Atypical Squamous Cells Of Unknown Significance Research Articles

EsophaCap Sponge Cytology Screening for Esophageal Squamous Cell Dysplasia and Carcinoma is Feasible in a High-Risk Area in Western India

Objective: Conventional endoscopy remains the gold standard for detecting esophageal squamous cell carcinoma (ESCC) despite its high cost and need for expertise. In resource-poor regions, a less labor-intensive yet accurate screening tool is needed. The purpose of this study is to assess feasibility of establishing a non-endoscopic screening program in rural India and to test the diagnostic accuracy of the EsophaCap swallowable sponge in detecting ESCC in a high-risk patient population. Methods: A prospective cohort study was conducted between 2017 and 2019, in which subjects with risk factors for ESCC (tobacco smoking or chewing, betel nut/leaf, alcohol and hot beverage consumption) were approached during upper endoscopy visits at a clinic in Western India. After obtaining EsophaCap sponge cytology samples, random endoscopic biopsies were obtained at 20 and 30 cm from the incisors. Histologic diagnoses were confirmed and select biopsy samples were sequenced for genomic aberrations. Visual Analog Scale (VAS) scores were used to assess patient experience of sponge swallowing (range 1-5, “very comfortable” to “very uncomfortable”). Results: In our cohort of 178 patients, 157 (88%) were males. Mean age was 52 ± 12 years. Sixty-eight (38%) patients were current cigarette or bidi smokers; 132 (74%) patients were daily tobacco chewers, and 83 (47%) patients chewed betel nuts/leaves on a daily basis. Forty-six (26%) patients were daily alcohol users and 151 (85%) patients drank ≥3 hot beverages per day. The median number of risk factors per patient was 3. The first-time swallow rate of the encapsulated sponge was successful in 190/200 (95%) patients. Median VAS score was 2 (“comfortable”). EsophaCap cytology revealed 6 (3%) patients with atypical squamous cells of unknown significance (ASCUS) and 3 (1%) patients with dysplasia. Based on the endoscopic biopsies, 6 (3%) patients had ESCC, 4 (2%) patients had lesions with squamous dysplasia, and 63 (35%) patients had esophageal leukoplakia. Four patients classified as ASCUS pathology via EsophaCap were normal, benign, or leukoplakia via endoscopy. EsophaCap’s sensitivity and specificity for detecting dysplasia or ESCC by histology was 30% and 97%, respectively. Conclusions: Establishing a non-endoscopic screening program in a high-risk area with language barriers and low medical literacy is very safe and feasible. EsophaCap may help identify ASCUS patients in need of serial endoscopic monitoring. Further studies of combined sponge cytology with immunohistochemistry studies are necessary to improve accuracy of ESCC screening.

Frequency of abnormal Pap smear in patients presenting with postcoital bleeding in Tertiary Care Hospital, Karachi, Pakistan.

Postcoital bleeding increases the chance of detecting cervical dysplasia and cancer; and the Pap smear is the recommended screening test in these patients. We conducted a cross-sectional study that included 110 women to find out the frequency of abnormal Pap smear in such patients. Their age range was 15-65 years with a mean age of 31.2 ± 11.2 years. Abnormal Pap smear was found in 54 (49%) women. Atypical squamous cells of unknown significance (ASCUS) were found in 13.6%, low-grade squamous intraepithelial lesion (LSIL) in 20.9%, high-grade squamous intraepithelial lesion (HSIL) in 11.8% and carcinoma in 2.7% of those. Because of the high frequency of abnormal Pap smear associated with postcoital bleeding in our population, cervical screening and strict monitoring are suggested as the important screening indications.

LINE-1 and Alu Methylation in hrHPV-Associated Precancerous Cervical Samples.

