Objective: To evaluate the performance of point-of-care testing for cervical cancer and precancerous lesions screening. Methods: In September 2020, 197 and 273 women were selected by using simple random sampling method from "self-sampling" cohort and "physician-sampling" cohort established in Xiangyuan county, Shanxi Province, China, respectively. Cervical exfoliated cells were collected by women themselves or gynecologists. All samples were detected by POCT and women with positive result were directly referred for colposcopy. Subsequently, all the samples were detected by careHPV and PCR test. Colposcopy and punch biopsy were performed for women with POCT negative but careHPV or PCR test positive at another visit. Using histopathological diagnosis as the gold standard, we calculated sensitivity, specificity and drew the receiver operating characteristic (ROC) curves. The accuracy of POCT was analyzed and compared to that of careHPV and conventional PCR test in cervical cancer and precancerous lesions screening. Results: The median (Q₁ , Q₃) age of 470 women was 51 (45, 57) years old. Based on self-sampling, the sensitivity and specificity of POCT for CIN2+ were 100.00% (95%CI: 56.56%-100.00%) and 28.95% (95%CI: 22.97%-35.76%), respectively. Compared with POCT, POCT HPV16/18 test had similar sensitivity and higher specificity of 89.47% (95%CI: 84.30%-93.08%). Self-sampling POCT HPV16/18 test had an AUC of 0.947 (95%CI:0.910-0.985), which was higher than that of careHPV and PCR test. Physician-sampling POCT test had 100.00% sensitivity (95%CI: 64.57%-100.00%) and 55.85% specificity (95%CI: 49.83%-61.70%) for detecting CIN2+. POCT HPV16/18 test had lower sensitivity (71.43%, 95%CI: 35.90%-91.76%) and higher specificity (92.45%, 95%CI: 88.63%-95.06%). POCT HPV16/18 test generally showed similar AUC on both self-collected samples and clinician-collected samples (0.947 vs 0.819, P=0.217). Conclusion: POCT HPV16/18 test is an effective method with relatively high sensitivity and specificity for cervical cancer screening.
Cervical Intraepithelial Neoplasia/diagnosis* ; Colposcopy ; Early Detection of Cancer/methods* ; Female ; Human papillomavirus 16/genetics* ; Human papillomavirus 18 ; Humans ; Mass Screening/methods* ; Papillomaviridae ; Papillomavirus Infections/diagnosis* ; Point-of-Care Testing ; Pregnancy ; Sensitivity and Specificity ; Uterine Cervical Neoplasms

OBJECTIVE: To investigate pathologic discrepancies between colposcopy-directed biopsy (CDB) of the cervix and loop electrosurgical excision procedure (LEEP) in women with cytologic high-grade squamous intraepithelial lesions (HSILs).METHODS: We retrospectively identified 297 patients who underwent both CDB and LEEP for HSILs in cervical cytology between 2015 and 2018, and compared their pathologic results. Considering the LEEP to be the gold standard, we evaluated the diagnostic performance of CDB for identifying cervical intraepithelial neoplasia (CIN) grades 2 and 3, adenocarcinoma in situ, and cancer (HSIL+). We also performed age subgroup analyses.RESULTS: Among the study population, 90.9% (270/297) had pathologic HSIL+ using the LEEP. The diagnostic performance of CDB for identifying HSIL+ was as follows: sensitivity, 87.8%; specificity, 59.3%; balanced accuracy, 73.6%; positive predictive value, 95.6%; and negative predictive value, 32.7%. Thirty-three false negative cases of CDB included CIN2,3 (n=29) and cervical cancer (n=4). The pathologic HSIL+ rate in patients with HSIL− by CDB was 67.3% (33/49). CDB exhibited a significant difference in the diagnosis of HSIL+ compared to LEEP in all patients (p<0.001). In age subgroup analyses, age groups <35 years and 35–50 years showed good agreement with the entire data set (p=0.496 and p=0.406, respectively), while age group ≥50 years did not (p=0.036).CONCLUSION: A significant pathologic discrepancy was observed between CDB and LEEP results in women with cytologic HSILs. The diagnostic inaccuracy of CDB increased in those ≥50 years of age.
Adenocarcinoma in Situ ; Biopsy ; Cervical Intraepithelial Neoplasia ; Cervix Uteri ; Colposcopy ; Conization ; Dataset ; Diagnosis ; Early Detection of Cancer ; Female ; Humans ; Papanicolaou Test ; Retrospective Studies ; Sensitivity and Specificity ; Squamous Intraepithelial Lesions of the Cervix ; Uterine Cervical Neoplasms

