Retrospective, nonrandomized clinical study (Canadian Task Force classification II-2). SETTING: Two tertiary care academic medical centers. PATIENTS: Patients with EC treated by TLH or LAVH from 1998 through 2006. INTERVENTIONS: TLH and LAVH were performed in 80 and 24 patients, respectively. Patient demographics and clinical variables were collected, and surgical and survival outcomes were determined. MEASUREMENTS AND MAIN RESULTS: Median operating time was significantly higher for patients undergoing LAVH than for those undergoing TLH (212.5 and 183.5 minutes, respectively; p = .039). EBL was also greater in patients undergoing LAVH (median 220 mL) compared with those undergoing TLH (median100 mL; p = .001). After a median follow-up time of 51.5 months, there was no difference in recurrence or survival rates between the groups. CONCLUSION: Early-stage EC can be treated effectively with either TLH or LAVH. TLH patients may experience shorter operating times and less blood loss. When performed by experienced laparoscopists, TLH may be more feasible than LAVH in this cohort of patients.

Lysophosphatidic acid downregulates tissue inhibitor of metalloproteinases, which are negatively involved in lysophosphatidic acid-induced cell invasion.

Ovarian cancer is a highly metastatic disease. Lysophosphatidic acid (LPA) levels are elevated in ascites from ovarian cancer patients, but its potential role in ovarian cancer metastasis has just begun to be revealed. In this work, we show that LPA stimulates invasion of primary ovarian cancer cells, but not ovarian epithelial or borderline ovarian tumor cells, although these benign cells indeed respond to LPA in cell migration. We have found that LPA downregulates tissue inhibitor of metalloproteinases (TIMPs). TIMP2 and TIMP3 play functional role in LPA-induced invasion as negative regulators. G(i) protein, phosphatidylinositol-3 kinase (PI3K), p38 mitogen-activated protein kinase (MAPK), cytosolic phospholipase A(2) and urokinase type plasminogen activator (uPA) are required for LPA-induced cells invasion. TIMP3 may affect two independent downstream targets, vascular endothelial growth factor receptor and p38 MAPK. In vivo, LPA stimulates tumor metastasis in an orthotopic ovarian tumor model, which can be inhibited by a PI3K inhibitor, LY294002. In summary, LPA is likely a key component for promoting ovarian metastasis in vivo. LPA downregulates TIMP3, which may have targets other than metalloproteinases. Our in vivo metastasis mouse model is useful for studying the efficacy of therapeutic regimes of ovarian cancer.

Optical coherence tomography as a diagnostic aid to visual inspection and colposcopy for preinvasive and invasive cancer of the uterine cervix.

The purpose of this study was to determine the sensitivity and specificity of optical coherence tomography (OCT) under two well-defined clinical settings. First, as an aid to cervical cancer screening, using visual inspection with acetic acid (VIA) in low-resource settings, and the second, as an adjunct to the traditional management of abnormal cervical cytology with colposcopy and biopsy. Patients referred for colposcopy with > or = atypical squamous cells of undetermined significance were accrued for the study. Each subject underwent VIA and colposcopy. OCT was performed in all VIA- and colposcopy-positive areas and at the squamocolumnar junction in all four quadrants. The sensitivity of VIA for > or = cervical intraepithelial neoplasia 2 was 76% (95% CI 58-88). When OCT was applied to VIA as a secondary screen, the specificity improved from 34% (95% CI 27-41) to 61% (95% CI 60-74). With liberal diagnostic criteria for the majority of the colposcopy examinations, OCT showed an even greater relative improvement in specificity. OCT proved to be a fair diagnostic modality (receiver operating characteristic curve 0.73) adjunctive to VIA and colposcopy. On the basis of the above findings, we believe that this technology could potentially show greatest utility in the management of cervical dysplasia in low-resource settings where a single episode of care is most desirable.

Diagnostic efficacy of optical coherence tomography in the management of preinvasive and invasive cancer of uterine cervix and vulva.

