Performance of a handheld point of care ultrasonography to assess IUD position compared to conventional transvaginal ultrasonography.

OBJECTIVE: To compare the performance of the abdominal handheld point-of-care ultrasonography (POCUS) Butterfly-iQ to gold standard transvaginal ultrasonography (US) in identifying the position of intrauterine devices (IUDs) in the hands of a medical doctor specialised in ultrasonography. METHODS: In this diagnostic accuracy study, a single operator conducted abdominal POCUS followed by conventional transvaginal US. Seventy patients utilising copper or hormonal IUDs were assessed between June 2021 and October 2022. IUDs were categorised as entirely within the uterine cavity or malpositioned. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated for detecting malpositioned IUDs, with conventional US results serving as the reference standard. Concordance rate and Kappa coefficient were computed to assess the agreement between the two ultrasound modalities. RESULTS: Among the 70 patients, 46 (65.7%) used copper IUDs, and 24 (34.3%) used hormonal IUDs. Conventional transvaginal US showed IUDs entirely within the uterine cavity in 56 (80%) patients and 14 (20%) IUDs were malpositioned. Of the 14 malpositioned IUDs seen by conventional US, POCUS identified 13 demonstrating a sensitivity of 92.9% (66.1-99.8). Of the 56 IUDs entirely within the uterine cavity shown by conventional US, only two cases were considered malpositioned by POCUS demonstrating a specificity of 96.4% (87.7-99.6). The concordance rate was 95.7%, and the Kappa value was 0.87 in differentiating between IUDs entirely within the uterine cavity and those that were malpositioned. CONCLUSION: Abdominal POCUS using Butterfly-iQ, when administered by an imaging specialist, exhibited excellent performance in confirming IUDs entirely within the uterine cavity.

Through a smartphone-based handheld point-of-care ultrasonography it was possible to correctly evaluate the position of intrauterine devices (IUDs) in a sample of 70 patients (46 using copper and 24 using hormonal IUDs).

Diagnosis of placenta accreta spectrum in high-risk women using ultrasonography or magnetic resonance imaging: systematic review and meta-analysis.

OBJECTIVES: To perform a systematic review and meta-analysis of the diagnostic test accuracy of ultrasound and magnetic resonance imaging (MRI) and compare the performance of the two modalities in the diagnosis of placenta accreta spectrum (PAS). METHODS: This was a systematic review conducted following the Cochrane Diagnostic Test Accuracy Reviews guideline. A literature search was performed in five databases: PubMed, EMBASE, PMC, The Cochrane Library and BVS-Bireme between 27 July and 4 August 2020. The search was updated on 18 August 2021. We included observational studies evaluating diagnostic accuracy in women with risk factors for PAS who had undergone both ultrasound and MRI examinations, published in English between 2011 and 2021. Quality Assessment of Diagnostic Accuracy Studies-2 was used to evaluate the quality of the studies. Forest plots for sensitivity and specificity with 95% CIs and receiver-operating-characteristics curves for ultrasound and MRI were constructed. RESULTS: The literature search identified 266 studies. After reviewing the titles and abstracts of the articles, 51 were selected for full-text review and 17 studies including 1301 women with MRI and ultrasound data available were selected for the meta-analysis. The study population included 457 cases with PAS diagnosed using the gold standard method (intraoperative or histopathological analysis). The overall quality of the evaluated studies was considered satisfactory according to QUADAS-2. The meta-analysis revealed a sensitivity of 0.833 (95% CI, 0.776-0.878) and specificity of 0.834 (95% CI, 0.746-0.897) for ultrasound. For MRI, sensitivity was 0.838 (95% CI, 0.786-0.879) and specificity was 0.831 (95% CI, 0.770-0.878). There was no statistically significant difference between the two modalities. The Cochran's Q values indicated a high level of heterogeneity of sensitivity and specificity of ultrasound and MRI across studies. CONCLUSIONS: Ultrasound and MRI have similar accuracy in the diagnosis of PAS. These results suggest that, in a setting with a high prevalence of risk factors, the choice of imaging modality for initial screening for PAS should depend on the availability of equipment and the examiner's expertise. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Performance of the IOTA ADNEX model in preoperative discrimination of adnexal masses in a gynecological oncology center.