This study was conducted to determine global DNA methylation patterns in cervical cells cytologically identified as atypical squamous cells of unknown significance (ASCUS) with a normal, LSIL, or HSIL histopathological result. Methylation patterns of long interspersed nuclear elements (LINE-1) and short interspersed element (Alu) sequences were assessed using the combined bisulfite restriction analysis (COBRA) method in cervical samples with cytology-diagnosed cervical lesions. In cervical precancerous lesions with hrHPV positive, the percentage of overall (mC) and mCmC LINE-1 methylation levels showed a stepwise increase from hrHPV positive normal to HSIL with significant differences (p<0.001). However, both methylation levels were significantly higher in hrHPV negative normal than in hrHPV positive normal (p<0.001). The overall (mC) Alu methylation in hrHPV positive LSIL and HSIL was lower than in hrHPV positive normal, with a significant difference (p<0.05). Remarkably, the percentage of uCmC and mCuC of LINE-1 and Alu in three different hrHPV positive cervical lesions showed a stepwise decrease from hrHPV positive normal, LSIL and HSIL, respectively. Furthermore, receiver operating characteristic (ROC) curve analyses revealed that the LINE-1 mC and mCmC patterns have high sensitivity and specificity for distinguishing HSIL from normal/LSIL in hrHPV positive cases at the appropriate cutoff levels. We have demonstrated the LINE-1 and Alu methylation data in normal and premalignant cervical epithelia. LINE-1 hypomethylation was found in hrHPV positive normal cells, with lower methylation levels associated with cancer features. In cytologically diagnosed Atypical Squamous Cells of Unknown Significance (ASCUS), the levels of mC and the mCmC pattern could be utilized in concert with hrHPV detection to classify the ASCUS sample prior to colposcopy.

Management of low-grade cervical cytology in young women. Cohort study from Denmark

Objective Cytology findings of atypical squamous cells of unknown significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) are common among women under 30, but evidence on best management strategy is insufficient. We therefore investigated how different management strategies used in Denmark influenced biopsy rates and detection of cervical intraepithelial neoplasia (CIN). Methods Register-based cohort study including Danish women aged less than 30 years and born 1980–95, with ASCUS/LSIL as their first abnormal cervical cytology in 2008–16. Rates and relative risks (RR) of biopsy and detection of CIN3+, CIN2 and < CIN2 during two years follow-up were compared between women referred directly to colposcopy after ASCUS/LSIL or undergoing additional testing, including mRNA or DNA test for high risk HPV or repeat cytology. Results 19,946 women with ASCUS and 19,825 with LSIL were included in the study of whom 92% had adequate information about follow-up. Among women referred directly to biopsy, CIN3+ was detected among 21%, CIN2 in 17%, while 62% had < CIN2. Repeating cytology after 6 months reduced the biopsy rate to 44% of which 53% had < CIN2. Biopsy rates with HPV test were 67% for DNA test, 77% with 14-type mRNA test and 58% with 5-type mRNA test. The detection of CIN3+ was somewhat higher, between 13% and 14% for the three HPV tests vs. 11% with repeat cytology. However, the detection of < CIN2 (not indicating treatment) also increased with RR 2.11 (95% CI 2.01–2.21) for 14-type mRNA test, 1.35 (95% CI 1.29–1.41) for 5-type mRNA test, and 1.86 (95% CI 1.76–1.97) with HPV DNA test. Conclusions The choice of management strategy influences both the detection rate for severe lesions (CIN3+) and the proportion of women followed up for potentially insignificant findings.

Utility of human papillomavirus L1 capsid protein and HPV test as prognostic markers for cervical intraepithelial neoplasia 2+ in women with persistent ASCUS /LSIL cervical cytology.

Objective: Efficient and highly predictive biomarkers reflecting the prognosis of persistent atypical squamous cells of unknown significance(ASCUS) and low grade squamous intraepithelial lesion(LSIL)s are unavailable and need to be developed urgently. We aimed to develop a predictive model for diagnosis of cervical intraepithelial neoplasia(CIN)2+ by analyzing the immunocytochemical expression of the HPV L1 capsid protein in patients with persistent ASCUS and LSIL with a high risk of HPV infection.Methods: Cervical cytology samples comprising (70 ASCUS and 215 LSIL Pap smears) were analyzed. Immunocytochemical identification of the HPV L1 capsid protein in cervical cytology samples was performed. Expression levels of HPV L1 capsid protein in cervical cytology samples were measured, and the correlation between HPV L1 expression and cervical pathologic diagnosis was evaluated. The risk for CIN2+ was calculated using the results of immunocytochemistry and the HPV DNA test.Results: Negative results for HPV L1 immunochemistry test were more frequently observed in CIN2+, and expression of the HPV L1 capsid protein was higher in CIN1 or cervicitis (Fisher's exact test, p<0.05). Diagnosis rates for CIN2+ were highest for the combination of HPV L1 capsid protein immunocytochemistry, cytology and HPV test when compared with other combinations (Akaike information criterion (AIC): 191.7, Schwarz criterion(SC): 206.3, p<0.001).Conclusion: Absence of HPV L1 capsid expression and presence of HPV type 16 or 18 infection are reliable predictors of progression to CIN2+ in patients showing persistent ASCUS and LSIL.