The purpose of this study was to understand the capabilities and utility of optical coherence tomography (OCT) in characterizing tissue in patients with precancer and cancer of the uterine cervix and vulva. OCT is an optical technique that uses low-coherence interferometer to develop a two-dimensional image of optical scattering from internal tissue microstructure. This study was designed to develop diagnostic criteria. Women undergoing colposcopic evaluation secondary to an abnormal Papanicolaou smear or visualized grossly abnormal vulvar lesion comprised the study population. Under colposcopic visualization, the OCT device was applied to normal regions in all patients and abnormal areas when present, and images were captured. Each subject then underwent multiple directed biopsies. Images were then reviewed and compared with matched histology. A total of 50 women were recruited for the study. Of the 50 patients evaluated, 18 had cervical intraepithelial neoplasia (CIN) II,III, 14 had CIN I, 13 had metaplasia/inflammation, two had invasive squamous cell carcinoma of the cervix, and three had a diagnosis of Paget's disease of the vulva. Analysis of the OCT images showed a repetitive pattern that represented normal squamous epithelium of the cervix in 100% of the normal biopsies. Images of the 18 patients with histologically proven CIN II,III showed an unstructured homogeneous highly backscattering region with fast attenuation of the signal in 16 (89%) of the patients. OCT is a new approach for the early identification of cervix and vulvar malignancies. Using information inherent to the returning photon signals from tissue, early morphological and light-scattering changes can be detected during tumorigenesis. It has the potential to be a true optical biopsy. If diagnostically comparable to a biopsy, then clearly the ability of OCT to provide a point of service diagnosis would serve a significant advantage.

Shanxi Province cervical cancer screening study II: self-sampling for high-risk human papillomavirus compared to direct sampling for human papillomavirus and liquid based cervical cytology.

The objective of this study was to compare the sensitivity and specificity of a new method for self-sampling for high risk human papillomavirus (HPV) with direct sampling and liquid based cervical cytology. In Shanxi Province, China, 8,497 women (ages 27-56) underwent a self-sample for HPV using a conical-shaped brush placed into the upper vagina and rotated. Three to sixteen months later the women were screened with liquid-based cytology and direct HPV tests. Subjects with any abnormal test underwent colposcopy and multiple biopsies. Mean age was 40.9 years. 4.4 percent of subjects had >or=CIN II, 26% a positive self-sample and 24% a positive direct test for HPV. The sensitivity for detection of >or=CIN II was 87.5% for self-sampling, and 96.8% for the direct test (P < 0.001). The specificity was 77.2% for the self-sample and 79.7% for the direct test. With an abnormal Pap defined as ASCUS or greater the sensitivity of the Pap for the detection of >CIN II was 88.3% and the specificity was 81.2%. We conclude that self-sampling for HPV is less sensitive for >CIN II than the direct test, but similar to liquid based cytology.

Patient acceptance of self-sampling for human papillomavirus in rural china.

OBJECTIVE.: To test a new survey instrument and determine the acceptance and potential barriers of cervicovaginal self-sampling for high-risk human papillomavirus in rural Chinese women. MATERIALS AND METHODS.: Data from thirteen survey questions assessed acceptance of the self-sampling procedure. Pain, comprehension, and cultural beliefs were potential barriers evaluated by the survey. RESULTS.: A total of 1,560 women were surveyed. The average and mode number of steps of the self-sampling procedure recalled was 5 (out of 7). Ninety-one percent preferred performing the test at a clinic versus their home. The major barrier encountered was related to the educational level of the women. CONCLUSIONS.: The measure performed well in this population. The self-collection brush was well accepted by these women. Education is the largest hurdle to overcome in implementing a self-sampling screening program.

Fatty acid composition of lysophosphatidic acid and lysophosphatidylinositol in plasma from patients with ovarian cancer and other gynecological diseases.

OBJECTIVE: We previously reported that plasma levels of total lysophosphatidic acid (LPA) represented a potential biomarker for ovarian cancer and other gynecological cancers [1]. However, total LPA is composed of different LPA species with distinct fatty acid chains. The major objective of the current study, therefore, was to determine whether one or more specific fatty acid LPA species was associated with disease or disease staging. If this was determined, these species could be useful in further improving the sensitivity and/or specificity of this biomarker for the diagnosis and/or prognosis of the disease. Because lysophosphatidylinositol (LPI) co-migrates with LPA, this study represents the analysis of combined molecular species from both lysolipid classes. METHODS: The patient population, sample collection, and analyses have been reported previously [1]. Lipids were hydrolyzed from the LPA band on thin-layer chromatography plates. The following individual fatty acid species were analyzed by gas chromatography: palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), linoleic acid (18:2), arachidonic acid (20:4), and docosahexaenoic acid (22:6). The LPA/LPI fatty acid composition levels were analyzed and compared with disease status. RESULTS: Distinct plasma LPA/LPI fatty acid chain species were not associated with ovarian or other gynecological cancers, compared to patients with benign gynecological disease or healthy controls. However, an increased presence of unsaturated fatty acids in plasma LPA/LPI was found in patients with late-stage or recurrent ovarian cancer and possibly with other gynecological cancers. CONCLUSIONS: Analysis of individual fatty acid species present in plasma LPA/LPI do not appear to enhance the sensitivity or specificity of total LPA/LPI as a marker for gynecological cancer detection. However, our results suggest that increased LPA/LPI species with unsaturated fatty acid chains may be associated with late-stage or recurrent ovarian cancer.