OBJECTIVE: To screen potential plasma protein biomarkers for the progression of cervical precancerous lesions into cervical carcinoma and analyze their functions. METHODS: Plasma samples obtained from healthy control subjects, patients with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC), and patients with CC after treatment were enriched for low-abundance proteins for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The MS data of the samples were analyzed using Discoverer 2.2 software, and the differential proteins (peptide coverage ≥20%, unique peptides≥2) were screened by comparison of LSIL, HSIL and CC groups against the control group followed by verification using target proteomics technology. Protein function enrichment and coexpression analyses were carried out to explore the role of the differentially expressed proteins as potential biomarkers and their pathological mechanisms. RESULTS: Compared with the control group, both LSIL group and HSIL group showed 9 differential proteins; 5 differentially expressed proteins were identified in CC group. The proteins ORM2 and HPR showed obvious differential expressions in LSIL and HSIL groups compared with the control group, and could serve as potential biomarkers for the progression of cervical carcinoma. The expression of F9 increased consistently with the lesion progression from LSIL to HSIL and CC, suggesting its value as a potential biomarker for the progression of cervical cancer. CFI and AFM protein levels were obviously decreased in treated patients with CC compared with the patients before treatment, indicating their predictive value for the therapeutic efficacy. Protein function enrichment analysis showed that all these differentially expressed proteins were associated with the complement system and the coagulation cascades pathway. CONCLUSIONS We identified 5 new protein biomarkers (F9, CFI, AFM, HPR, and ORM2) for cervical precancerous lesions and for prognostic evaluation of CC, and combined detection of these biomarkers may help in the evaluation of the development and progression of CC and also in improving the diagnostic sensitivity and specificity of cervical lesions.
Antigens, Neoplasm ; blood ; Biomarkers, Tumor ; blood ; Carrier Proteins ; blood ; Case-Control Studies ; Cervical Intraepithelial Neoplasia ; blood ; diagnosis ; Chromatography, Liquid ; Complement Factor I ; analysis ; Early Detection of Cancer ; Female ; Glycoproteins ; blood ; Haptoglobins ; Humans ; Neoplasm Proteins ; blood ; Orosomucoid ; analysis ; Precancerous Conditions ; blood ; diagnosis ; Serum Albumin, Human ; Tandem Mass Spectrometry ; Uterine Cervical Neoplasms ; blood ; diagnosis

OBJECTIVE: To investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements. METHODS: Women with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152). RESULTS: There were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07–0.68; p=0.010). Women in their 40s–50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03–1.49; p=0.020). CONCLUSION: In women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years.
Atypical Squamous Cells of the Cervix* ; Biopsy ; Cervical Intraepithelial Neoplasia* ; Cohort Studies* ; Colposcopy ; Cryotherapy ; Curettage ; Diagnosis ; Ethics Committees, Research ; Female ; Humans ; Incidence ; Mass Screening ; National Health Programs ; Proportional Hazards Models ; Risk Reduction Behavior ; Taiwan ; Uterine Cervical Neoplasms ; Vaginal Smears

OBJECTIVE: To investigate the expression of claudin 4 (CLDN4) in cervical tissues from patients with different cervical lesions, and to explore the value of combined detection of CLDN4 and high risk human papilloma virus (HR-HPV). METHODS: The cervical tissue specimens of low-grade squamous intraepithelial lesion (LSIL, =30), high-grade squamous intraepithelial lesion (HSIL, =30), squamous cell carcinoma (SCC, =30) as well as chronic cervicitis (control, =30) were collected from the Sir Run Run Shaw Hospital of Zhejiang University during June 2015 and December 2016. The expression of CLDN4 protein in tissue specimens was detected by immunohistochemistry, HR-HPV was detected by real-time quantitative PCR, and the cervical exfoliated cells were examined by thinprep cytologic test (TCT). The ROC curve was applied to analyze the diagnostic value of TCT combined with HR-HPV and CLDN4 combined with HR-HPV tests for HSIL and SCC of the cervix. RESULTS: With the increase of the severity of cervical lesions, the positive rate of CLDN4 expression rose (=0.832, <0.05). Positivity of both HR-HPV infection and CLDN4 expression was found mainly in the HSIL and SCC groups. The areas under curve (AUC) of TCT combined with HR-HPV and CLDN4 combined with HR-HPV tests for diagnosis of HSIL and SCC were 0.683 and 0.633, respectively; the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of TCT combined with HR-HPV test for diagnosis of HSIL and SCC were 100.0%, 36.7%, 61.2%, 100.0% and 46.7% respectively; those of CLDN4 combined with HR-HPV test were 96.7%, 30.0%, 58.0%, 90.0% and 55.0%, respectively. CONCLUSIONS CLDN4 expression may be related to the occurrence and development of cervical carcinoma and precancerous lesions. CLDN4 combined with HR-HPV test may be used for diagnosis of HSIL and SCC of the cervix clinically.
Carcinoma, Squamous Cell ; diagnosis ; virology ; Cervical Intraepithelial Neoplasia ; diagnosis ; virology ; Claudin-4 ; genetics ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunochemistry ; Papillomaviridae ; isolation & purification ; Real-Time Polymerase Chain Reaction ; Squamous Intraepithelial Lesions of the Cervix ; virology ; Uterine Cervical Neoplasms ; diagnosis