Quantification of HPV16 E6/E7 mRNA Spliced Isoforms Viral Load as a Novel Diagnostic Tool for Improving Cervical Cancer Screening.

High-risk human papillomaviruses (HPVs) have been identified as the main contributors to cervical cancer. Despite various diagnostic tools available, including the predominant Papanicolaou test (Pap test), technical limitations affect the efficiency of cervical cancer screening. The aim of this study was to evaluate the diagnostic performance of spliced HPV16 E6/E7 mRNA viral loads (VL) for grade 2 or higher cervical intraepithelial neoplasia diagnosis. A new dedicated (quantitative reverse transcription polymerase chain reaction) qRT-PCR assay was developed, allowing selective quantification of several HPV16 E6/E7 mRNA: Full length (FL) with or without all or selected spliced forms (total E6/E7 mRNA corresponding to SP + E6^E7 mRNA (T), + spliced E6/E7 mRNA containing intact E7 ORF (SP), and E6/E7 mRNA containing disrupted E6 and E7 ORFs calculated by the following subtraction T-SP (E6^E7)). Twenty HPV16 DNA and mRNA positive uterine cervical smears representative of all cytological and histological stages of severity were tested. We have shown that all E6/E7 mRNA isoforms expression levels were significantly increased in high grade cervical lesions. Statistical analysis demonstrated that the SP-E6/E7 VL assay exhibited: (i) The best diagnostic performance for identification of both cervical intraepithelial neoplasia (CIN)2+ (90% (56–100) sensitivity and specificity) and CIN3+ (100% (72–100) sensitivity and 79% (49–95) specificity) lesions; (ii) a greater sensitivity compared to the Pap test for CIN2+ lesions detection (80% (44–97)); (iii) a predictive value of the histological grade of cervical lesions in 67% of atypical squamous cells of unknown significance (ASC-US) and 100% of low-grade (LSIL) patients. Overall, these results highlight the value of SP-E6/E7 mRNA VL as an innovative tool for improving cervical cancer screening.

Systemic cervical cytology training and quality control programs can improve the interpretation of Papanicolaou tests

There is no national cervical screening program or national standards for cervical cytology quality control in China. Since 2013, systematic training and quality control programs were implemented in the Papanicolaou testing process at Jinan KingMed Diagnostics. Pathologists were required to complete 1 year of cytology study in the KingMed Diagnostics Cytology School, including 6 months of a diagnostic course and 6 months of practical training in the clinical laboratory. In this study, we compared the Papanicolaou abnormal reporting rates before and after the implementation systematic training and quality control programs. Systematic cytology training and quality control (QC) programs were implemented in 2013. Results from 997,162 cases of liquid-based cytology (LBC) and 100,066 cases of conventional Papanicolaou smears (CPS) rendered between 2008 and 2015 at Jinan KingMed Diagnostics were collected and analyzed. After implementation of training and programs, the abnormal reporting rates of atypical squamous cells of unknown significance (ASC-US), low-grade squamous intraepithelial lesions (LSIL), atypical squamous cells cannot exclude HSIL (ASC-H), atypical glandular cells (AGC), and high-grade squamous intraepithelial lesions (HSIL) in LBC were significantly increased. Similar trends were also observed in CPS reporting, except for ASC-H, squamous cell carcinoma, and AGC, probably due to the small percentages of these categories. The study demonstrates the importance of the formal cytology training and QC programs to ensure standardized and effective cervical cancer screening in undeveloped countries, which account for the largest percentage of the world's annual incidence of cervical cancer and with a largely unscreened population.

Differentiated cervical intraepithelial neoplasia-associated invasive cervical squamous cell carcinoma as a source of major cytopathological and surgical pathological discrepancy in Papanicolaou smear screening tests.

