Abnormal Colposcopy Research Articles

Utility of colposcopy in a phase 2 portion of a microbicide clinical trial of BufferGel and 0.5% PRO 2000 Gel

BackgroundThe majority of new HIV infections are acquired through heterosexual transmission. There is urgent need for prevention methods to compliment behavior change and condom use. Topical microbicide represent a potential strategy for reduction of HIV transmission in women.MethodsMonthly Colposcopy evaluations were performed during pelvic examinations among 299 women enrolled in the Phase 2 portion of HPTN 035 study at four sites (1 in USA, 3 in Southern Africa). This was a phase 2/2b, multisite, randomized, and controlled clinical trial with four arms: BufferGel, 0.5% PRO2000 Gel, placebo gel and no gel. At two of the sites, pelvic examinations were conducted by the use of naked eye without colposcopy.ResultsA colposcopy finding of any kind was detected in 48% of participants at baseline compared to 40% at 3 months (p =0.04). The lower rates were also observed in vaginal discharge (22% at baseline, 16% at 3 months, p=0.06), erythema (15% at baseline, 8% at 3 months, p=0.004). The trend towards significance at p=0.05 disappear when utilizing stringent statistical significance levels. A pelvic finding of any kind was detected in 71% of colposcopy participants compared to 41% of participants who had naked eye examination only conducted at two sites that performed both colposcopy and naked eye without colposcopy. Use of colposcopy yielded significantly higher rates of participants with deep epithelial disruption, erythema and ecchymosis. We observed no cases of incident Chlamydia, Gonorrhea, or Syphilis during the three month follow up. There were 2 cases of incident HIV during 3-month study period neither of which was associated with any abnormal colposcopy evaluation findings.ConclusionNo safety signals were observed in the 4 study arms, allowing seamless transition from phase 2 to 2b. Colposcopy utility in microbicide clinical trials has minimal value given high rates of background noise findings of no relevant clinical significance.

Screening For Cervical Carcinoma By VIA

IntroductionCervical malignancy is amongst the most common malignancies that affect women. It has a long precancerous stage providing tremendous scope for early diagnosis and treatment. Though directed biopsy is the gold standard for diagnosis, and Papinacolou staining (Pap Smear) is currently the most effective screening method, both require an expensive and expertise demanding setup. In developing countries where such provisions are limited, an economical and easier effective alternative is desirable. Onesuch method is visual inspection of cervix with acetic acid (VIA Test). Study designOne year prospective study was carried out at Government Lalla Ded hospital Srinagar from June 2006 to May 2007 in which 1000 married, sexually active women attending gynecology OPD were screened for cervical disease using VIA as the screening tool. All women were further subjected to colposcopy and selected cases further underwent directed cervical biopsy. ResultsAmong the 1000 women screened, 170(17%) tested VIA positive. Most of these were from rural areas (87.6%), multipara (para3 and above were 91.7%) and of low socio-economic class (65.8%) with average age less than 20 years in (62.9%). From the VIA positive group 98(58%) women on further screening by colposcopy had abnormal findings as well and 72(42%) had no colposcopic findings.Women with abnormal colposcopy and positive VIA results were further evaluated with directed biopsy. 35(36%) out of 98 VIA and colposcopy positive women had abnormal histopathology findings on directed biopsy. ConclusionIna resource limited setting,VIA can be used as a good alternative for screening women for cervical cancer

Screening For Cervical Carcinoma By VIA

IntroductionCervical malignancy is amongst the most common malignancies that affect women. It has a long precancerous stage providing tremendous scope for early diagnosis and treatment. Though directed biopsy is the gold standard for diagnosis, and Papinacolou staining (Pap Smear) is currently the most effective screening method, both require an expensive and expertise demanding setup. In developing countries where such provisions are limited, an economical and easier effective alternative is desirable. Onesuch method is visual inspection of cervix with acetic acid (VIA Test). Study designOne year prospective study was carried out at Government Lalla Ded hospital Srinagar from June 2006 to May 2007 in which 1000 married, sexually active women attending gynecology OPD were screened for cervical disease using VIA as the screening tool. All women were further subjected to colposcopy and selected cases further underwent directed cervical biopsy. ResultsAmong the 1000 women screened, 170(17%) tested VIA positive. Most of these were from rural areas (87.6%), multipara (para3 and above were 91.7%) and of low socio-economic class (65.8%) with average age less than 20 years in (62.9%). From the VIA positive group 98(58%) women on further screening by colposcopy had abnormal findings as well and 72(42%) had no colposcopic findings.Women with abnormal colposcopy and positive VIA results were further evaluated with directed biopsy. 35(36%) out of 98 VIA and colposcopy positive women had abnormal histopathology findings on directed biopsy. ConclusionIna resource limited setting,VIA can be used as a good alternative for screening women for cervical cancer