OBJECTIVE: This study aimed to determine the factors affecting pathologic discrepancy and final diagnosis between colposcopic biopsy and pathology by loop electrosurgical excision procedure (LEEP). METHODS: Between 2004 and 2016, 1,200 patients who underwent LEEP were enrolled for this study. 667 underwent cervical cytology, human papillomavirus (HPV) test, colposcopic biopsy, and LEEP. We analyzed patient's age, menopausal status, number of delivery, abortion times, cervical cytology, number of punch biopsies, HPV type, LEEP, and interval between colposcopic biopsy and LEEP. RESULTS: Logistic regression analysis of the final diagnosis showed that age 30–39 years and other high HPV group types were associated with cancer diagnosis, whereas atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H), high-grade squamous intraepithelial lesion (HSIL), and HPV type 16 affected the diagnosis of cervical intraepithelial neoplasia (CIN) 2. The overall concordance rate of histopathology between punch biopsy and LEEP was 43.3%. The rates of detecting a more severe lesion by LEEP than those by biopsy were 23.1%. The rates of a less severe lesion detected by LEEP than those by biopsy were 33.6%. Factors related with biopsy underestimation were as follows: < 1 vaginal delivery, HSIL, number of punch biopsies and HPV type. Punch biopsy number is a unique factor of biopsy overestimation. CONCLUSION: Patients with ASC-H, HSIL, and HPV type 16 may undergo conization immediately without colposcopic biopsy. We suggest that colposcopically directed 3 to 5 punch biopsies may be used to determine the need for conization.
Atypical Squamous Cells of the Cervix ; Biopsy* ; Cervical Intraepithelial Neoplasia ; Cervix Uteri* ; Conization* ; Diagnosis ; Female ; Humans ; Logistic Models ; Papanicolaou Test ; Pathology ; Squamous Intraepithelial Lesions of the Cervix

BACKGROUND: Pyometra should be treated with caution in elderly patients because it may indicate a malignancy in the post-menopausal period and can result in life-threatening complications such as septicemia or pan-peritonitis. METHODS: We retrospectively analyzed the clinical features of 30 patients aged ≥65 years who received treatment for pyometra between January 2010 and December 2014. RESULTS: The 30 patients (age: median, 74 years; range, 66-88 years) were evaluated. They presented with vaginal discharge (n=17), vaginal bleeding (n=8), abdominal pain (n=6), or fever (n=3). The most common accompanying systemic disease was hypertension (n=15), followed by diabetes mellitus (n=10). Of the 30 cases, seven were associ- ated with gynecologic malignancy (cervical cancers, n=3; endometrial cancers, n=3; and ovarian cancer, n=1); and 14, with gynecologic benign diseases (uterine myoma, n=5; cervical intraepithelial neoplasia, n=4; tubo-ovarian abscess, n=3; endometrial polyp, n=1; uterine prolapse, n=1). All the patients were treated with cervical dilatation and drainage. Fifteen patients underwent gynecologic surgery with antibiotic therapy, and 15 received empirical antibiotic treatment alone. Two women experienced spontaneous perforation of pyometra. Pyometra is considered a complication of benign and malignant gynecologic disease, until proven otherwise. CONCLUSION: In elderly patients with comorbidities, pyometra might induce severe complications such as pan-peritonitis or sepsis. Early accurate diagnosis is important to determine an appropriate individualized treatment to reduce morbidity and mortality.
Abdominal Pain ; Abscess ; Aged* ; Cervical Intraepithelial Neoplasia ; Comorbidity ; Diabetes Mellitus ; Diagnosis ; Drainage ; Endometrial Neoplasms ; Female ; Fever ; Genital Diseases, Female ; Gynecologic Surgical Procedures ; Humans ; Hypertension ; Labor Stage, First ; Mortality ; Myoma ; Ovarian Neoplasms ; Peritonitis ; Polyps ; Postmenopause ; Pregnancy ; Pyometra* ; Retrospective Studies ; Sepsis ; Uterine Hemorrhage ; Uterine Prolapse ; Vaginal Discharge