Differentiated cervical intraepithelial neoplasia (dCIN) analogous to differentiated squamous intraepithelial neoplasia of the vulva is characterised by the proliferation of atypical cells limited to the basal/parabasal layers. Exfoliative cytology of dCIN has not been investigated. A 46-year-old woman, with a history of normal Papanicolaou (Pap) smear up to 2years prior to the occurrence of postcoital vaginal bleeding had two consecutive Pap smears, which only revealed atypical squamous cells of unknown significance (ASCUS). The subsequent cervical biopsy revealed dCIN. The cone biopsy showed the invasive cervical squamous cell carcinoma (ICC) that developed from the overlying dCIN. Review of 32 consecutive cases of ICC revealed a second case of dCIN-associated ICC (Group 1) preceded by ASCUS suspicious for high-grade neoplastic cells. In both cases, the ASCUS were keratinised atypical cells without koilocytosis. In addition, there were another seven cases showing focal dCIN associated with extensive usual CIN (Group 2). In comparison with the remaining 24 cases with usual CIN (Group 3), Group 2 lesions occurred in younger patients (mean ages of 36±3 vs 47±9years) and were associated with shorter intervals after the last normal Pap smears. Pap smears in Group 2 occasionally consisted only of ASCUS cells. dCIN may occur in the cervix and accounts for a short interval of normal Pap smears and false negative or low-grade Pap smears in ICC.

ASC-US and LSIL triage in Korean women: Revisiting the 2012 ASCCP screening guidelines

Objectives: To examine whether the atypical squamous cells of unknown significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) triage of the updated American Society for Colposcopy and Cervical Pathology cervical cancer screening guideline is applicable in Korean women.

Manual liquid based cytology for Pap smear preparation and HPV detection by PCR in Pakistan.

This study was conducted on female patients with different gynecological problems attending the gynecology out-patient departments of two tertiary care hospitals in Peshawar city of Khyber Pakhtunkhwa, Pakistan between August 2012 and October 2013. The 200 patients had an age range of 21-65 years. Smears were taken with cervical brushes and preserved in preservative medium and processed for manual liquid based cytology (MLBC) for Pap staining. Out of 200 collected samples, 30 samples were found inadequate on cytology. Of the remaining 170 samples, 164 (96.47%) were normal, 5 (2.94%) were of atypical squamous cells of unknown significance (ASCUS) and 1 (0.6%) was of high grade squamous intraepithelial lesion (HSIL). On PCR all the samples were positive for beta globin gene fragment including those reported inadequate on cytology. Out of the 5 ASCUS samples, 2 samples were positive for HPV, one each for HPV 16 and HPV 18, and the rest of the 3 samples were negative for HPV DNA. The 1 sample of HSIL was positive for HPV 16 on PCR. Out of 164 normal samples on cytology, only 1 sample was HPV 16 positive. So overall, 4 (2%) out of 200 samples were positive for HPV DNA, where 3 were HPV 16 (1.5%), and 1 was HPV 18 (0.5%) positive, and thus the ratio of infection with of HPV 16 to HPV 18 was 3:1 in the general population. In conclusion, PCR based HPV detection is a more sensitive method for screening of HPV infection than cytology as sample inadequacy does not affect the results. However, it can be combined with cytology methods in a HPV positive female to achieve the maximum results.

Evaluation of 37,438 consecutive cervical smear results in the Turkish population.

IntroductionRetrospective evaluation of cervical smear results of women who attended our gynecology policlinics with various symptoms and discussion of the results in the light of the literature.Material and methodsWe performed a retrospective investigation on 37,438 Pap smear results of women who attended our hospital between January 2011 and December 2012 with a variety of symptoms.ResultsAverage patient age was 43 (18–83) years. Of the Pap smear results analyzed, in 21,503 (57.4%) findings were within normal limits, while 153 (0.41%) showed epithelial cell abnormalities and 15,358 (41%) showed inflammation. Four hundred and twenty-four (1.1%) cases were reported to have inadequate Pap smear samples for evaluation. Of the epithelial cell abnormalities, 136 (88.8%) were squamous cell abnormalities and 17 (11.1%) were glandular cell abnormalities. Atypical squamous cells of unknown significance (ASCUS) were reported for 117 (0.3%) Pap smears, while other epithelial abnormalities included atypical glandular cells of unknown significance (AGUS) in 17 (0.05%) cases, low-grade squamous intraepithelial lesion (LSIL) in 8 (0.02%) cases, atypical squamous cells with possible high grade lesion (ASC-H) in 8 (0.02%) cases and high-grade squamous intraepithelial lesion (HSIL) in 3 (0.008%) cases.ConclusionsPublic awareness should be raised on the importance of Pap smear testing repeated at appropriate intervals in the prevention and early diagnosis of cervical cancer. Health education should become more widespread, and the importance of screening programs and regular check-ups should be emphasized more often on this issue in the media.