The effect of radiation therapy on brain metastases from endometrial carcinoma: a retrospective study.

OBJECTIVE: The objective of this study was to investigate the effectiveness of radiation therapy as a treatment for brain metastases from endometrial carcinoma. METHODS: Between July 1985 and November 1999, 10 patients with brain metastases from endometrial carcinoma were treated at the Cleveland Clinic. We reviewed the patient and tumor characteristics at the time of the primary diagnosis and the brain metastases diagnosis. For the 8 patients who received radiation therapy with or without surgery, we analyzed the treatment results with regard to survival and local control of the metastases. RESULTS: Brain metastases from endometrial carcinoma were commonly accompanied by uncontrolled local-regional disease and systemic metastases. Multiple brain lesions developed in 7 of 10 patients. Two patients were treated with surgery alone and had a median survival of 2.75 months (4 and 1.5 months) after the brain metastases diagnosis. Three patients were treated with surgery and radiation therapy and lived for a median survival of 15 months (range 11.5 to 15.5 months). The 5 patients who were treated with radiation therapy without surgery had a median survival of 2.4 months (range 0.25 to 6 months). Patients with multiple brain metastases had a shorter survival than patients with a single metastasis. CONCLUSION: Overall survival after brain metastases development in patients with endometrial carcinoma was poor. Although the number of patients was small, radiation therapy alone resulted in poor survival. Combination treatment with surgery and radiation therapy may improve survival for selected patients.

Shanxi Province Cervical Cancer Screening Study: a cross-sectional comparative trial of multiple techniques to detect cervical neoplasia.

OBJECTIVE: The aim of this study was to design a cervical cancer screening algorithm for the developing world that is highly sensitive for cervical intraepithelial neoplasia (CIN) II, III, and cancer and highly specific for CIN II and III, making it possible to ablate the transformation zone without histologic confirmation. METHODS: In rural Shanxi Province, China, we examined 1997 women ages 35-45. Each subject underwent a self-test for intermediate and high-risk HPV (by HC-II assay), fluorescence spectroscopy, a liquid-based Pap (read manually and by computer and used as a direct test for HPV), a visual inspection (VIA) diagnosis, and colposcopy with multiple cervical biopsies. RESULTS: Mean age was 39.1 +/- 3.16 years, mean number of births was 2.6 +/- 0.93. Based on tests administered, 4.3% subjects had > or =CIN II. All subjects with > or =CIN II had either a ThinPrep Pap (> or =ASCUS) or a positive HPV direct test. The sensitivity and specificity for the detection of > or =CIN II were, respectively, 83 and 86% for the HPV self-test, 95 and 85% for the HPV direct test, 94 and 78% for the ThinPrep Pap (> or =ASCUS), 77 and 98% for the ThinPrep Pap (> or =HGSIL), 94 and 9% for fluorescence spectroscopy, 71 and 74% for VIA, and 81 and 77% for colposcopy. CONCLUSION: Based on these data and the existing healthcare infrastructure in China, we believe that further refinement of primary HPV screening using centralized labs is indicated. Self-testing in the local villages may be effective with improvements in the devices and techniques.

The colposcopic impression. Is it influenced by the colposcopist's knowledge of the findings on the referral Papanicolaou smear?