Comparison of human papillomavirus testing and cytology for cervical cancer screening in a primary health care setting in the Democratic Republic of the Congo

ObjectivesWe compared the screening performance of conventional Pap cytology and two human papillomavirus (HPV) DNA assays, the original Hybrid Capture 2 (HC2) and an expanded version that tests for 4 additional HPV types (HC2+4; Qiagen Corporation), in the detection of cervical neoplasia among unscreened women in a primary care setting in a suburb of Kinshasa, Democratic Republic of the Congo. MethodsAll women 30years or older residing in the area were invited to participate, and 1528 were evaluated by Pap cytology and the two HPV assays, conducted at a European and US reference laboratory, respectively, followed by colposcopy. Cervical biopsies were obtained from all women with abnormal colposcopy and from 290 randomly chosen women with normal colposcopy (to correct for verification bias). ResultsUsing a relative light unit of 1 as the cutoff for positivity, 169 and 168 (11%) women tested positive using HC2 and HC2+4, respectively. HC2 and HC2+4 were in agreement in 98.6% of cases (Kappa=0.94; 95% confidence interval: 0.91–0.96). Both assays were sensitive (~83%) and specific (~91%) for the detection of cervical intraepithelial neoplasia-2 or worse disease. Irrespective of the cutoff point used to define positivity, Pap cytology was both less sensitive and more specific than HC2 or HC2+4. For instance, cytology was 63% sensitive and 97% specific when a cutoff point of low-grade squamous intraepithelial lesions or worse was used. ConclusionsAmong unscreened women, HC2 and HC2+4 had similar screening accuracy for cervical neoplasia, and both were more sensitive but less specific than Pap cytology.

Is Removal of Asymptomatic Cervical Polyps Necessary? Histologic Findings in Asymptomatic Israeli Jewish Women

: The purpose of the present study was to assess the frequency of abnormal histologic findings in polyps of asymptomatic Israeli Jewish women who are known to have a low incidence of cervical neoplasia. : The medical records of Israeli Jewish women with histologically proven cervical polyps treated during 2005 to 2009 in 2 Maccabi Health Service clinics that specialize in cervical pathology and colposcopy were retrieved from a computerized database. The records of asymptomatic women who underwent polypectomy were reviewed, and demographic information, clinical information, and the presence of abnormal colposcopic patterns, cervical intraepithelial neoplasia (CIN), and malignancy were abstracted. : The study included 228 asymptomatic women with cervical polyps who underwent colposcopy. Their median age was 49 ± 10.9 years (range = 21-82 y). The highest percentage of patients was observed in the 40- to 49-year-old age group, was Israeli-born, and was married. The percentage of patients referred because of an abnormal cytology report (29.4%) was considerably higher than the percentage reported in Israeli Jewish women. Abnormal colposcopy patterns were seen in 9 polyps, and CIN was found in 6 of them. Despite the high frequency of abnormal cytologic smears, CIN 3 was detected in only 1 polyp (0.4 %). In none of the polyps was malignancy found. : The very low frequency of neoplasia in cervical polyps of asymptomatic patients seems to support the notion that there is no clear indication for polypectomy when cytology is normal.

Role of high-risk human papillomavirus (HPV) mRNA testing in the prediction of residual disease after conisation for high-grade cervical intraepithelial neoplasia

ObjectiveTo evaluate testing for high-risk human papillomavirus (HR HPV) E6/E7 mRNA transcripts 6months after conisation for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) to determine the risk of residual CIN2+. MethodsWe prospectively followed 344 women treated for CIN2+ by conisation. HR HPV mRNA testing (PreTect HPV-Proofer, NorChip®), HR HPV DNA testing (AMPLICOR HPV Test, Roche Diagnostics®) and cytology was performed at 6 and 12months after conisation. Biopsies were taken within 18months of conisation if indicated by abnormal cytology, abnormal colposcopy, or positive HPV test. The LINEAR ARRAY HPV Genotyping Test (Roche Diagnostics®) was used to genotype cases with histologically confirmed residual disease diagnosed within 18months after conisation. Results6.4% (22/344) of study women had detected residual CIN2+. They were significantly older than those without residual CIN2+ (43.2 and 37.2years respectively, p<0.001). Among women with detected residual CIN2+, 54.5% (12/22) had positive resection margins, 63.6% (14/22) had abnormal cytology, and 95.5% (21/22) had a positive HR HPV DNA test at 6months. Sensitivity of HR HPV mRNA testing was 45.5% (95% confidence interval: 26.8-65.5%) at 6months to predict detected residual CIN2+. Eight of 12 women who were HR HPV mRNA-negative at 6months were HR HPV DNA-positive for one of the HPV types included in the mRNA test. ConclusionDetection of E6/E7 mRNA transcripts by PreTect HPV Proofer does not seem suitable for short-term follow-up to detect residual CIN2+ after conisation.