Human papillomavirus testing 2007-2012: co-testing and triage utilization and impact on subsequent clinical management.

In the United States, high-risk human papillomavirus (HPV) testing is recommended for women with atypical squamous cells of unknown significance (ASC-US) cytology, and co-testing with cytology and HPV is a recommended option for screening women aged ≥ 30 years. No population-based data are available to examine utilization of HPV testing in the United States. Using the New Mexico HPV Pap Registry data resource, we describe population trends (2007-2012) in utilization and positivity rates for HPV testing as a routine co-testing screening procedure and for triage of ASC-US and other cytologic outcomes. For women aged 30-65 years co-testing increased from 5.2% in 2007 to 19.1% in 2012 (p < 0.001). Overall 82% of women with ASC-US cytology who did not receive co-testing also had an HPV test. HPV positivity was age and cytology result dependent but did not show time trends. For women with negative cytology, 64% received an additional screening test within 3 years if no co-test was done or if it was positive, but this was reduced to 47% with a negative co-test. Reflex HPV testing for ASC-US cytology is well established and occurs in most women. Evidence for reflex testing is also observed following other abnormal cytology outcomes. Co-testing in women aged 30-65 years has more than tripled from 2007 to 2012, but was still only used in 19.1% of women aged 30-65 years attending for screening in 2012. Women receiving co-testing had longer repeat screening intervals, but rescreening within 3 years is still very common even with co-testing.

Are There Flaws in the Follow-Up of Women With Low-Grade Cervical Dysplasia in Ontario?

BackgroundWhen cervical cytology screening shows atypical squamous cells of unknown significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL), and cervical cytology screening has not been performed in the previous year, it is recommended that cytology screening be repeated six months later. Women with persistent abnormalities should be referred for colposcopy. We explored provincial databases in Ontario to determine whether these recommendations were always followed. MethodsCervical cytology reports in Ontario are contained in a provincial database, deterministically linkable to other health services databases, including those recording physician reimbursement claims for colposcopy. We identified all women in Ontario who had a first time diagnosis of ASCUS or LSIL in 2008 or 2009. We searched for additional cytology reports and for colposcopy billing claims during the 24months following the date of the first abnormal report. We assessed the interaction of socioeconomic status, having abnormal cytology, and having repeat cytology after a report of low-grade abnormal cervical cytology. ResultsA total of 74 770 women had a first time report of low-grade abnormal cytology. Among women with ASCUS and LSIL, 69.7% and 60.3%, respectively, underwent repeat cytology. Repeat cytology following ASCUS disclosed normal (68.2%), ASCUS (19.3%), LSIL (10.6%), and high-grade squamous intraepithelial lesion (1.4%); following LSIL, the corresponding percentages were 48.3%, 18.0%, 30.8%, and 2.6%. Of women with ASCUS, 16.2% went directly for colposcopy; 14.0% did not repeat cytology or go for colposcopy. Of women with LSIL, 26.4% went directly for colposcopy but 13.4% had no follow-up. ConclusionWe have demonstrated the potential for substantial improvement in cervical cytology six months after a finding of ASCUS and LSIL. We found that many women with ASCUS and LSIL had unnecessary referrals directly for colposcopy, and we identified a lack of follow-up for one sixth of women with low-grade abnormal cytology.

Fluorescence In Situ Hybridization Testing for the Diagnosis of High-Grade Cervical Abnormalities

We examined the diagnostic performance of fluorescence in situ hybridization (FISH) tests on cervical cytology for precancerous lesions or cancer on cervical histology. A search was conducted in MEDLINE, the Cochrane Central Register of Controlled Trials, and Scopus through September 3, 2013. Eleven studies examined FISH tests for telomerase RNA component gene (TERC), myelocytomatosis oncogene (MYC), or human papillomavirus (HPV) type 16 or 18 in samples exhibiting atypical squamous cells of unknown significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). None examined HPV-positive, cytologically normal samples. We extracted data on the sensitivity and specificity for high-grade cervical intraepithelial neoplasia (CIN 2+ or CIN 3+). Fluorescence in situ hybridization test probes and thresholds varied across studies. Included populations were convenience samples. Only 1 study testing for TERC specified HPV status. In meta-analysis, FISH for TERC in LSIL (9 studies, 1,082 cases) had a summary sensitivity of 0.76 (95% confidence interval = 0.63-0.85) and a summary specificity of 0.78 (95% confidence interval = 0.57-0.91) for CIN 2+. Fluorescence in situ hybridization for TERC in ASC-US (3 studies, 839 cases) showed sensitivities ranging from 0.75 to 1.00 and specificities from 0.87 to 0.93 for CIN 2+. For CIN 3+, sensitivity and specificity appeared similar, although a small number of studies preclude firm conclusions. For FISH tests for HPV, we found only few studies with small sample sizes. The evidence on FISH testing is limited given the small number of studies for each cytology subgroup and the lack of studies in well-defined screening contexts stratifying participants by HPV status.