OBJECTIVE: To determine whether the colposcopic impression is influenced by the colposcopist's knowledge of the referral Papanicolaou smear. STUDY DESIGN: Using a community hospital database, the accuracy of the colposcopic impression (accuracy = proportion of women with histology greater than cervical intraepithelial neoplasia [CIN] 2 that have colposcopic impressions of greater than CIN 2) when referral smears were atypical squamous cells of uncertain significance (ASCUS), atypical glandular cells of uncertain significance (AGUS) or low grade squamous intraepithelial lesion (LSIL) was compared to that when smears showed high grade squamous intraepithelial lesion (HSIL) or cancer. The analysis was repeated with a screening study database in which colposcopic impression was assigned without knowledge of the Papanicolaou smear. Univariate and logistic regression analysis of the second database determined the relative importance of size and grade of lesion and Papanicolaou result to the accuracy of the colposcopic impression. RESULTS: In the community database, colposcopic accuracy was 60/510 (12%) when smears were ASCUS, AGUS or LSIL and 77/132 (58%) when smears were HSIL or cancer (P < .001); in the second database, it was 2/19 (11%) when smears subsequently were reported as negative, ASCUS, AGUS or LSIL and 33/65 (54%) when smears were HSIL or cancer (P < .005). An accurate colposcopic impression was seen in 5/39 (13%) women with one-quadrant lesions, 8/18 (44%) with two-quadrant lesions and 23/27 (85%) with three- or four-quadrant lesions (P < .005). None of 19 women with smears reported as negative, ASCUS, AGUS or LSIL had lesions involving three or four quadrants of the cervix, while 27/65 (42%) women with smears reported as HSIL or cancer had such lesions (P < .005). With logistic regression, the more quadrants of the cervix involved, the more accurate the colposcopic impression. Once controlled for lesion size, there was no improvement when worst histologic grade or Papanicolaou smear result was considered. CONCLUSION: Through lesions greater than CIN 2 were more often overlooked when referral smears were negative, ASCUS, AGUS or LSIL than when they were HSIL or cancer, the real reason that the lesions were not detected by colposcopy was that they were small.

Cervical cancer screening by simple visual inspection after acetic acid.

OBJECTIVE: To estimate the sensitivity and specificity of visual inspection using acetic acid as a primary screen for cervical intraepithelial neoplasia (CIN). METHODS: Visual inspection was done on 1997 women aged 35-45 years in a screening trial in rural China. Each women had colposcopy and at least five cervical biopsies (directed biopsy of lesions, one biopsy at 2, 4, 8, or 10 o'clock at the squamocolumnar junction in each normal quadrant, and an endocervical curettage). RESULTS: Forty-three women had biopsy-proven CIN II, 31 had CIN III, and 12 had invasive cancer. In two women only the endocervix was positive (one with CIN II and one with CIN III). Visual inspection yielded normal results in 1445 women (72%), low-grade intraepithelial neoplasia in 525 (26%), high-grade in 21 (1%), and cancer in six (0.3%). With abnormal visual inspection defined as low-grade intraepithelial neoplasia or worse, the sensitivity for detecting biopsy proven CIN II or worse was 71% (61 of 86, 95% confidence interval [CI] 60%, 80%); the specificity was 74% (1420 of 1911, 95% CI 72%, 76%); the sensitivity was 65% for smaller lesions (37 of 57, 95% CI 51%, 77%), and 89% for larger lesions (24 of 27, 95% CI 71%, 98%) (P =.03). CONCLUSION: The sensitivity of visual inspection equaled or exceeded reported rates for conventional cervical cytology. Visual inspection and colposcopy have similar specificity profiles for CIN II and greater. The benefit of an inexpensive point-of-care diagnosis and treatment algorithm will be a powerful incentive to pursue visual inspection for cervical cancer screening in developing countries.

Carboplatin skin testing: a skin-testing protocol for predicting hypersensitivity to carboplatin chemotherapy.

PURPOSE: A high incidence of moderate to severe hypersensitivity reactions (HRs) is noted in patients who have been treated with multiple courses of carboplatin. Presently, there is no reliable way to predict which patients may be at risk for this potentially severe adverse reaction. We developed a skin-test protocol to identify patients at high risk for HR to carboplatin chemotherapy. PATIENTS AND METHODS: Patients undergoing more than seven courses of carboplatin received a 0.02-mL intradermal injection of an undiluted aliquot of their planned carboplatin infusion 1 hour before each course of the agent. A positive skin test was prospectively defined as that resulting in a wheel of at least 5 mm with a surrounding flare. We recently reported a 27% incidence of HRs in patients receiving more than seven courses of carboplatin. These patients served as historical controls for the current study. RESULTS: Forty-seven patients with recurrent ovarian or primary peritoneal carcinoma receiving carboplatin were skin tested. Thirteen of 47 patients (28%) manifested a positive skin test at a median of nine total courses of carboplatin (range, eight to 17 courses). This rate of skin-test positivity was not significantly different from the incidence of documented HR reported in a historical control group (P =.89), suggesting comparable populations. A negative skin test accurately predicted the absence of HR in 166 of 168 courses of chemotherapy. Only two of 47 patients (4%) experienced a HR after a negative skin test. Thus, administering carboplatin only to patients with a negative skin test may result in a significant reduction in HRs relative to historical controls (P =.002). CONCLUSION: An easily performed skin test appears to predict patients in whom carboplatin may be safely administered. Treatment modifications based on the results of skin testing may reduce the incidence of HRs in patients receiving repeated courses of carboplatin.