BACKGROUND: Geographic variation in the prevalence of carcinogenic types and human papillomavirus (HPV) genotype distribution is closely associated with the impact of HPV prophylactic vaccines. We determined the prevalence and distribution of HPV genotypes among healthy women in Korea. METHODS: This study included 968 healthy women who were examined at a health promotion center of the Korea University Guro Hospital between January and June 2013. Each participant had a Pap test and a HPV DNA test using the Anyplex™ II HPV 28 Detection system, which detects 19 high-risk HPVs (HR HPVs) and 9 low-risk HPVs (LR HPVs). Women with abnormal cytology and/or positivity for HR HPVs were referred to colposcopic biopsy. RESULTS: Overall HR HPV prevalence based on the assay was 33.7%. Among them, 225 women had single infection and 101 women had multiple infection. The most frequently occurring HR HPV types were 53 (6.5%), 52 (6.1%), 58 (4.8%), 16 (4.5%), and 68 (4.2%). The most frequently occurring LR HPV types were 54 (5.4%), 70 (3.8%), 42 (3.6%), 61 (3.4%), and 44 (3.1%). The prevalence of HPV 16 was highest (17.6%) among women with cervical intraepithelial neoplasia (CIN) and HPV 16 was strongly associated with a diagnosis of CIN2/3 (odds ratio = 20.5; 95% confidence interval: 3.9-107.1; P < 0.0001). CONCLUSIONS: HPV 53, 52, 58, 16, and 68 were common HR HPV types among healthy Korean women. HPV16 was the most common type in high-grade CIN lesions, as shown in most studies worldwide. The results might be useful information for cervical cancer prevention in South Korea.
Biopsy ; Cervical Intraepithelial Neoplasia ; Diagnosis ; Female ; Genotype ; Health Promotion ; Human papillomavirus 16 ; Human Papillomavirus DNA Tests ; Humans* ; Korea* ; Papanicolaou Test ; Prevalence* ; Uterine Cervical Neoplasms ; Vaccines

BACKGROUND: Human papillomavirus (HPV) is a major risk factor for cervical cancer. METHODS: We evaluated the clinical significance of the HPV DNA chip genotyping assay (MyHPV chip, Mygene Co.) compared with the Hybrid Capture 2 (HC2) chemiluminescent nucleic acid hybridization kit (Digene Corp.) in 867 patients. RESULTS: The concordance rate between the MyHPV chip and HC2 was 79.4% (kappa coefficient, κ = 0.55). The sensitivity and specificity of both HPV tests were very similar (approximately 85% and 50%, respectively). The addition of HPV result (either MyHPV chip or HC2) to cytology improved the sensitivity (95%, each) but reduced the specificity (approximately 30%, each) compared with the HPV test or cytology alone. Based on the MyHPV chip results, the odds ratio (OR) for ≥ high-grade squamous intraepithelial lesions (HSILs) was 9.9 in the HPV-16/18 (+) group and 3.7 in the non-16/18 high-risk (HR)-HPV (+) group. Based on the HC2 results, the OR for ≥ HSILs was 5.9 in the HR-HPV (+) group. When considering only patients with cytological diagnoses of “negative for intraepithelial lesion or malignancy” and “atypical squamous cell or atypical glandular cell,” based on the MyHPV chip results, the ORs for ≥ HSILs were 6.8 and 11.7, respectively, in the HPV-16/18 (+) group. CONCLUSIONS: The sensitivity and specificity of the MyHPV chip test are similar to the HC2. Detecting HPV-16/18 with an HPV DNA chip test, which is commonly used in many Asian countries, is useful in assessing the risk of high-grade cervical lesions.
Asian Continental Ancestry Group ; Cervical Intraepithelial Neoplasia ; Diagnosis ; DNA* ; Epithelial Cells ; Human papillomavirus 16* ; Human papillomavirus 18* ; Humans ; Nucleic Acid Hybridization ; Odds Ratio ; Oligonucleotide Array Sequence Analysis* ; Risk Factors ; Sensitivity and Specificity ; Squamous Intraepithelial Lesions of the Cervix ; Uterine Cervical Neoplasms

OBJECTIVE: We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3). METHODS: Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013. RESULTS: The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; p<0.001). CONCLUSION: Our findings recommend the addition of high-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins.
Cervical Intraepithelial Neoplasia/pathology/surgery/*virology ; Female ; Humans ; Neoplasm Recurrence, Local/*virology ; Neoplasm, Residual ; Papillomaviridae/*isolation & purification ; Papillomavirus Infections/complications/*diagnosis ; Predictive Value of Tests ; Risk Assessment/methods ; Sensitivity and Specificity ; Uterine Cervical Neoplasms/pathology/surgery/*virology