Current possibilities of cervical precancerous lesions screening in Slovakia: prevalence of highriskhuman papillomavirus in patients with cytological diagnoses of atypical squamous cells of unknown significance.

It has been confirmed, that there is a causal relationship between persistent infection of high risk human papillomavirus (HR-HPV) and the development of cervical cancer. In population of women older than 30 years HPV infection becomes a significant etiological factor of precancerous lesion of the cervix, but HPV infection may spontaneously regress in the majority of the cases. The analysed study group consisted of 397 samples with cytological diagnosis of atypical squamous cells of unknown significance (ASCUS). All cases underwent HPV DNA testing using the Hybrid Capture 2 (HC2) assay. We analysed prevalence of HR-HPV and a viral load expressed as relative light units/cut off ratio (RLU/CO) in different age groups with cytological diagnoses of ASCUS. The prevalence of HR-HPV with cytological diagnoses of ASCUS was detected in 44 %. The prevalence of HR-HPV between patients aged 17-29 and between patients aged 30-40 was 55 % and 48 % respectively and we detected significant reduction of prevalence (28 %) in patients older than 41 years. Based on the results of presented study we assumed that age the 40 and over is crucial for the development of serious precancerous lesions in Slovakia, thus this age group is the most suitable for HPV triage of ASCUS. As a refinement of that type of ASCUS triage we recommend to add to the algorithm quantitative measurement of viral load in the specimens in the form of RLU/CO ratio (Fig. 3, Ref. 27).

Clinicopathological Implications of Human Papilloma Virus (HPV) L1 Capsid Protein Immunoreactivity in HPV16-Positive Cervical Cytology

Background: The objective of this study was to investigate the expression of human papilloma virus (HPV) L1 capsid protein in abnormal cervical cytology with HPV16 infection and analyze its association with cervical histopathology in Korean women.Material and Methods: We performed immunocytochemistry for HPV L1 in 475 abnormal cervical cytology samples from patients with HPV16 infections using the Cytoactiv® HPV L1 screening set. We investigated the expression of HPV L1 in cervical cytology samples and compared it with the results of histopathological examination of surgical specimens.Results: Of a total of 475 cases, 188 (39.6%) were immunocytochemically positive and 287 (60.4%) negative for HPV L1. The immunocytochemical expression rates of HPV L1 in atypical squamous cells of unknown significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and cancer were 21.8%, 59.7%, 19.1%, and 0.0%, respectively. LSIL exhibited the highest rate of HPV L1 positivity. Of a total of 475 cases, the multiple-type HPV infection rate, including HPV16, in HPV L1-negative cytology samples was 27.5%, which was significantly higher than that in HPV L1-positive cytology samples (p = 0.037). The absence of HPV L1 expression in ASCUS and LSIL was significantly associated with high-grade (≥cervical intraepithelial neoplasia [CIN] 2) than low-grade (≤CIN1) histopathology diagnoses (p < 0.05), but was not significantly different between HPV16 single and multiple-type HPV infections (p > 0.05). On the other hand, among 188 HPV L1-positive cases, 30.6% of multiple-type HPV infections showed high-grade histopathology diagnoses (≥CIN3), significantly higher than the percentage of HPV16 single infections (8.6%) (p = 0.0004)Conclusions: Our study demonstrates that the expression of HPV L1 is low in advanced dysplasia. Furthermore, the absence of HPV L1 in HPV16-positive low-grade cytology (i.e., ASCUS and LSIL) is strongly associated with high-grade histopathology diagnoses. The multiplicity of HPV infections may have an important role in high-grade histopathology diagnoses (≥CIN3) in HPV L1-positive cases.

P3.233 Genital Tract Abnormalities in HIV-TB Co-Infected Women Initiating Antiretroviral Therapy (ART)

BackgroundHIV infected women have an increased risk of acquiring genital tract infections and progression of pre-malignant cervical lesions. We describe the prevalence and incidence of genital tract abnormalities in TB-HIV...