OBJECTIVE: To evaluate the performance of the International Ovarian Tumor Analysis (IOTA) ADNEX model in the preoperative discrimination between benign ovarian (including tubal and para-ovarian) tumors, borderline ovarian tumors (BOT), Stage I ovarian cancer (OC), Stage II-IV OC and ovarian metastasis in a gynecological oncology center in Brazil. METHODS: This was a diagnostic accuracy study including 131 women with an adnexal mass invited to participate between February 2014 and November 2015. Before surgery, pelvic ultrasound examination was performed and serum levels of tumor marker CA 125 were measured in all women. Adnexal masses were classified according to the IOTA ADNEX model. Histopathological diagnosis was the gold standard. Receiver-operating characteristics (ROC) curve analysis was used to determine the diagnostic accuracy of the model to classify tumors into different histological types. RESULTS: Of 131 women, 63 (48.1%) had a benign ovarian tumor, 16 (12.2%) had a BOT, 17 (13.0%) had Stage I OC, 24 (18.3%) had Stage II-IV OC and 11 (8.4%) had ovarian metastasis. The area under the ROC curve (AUC) was 0.92 (95% CI, 0.88-0.97) for the basic discrimination between benign vs malignant tumors using the IOTA ADNEX model. Performance was high for the discrimination between benign vs Stage II-IV OC, BOT vs Stage II-IV OC and Stage I OC vs Stage II-IV OC, with AUCs of 0.99, 0.97 and 0.94, respectively. Performance was poor for the differentiation between BOT vs Stage I OC and between Stage I OC vs ovarian metastasis with AUCs of 0.64. CONCLUSION: The majority of adnexal masses in our study were classified correctly using the IOTA ADNEX model. On the basis of our findings, we would expect the model to aid in the management of women with an adnexal mass presenting to a gynecological oncology center. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Ultrasound criteria and CA 125 as predictive variables of ovarian cancer in women with adnexal tumors.

OBJECTIVES: To evaluate the capacity to predict malignancy in women with adnexal tumors using CA 125 measurement and ultrasound criteria. METHODS: This was a cross-sectional study including 103 women with a total of 110 adnexal tumors. CA 125 level was measured in a sample of peripheral blood. Lesions were classified by ultrasound, using standardized predetermined criteria, as benign (B) or malignant (M). Those that could not be classified by these criteria were assessed subjectively. Histopathologic examination of surgical specimens was used as the gold standard. RESULTS: Of 110 tumors, 79 (71.8%) were benign and 31 (28.2%) were malignant on histopathology. Ultrasound criteria could be applied to 91 (82.7%) tumors, resulting in a sensitivity of 90%, specificity of 87%, positive predictive value (PPV) of 69% and negative predictive value (NPV) of 97%. In tumors not classifiable according to ultrasound criteria, subjective sonographic assessment gave a sensitivity of 67%, specificity of 80%, PPV of 75% and NPV of 73%. At a cut-off point of 37.4 U/mL, CA 125 had a sensitivity of 69%, a specificity of 87.8%, a PPV of 69% and a NPV of 88% for detection of malignancy. When CA 125 was associated with age and ultrasound criteria in a logistic regression model, the sensitivity and specificity increased in the subset of sonographically malignant tumors. CONCLUSION: The majority of tumors were correctly classified using ultrasound criteria. CA 125 alone performed worse than did ultrasound in discriminating malignant from benign adnexal tumors. CA 125 measurement contributed to the diagnosis of malignancy, improving overall specificity, only in sonographically malignant tumors.

Self-sampling for human papillomavirus (HPV) testing as cervical cancer screening option. Experience from the LAMS study.

PURPOSE: To compare Hybrid Capture II (HC2) in detecting high-risk (HR) HPV in patient-collected vaginal samples with those obtained using gynaecologist collected samples. METHODS: Patients were submitted to Pap smears, visual inspection with acetic acid (VIA) and HC2 for hr-HPV. RESULTS: A total of 1,081 HC2 tests for HR-HPV were performed: 770 (71.2%) samples were collected by a physician and 311 (28.8%) were self-collected by the patients. In detecting any cervical lesion, the sensitivity of HC2 collected by a physician was higher (92.86%) than that (37.5%) in the self-sampling group. Negative predictive value (NPV) was high for both, 99.69% and 93.75%, respectively. Using the CIN2 cutoff, performance of HC2 was significantly improved: 92.9% and 62.5%, respectively. HC2 specificity for any cervical lesion and for CIN2 or higher were close to 90% in both groups. CONCLUSIONS: Self-sampled HPV testing is a powerful option to increase the detection of cervical lesions in women segregated from prevention programs.

Safety of screening with Human papillomavirus testing for cervical cancer at three-year intervals in a high-risk population: experience from the LAMS study.

OBJECTIVES: To assess whether human papillomavirus (HPV) testing is a safe enough approach to warrant extension of the screening intervals of baseline Papanicolaou (Pap)-/HPV- women in low-income settings. METHODS: Of the >1000 women prospectively followed up as part of the Latin American Screening (LAMS) Study in São Paulo, Campinas, Porto Alegre) and Buenos Aires, 470 women with both baseline cytology and Hybrid Capture 2 (HC2) results available were included in this analysis. These baseline Pap-negative and HC2- or HC2+ women were controlled at six-month intervals with colposcopy, HC2 and Pap to assess the cumulative risk of incident Pap smear abnormalities and their predictive factors. RESULTS: Of the 470 women, 324 (68.9%) were high-risk HPV (hrHPV) positive and 146 (31.1%) were negative. Having two or more lifetime sex partners (odds ratio [OR] = 2.63; 95% CI 1.70-3.51) and women using hormonal contraception (OR = 2.21; 95% CI 1.40-3.51) were at increased risk for baseline hrHPV infection. Baseline hrHPV+ women had a significantly increased risk of incident abnormal Pap smears during the follow-up. Survival curves deviate from each other starting at month 24 onwards, when hrHPV+ women start rapidly accumulating incident Pap smear abnormalities, including atypical squamous cells (ASC) or worse (log-rank; P < 0.001), low-grade squamous intraepithelial lesions (LSIL) or worse (P < 0.001) and high-grade squamous intraepithelial lesions (HSIL) (P = 0.03). Among the baseline hrHPV- women, the acquisition of incident hrHPV during the follow-up period significantly increased the risk of incident cytological abnormalities (hazard ratio = 3.5; 95% CI 1.1-11.7). CONCLUSION: These data implicate that HPV testing for hrHPV types might be a safe enough approach to warrant extension of the screening interval of hrHPV-/Pap-women even in low-resource settings. Although some women will inevitably contract hrHPV, the process to develop HSIL will be long enough to enable their detection at the next screening round (e.g. after three years).

Endocervical glandular cell abnormalities in conventional cervical smears: evaluation of the performance of cytomorphological criteria and HPV testing in predicting neoplasia.

OBJECTIVE: To analyse the correlation between cytomorphological criteria in smears with atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) and human papillomavirus (HPV) reflex test results with different neoplastic histological diagnoses, particularly to distinguish between glandular and squamous neoplasia. METHODS: A series of 155 women with glandular abnormalities in their conventional cervical smears was included: 106 with AGC, 35 with AGC associated with high-grade squamous intraepithelial lesion (HSIL) and 14 with AIS. Two reviewers evaluated 35 cytomorphological criteria and hybrid capture II (HCII) was performed in all cases. Colposcopy was carried out in all cases and biopsy in 126/155. For statistical purposes, predictive values and odds ratio (OR) were calculated, followed by chi-square automatic interaction detection. RESULTS: Histology detected 56 cases of squamous and 17 of glandular intraepithelial or invasive neoplasia. Predictive values of the papillary groups and feathering criteria for glandular neoplasia were, respectively, 80.0% and 73.3%. Feathering was the criterion with the highest OR for distinguishing glandular from squamous neoplasia and also for distinguishing between glandular and non-neoplastic diagnosis. Rosettes and pseudostratified strips did not perform as well. Multivariant Classification and Regression Trees analysis identified feathering as the best criterion for distinguishing between glandular, squamous and non-neoplastic diagnoses regardless of HPV status. CONCLUSIONS: Feathering was the best criterion for predicting glandular neoplasia.

Expression of p16 and cervical infection with high-risk human papillomavirus are not related to p53 activity in cervical intraepithelial neoplasia.