Could Alarmingly High Rates of Negative Diagnoses in Remote Rural Areas Be Minimized with Liquid-Based Cytology? Preliminary Results from the RODEO Study Team

Objective: It was the aim of this study to compare diagnostic performances of the BD SurePath™ liquid-based Papanicolaou test (LBC) and the conventional Papanicolaou test (CPT) in cervical samples of women from remote rural areas of Brazil. Study Design: Specimens were collected by mobile units provided by Barretos Cancer Hospital. This report evaluates the manual screening arm of the RODEO study. Of 12,048 women seen between May and December 2010, 6,001 were examined using LBC and 6,047 using CPT. Results: Comparative (LBC vs. CPT) outcomes were: all abnormal tests, 2.1 versus 1.0%; ASC-US (atypical squamous cells of unknown significance), 0.7 versus 0.1%; ASC-H (atypical squamous cells with possible high-grade squamous intraepithelial lesions) and AGC (atypical glandular cells), 0.4 versus 0.3%; LSIL (low-grade squamous intraepithelial lesions), 0.7 versus 0.3%; HSIL (high-grade squamous intraepithelial lesions), 0.4 versus 0.2%, and unsatisfactory, 0.03 versus 0.08%. The LBC arm detected significantly more lesions (ASC-US+) than CPT (p < 0.001); however, when we divided the diagnoses into two groups, ASC-H– (negative/ASC-US/LSIL) and ASC-H+ (ASC-H/AGC/HSIL), the difference was not statistically important (p = 0.213). Conclusions: With inherent difficulties in patient recruitment and patient compliance with cancer screening, best test performance including human papillomavirus test capability are vitally necessary in Brazil’s struggle to reduce cervical cancer.

Primary cervical cancer screening with HPV testing compared with liquid-based cytology: results of round 1 of a randomised controlled trial – the HPV FOCAL Study

Background:Round 1 data of human papillomavirus (HPV) FOCAL, a three-arm, randomised trial, which aims to establish the efficacy of HPV DNA testing as a primary screen for cervical cancer, are presented.Methods:The three arms are: Control arm – liquid based cytology with atypical squamous cells of unknown significance (ASC-US) triage with hrHPV testing; Intervention Arm – hrHPV at entry with liquid-based cytology (LBC) triage of hrHPV positives, with exit screen at 4 years; Safety check arm – hrHPV at entry with LBC triage of hrHPV positives with exit screen at 2 years.Results:A total of 6154 women were randomised to the control arm and 12 494 to the HPV arms (intervention and safety check). In the HPV arm, the baseline cervical intraepithelial neoplasia (CIN)2+ and CIN3+ rate was 9.2/1000 (95%CI; 7.4, 10.9) and 4.8/1000 (95%CI; 3.6, 6.1), which increased to 16.1/1000 (95%CI 13.2, 18.9) for CIN2+ and to 8.0/1000 (95%CI; 5.9, 10.0) for CIN3+ after subsequent screening of HPV-DNA-positive/cytology-negative women. Detection rate in the control arm remained unchanged after subsequent screening of ASC-US-positive/hrHPV DNA-negative women at 11.0/1000 for CIN2+ and 5.0/1000 for CIN3+.Conclusion:After subsequent screening of women who were either hrHPV positive/cytology negative or ASC-US positive/HPV negative, women randomised to the HPV arms had increased CIN2+ detection compared with women randomised to the cytology arm.

Prevalence and Determinants of High-risk Human Papillomavirus Infection in Women with High Socioeconomic Status in Seoul, Republic of Korea

We aimed to estimate the prevalence of high-risk human papillomavirus (HPV) infections in women of high socioeconomic status (SES) in Seoul, Republic of Korea and to identify risk factors. This study included 13,386 women visiting a prestigious healthcare center located in Seoul between 2003 and 2008. High-risk HPV infections were detected in 994 (7%) and the age-standardized prevalence was 8%. Abnormal Pap smear results ≥ atypical squamous cells of unknown significance (ASCUS) were observed in 280 of 12,080 women (2%). Based on univariate analysis, age, level of education and number of children were associated with high-risk HPV infections. Based on multivariate analysis, age and high-risk HPV infections had an inverse relationship. In women with high SES in Seoul, the prevalence of high-risk HPV infection was 7% and the age-standardized prevalence was 8%. Age was a strong determinant of high-risk HPV infection.