The objective of the study was to investigate the expression of p53 and p16(INK4a) in cervical intraepithelial neoplasia (CIN) and their relation with disease severity and high-risk human papillomavirus (HR-HPV) status. A series of 125 women with previous positive Pap smear were selected for this cross-sectional study. All patients underwent gynecological examination, including colposcopy. Specimens for Pap smears, Hybrid Capture 2 (HC2) test, and pathologic analysis were obtained. After evaluation of CIN grade, immunohistochemical detection of proteins p53 and p16(INK4a) was performed on paraffin-embedded sections. The extent of immunoexpression of both proteins was analyzed in relation to CIN grade and HR-HPV status. CIN was graded as 1 in 21, 2 in 17, and 3 in 87 specimens. p16(INK4a) positivity (at least 5% of epithelial cells stained) was found in 99 of 125 cases (79.2%) and was significantly higher in high-grade lesions as compared to low-grade CIN (P < 0.001). The expression of p53 did not differ across histologic strata. Protein expression neither of p16(INK4a) nor of p53 correlated with HR-HPV status. Expression of p16(INK4a) was not related with that of p53. Our study gives further support to previous findings of strong association of p16(INK4a) immunostaining with severity of epithelial atypia, but this protein may not be considered a predictor of HR-HPV status determined with HC2. By contrast, immunoexpression of p53 was related neither to CIN grade nor to HR-HPV status.

Cell proliferation activity unrelated to COX-2 expression in ovarian tumors.

The objective of this study was to assess the expression of Cyclooxygenase-2 (COX-2) and cell proliferation activity (Ki67 expression) in benign, borderline, and malignant serous and mucinous ovarian tumors. Expression of COX-2 and Ki67 proteins were evaluated by immunohistochemistry, in paraffin-embedded sections of ovarian epithelial tumors. The study included 113 serous (67 benign, 15 borderline, and 31 malignant) and 85 mucinous (48 benign, 28 borderline, and 9 malignant) tumors, removed from women who underwent laparotomy between January 1997 and December 2003. From benign to malignant tumors, there was a progressive positive trend in COX-2 expression in both serous and mucinous tumors, more evident in mucinous ones (P < 0.001). Comparing histologic types, COX-2 expression was more prominent in serous than in mucinous benign tumors (P < 0.01), but this difference was not significant in the borderline (P= 0.11) or malignant categories (P= 0.71). There was a progressive Ki67 positivity in line with the tumor histologic gradient for both serous (P < 0.01) and mucinous lesions (P < 0.01), but this increasing expression did not correlate with COX-2 expression in the present series (P= 0.78). There was a higher COX-2 expression in serous ovarian adenomas than in mucinous ones. COX-2 positivity increases in line with the morphologic gradient, from benign to malignant in both histologic types, but it was more prominent in mucinous lesions, pointing to different oncogenic pathways related to different histologic types. A correlation between the expression of COX-2 and Ki67 was not found, suggesting that COX-2 may be required for carcinogenesis, but this pathway is not responsible for cell proliferation in ovarian tumors.

Prediction of high-grade cervical disease with human papillomavirus detection in women with glandular and squamous cytologic abnormalities.

The objective of this study was to assess whether human papillomavirus (HPV) detection with hybrid capture II (HC II) can help predict the presence and the nature, glandular or squamous, of histologic cervical lesions in women referred due to atypical glandular cells (AGC) or high-grade squamous intraepithelial lesion (HSIL). A total of 247 women were included. Referral Pap smears comprised AGC (51 cases), AGC plus HSIL (28 cases), adenocarcinoma in situ (10 cases), and HSIL (158 cases). All patients were tested for high-risk HPV with HC II and had a histologic assessment of their cervix. Histologic analysis showed 38 women with (15.3%) cervicitis, 194 with (75.5%) squamous lesions, and 15 with (9.2%) glandular neoplasia. The overall rate of high-risk HPV detection was 77%. Almost 70% of AGC-HPV-negative patients did not have a pathologically proven cervical neoplasia, whereas 76% of women with AGC-HPV-positive result were diagnosed with a squamous or glandular neoplasia. Most (95%) of the lesions in patients with AGC-HSIL were of squamous nature, and HPV detection did not contribute to their differentiation from glandular lesions. We conclude that in women with AGC, HPV positivity strongly correlated with the presence of glandular or squamous cervical lesion but did not help distinguishing women with squamous from those with glandular neoplasia.

Human papillomavirus testing as an optional screening tool in low-resource settings of Latin America: experience from the Latin American Screening study.

Hybrid capture II (HC II) test for oncogenic human papillomaviruses (HPV) was carried out in a cohort of 4284 women at their first clinical visit. Overall prevalence of HPV was 17.1%, decreasing with age from 33.9% among women below 20 years to only 11.0% among those older than 41 years. HPV prevalence was significantly higher among current smokers (odds ratio [OR] = 1.31; 95% CI 1.1-1.6), in women with two or more lifetime sexual partners (OR = 1.9; 95% CI 1.6-2.4), and those women with two or more sexual partners during the past 12 months prior to examination (OR = 1.6; 95% CI 1.2-2.2). HPV detection increased in parallel with increasing cytologic abnormality, being highest in women with high-grade squamous intraepithelial lesion (P= 0.001). Specificity of the HPV test in detecting histologically confirmed cervical disease was 85% (95% CI 83.9-86.1). Sensitivity of the HPV test in detecting histologic abnormalities increased in parallel with disease severity, ranging from 51.5% for cervical intraepithelial neoplasia (CIN) 1 to 96.5% for CIN 3 and 100.0% for cancer, with respective decline of positive predictive value. These data suggest that HPV testing with HC II assay might be a viable screening tool among this population with relatively high prevalence of cervical disease.

Evaluation of visual inspection with acetic acid (VIA), Lugol's iodine (VILI), cervical cytology and HPV testing as cervical screening tools in Latin America. This report refers to partial results from the LAMS (Latin AMerican Screening) study.

OBJECTIVES: To assess the performance indicators of visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI) in four Latin American centres participating in the ongoing Latin AMerican Screening (LAMS) study, in settings with moderate incidence of cervical disease and with poorly to moderately well-organized cervical cancer screening. SETTING: Three Brazilian centres (São Paulo, Campinas and Porto Alegre) and one Argentine centre (Buenos Aires) recruited a total of 11,834 healthy women to undergo VIA, VILI, conventional Pap smear and Hybrid Capture II (HCII). METHODS: Women who had a positive result from any of these tests were subjected to colposcopy and biopsies (if necessary), and women with high-grade cervical intraepithelial neoplasia (CIN) were properly treated. To control for verification bias, 5% of women with normal tests were referred for colposcopy, as were 20% of HCII-negative women. RESULTS: Data on VIA (n=11,834), VILI (n=2994), conventional Pap smear (n=10,138) and HCII (n=4195) were available for test comparisons, calculating sensitivity, specificity, and positive and negative predictive values. Overall test positivity was 11.6% for VIA, 23.0% for VILI, 2.2% for Pap smear (LSIL threshold), 1.1% for Pap smear (HSIL threshold) and 17.1% for HCII. VIA was positive in 61.8% of the women with CIN 1, 57.0% of those with CIN 2, 35.0% of women with CIN 3 and in 21 of 28 (75%) of women with cancer. Approximately 10% of women with no detectable disease had an abnormal VIA. Regarding VILI, 83.3% of women diagnosed with CIN 1 and 62.5% of those with CIN 3 had an abnormal test. VILI failed to detect one of three cases of cancer. Both the sensitivity, specificity and positive predictive value of VIA and VILI in detecting CIN 2 or CIN 3 could be significantly improved depending on the combination with Pap smear or HCII (sensitivity up to 100.0% and specificity up to 99.8%). CONCLUSIONS: The LAMS study failed to reproduce the performance figures obtained with VIA and VILI (as stand-alone tests) in some other settings, where the prevalence of cervical disease was higher. However, a combined use of VIA or VILI with the Pap test or HCII allowed specific detection of cervical abnormalities.

Aided visual inspection with acetic acid (VIA) and HPV detection as optional screening tools for cervical cancer and its precursor lesions.

PURPOSE OF INVESTIGATION: To assess the contribution of visual inspection with acetic acid (VIA) and Hybrid Capture II (HCII) as adjunct methods to the Pap test in detecting cervical neoplasia. SUBJECTS AND METHODS: This was a cross-sectional study with 809 women who consecutively attended gynecological consultations at Campinas University, Brazil, from January 2002 to July 2003. Pap test, HCII, VIA, and colposcopy were offered to all patients. Performance of tests (alone or in combination) in detecting histologically confirmed lesions was evaluated. RESULTS: Of the 40 patients with CIN, 69% had CIN1, 26% CIN2 or CIN3 and one patient had invasive carcinoma. VIA had the best performance in detecting CIN, yielding 72% sensitivity and 91% specificity. Considering only CIN2 or worse as significant lesions, HCII had the best sensitivity (73%), while the Pap test was the most specific (93%). Combining the three exams, 92% of the CIN1 or worse were detected. When CIN1 was excluded from the analysis, Pap smear plus HCII delivered 82% sensitivity and 79% specificity. However, this combination yielded a very low (5%) PPV. CONCLUSION: VIA and HCII contributed to the screening of cervical neoplasia in a group of Brazilian women, but the cost-effectiveness of conjoint screening modalities is still debatable.