Value of HPV-DNA test in women with cytological diagnosis of atypical glandular cells (AGC)

ObjectiveThis study analyzed whether HPV (human papillomavirus) testing contributes towards defining histological abnormalities in women with atypical glandular cells (AGC) diagnosed at cervical cytology. Study designOne hundred and eight women with conventional cervical cancer screening smears suggestive of AGC not otherwise specified (AGC-NOS) and favor neoplastic (AGC-FN) were consecutively enrolled. All women underwent colposcopic examinations and biopsy was performed according to the cytopathologic and/or colposcopic abnormalities present. All specimens were tested for high risk HPV genotypes by Roche's polymerase chain reaction reverse line blot assay. The chi-square test was used to evaluate the association between HPV findings and a diagnosis of high-grade pre-invasive or invasive disease (CIN 2 or worse) taking negative tests or CIN 1 as a reference. Odds ratios (OR) with their respective 95% confidence intervals (95%CI) were used to evaluate the magnitude of the association between HPV testing and CIN 2 or worse. Sensitivity, specificity and their respective 95% confidence intervals (95%CI), positive predictive values (PPV) and negative predictive values (NPV) were also calculated. ResultsFinal diagnosis revealed a negative outcome in 80 cases (74%), cervical epithelial neoplasia 1 (CIN 1) in 13 cases (12%), CIN 2 or worse in 12 cases (11%) and glandular neoplasia in 3 (3%) cases. The overall detection rate of HPV was 21% (23/108). Neoplasia was significantly associated with positive HPV-DNA in women with AGC-NOS (OR=15.21; 95%CI: 2.64–87.50); however, there was no significant association between a histological diagnosis of neoplasia and HPV positivity in women with AGC-FN (OR=3.00; 95%CI: 0.36–24.92). The sensitivity, specificity, positive predictive value and negative predictive value of HPV-DNA testing for the detection of CIN 2 or worse in women with AGC-NOS were 71%, 86%, 29% and 97%, respectively. In women with AGC-FN, these values were 50%, 75%, 66% and 60%, respectively. ConclusionsHPV testing at the time of colposcopy for patients with AGC in whom no colposcopic abnormality is found may be a powerful ancillary tool for identifying women at a high risk of underlying significant cervical lesions.

Efficacy of the ASO4-adjuvanted HPV-16/18 vaccine in reduction of abnormal cytology, colposcopy referrals and cervical excision therapies: PATRICIA end-of-study results

Efficacy of the ASO4-adjuvanted HPV-16/18 vaccine in reduction of abnormal cytology, colposcopy referrals and cervical excision therapies: PATRICIA end-of-study results

Human Papillomavirus Testing in the Prevention of Cervical Cancer

Strong evidence now supports the adoption of cervical cancer prevention strategies that explicitly focus on persistent infection with the causal agent, human papillomavirus (HPV). To inform an evidence-based transition to a new public health approach for cervical cancer screening, we summarize the natural history and cervical carcinogenicity of HPV and discuss the promise and uncertainties of currently available screening methods. New HPV infections acquired at any age are virtually always benign, but persistent infections with one of approximately 12 carcinogenic HPV types explain virtually all cases of cervical cancer. In the absence of an overtly persistent HPV infection, the risk of cervical cancer is extremely low. Thus, HPV test results predict the risk of cervical cancer and its precursors (cervical intraepithelial neoplasia grade 3) better and longer than cytological or colposcopic abnormalities, which are signs of HPV infection. The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening. A major challenge will be implementing programs that do not overtreat HPV-positive women who do not have obvious long-term persistence of HPV or treatable lesions at the time of initial evaluation. The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment.

Invasive Cervical Cancer Audit: Why Cancers Developed in a High-Risk Population With an Organized Screening Programme

In the United Kingdom, routine screening of all women for cervical cancer is conducted at defined intervals (3 or 5 years). Interval cervical Neoplasias have been diagnosed during the screening interval preceding diagnosis, and some of these are invasive cancers. It is unclear whether the cancers were diagnosed as a result of the investigation of symptoms or investigation of an abnormal cytology test during routine screening in asymptomatic women. The primary aim of this observational study was to investigate why invasive cervical interval cancers developed in a high-risk urban population with an established screening program, to look for reasons why they were not prevented, and for preventable causes. Precancerous cervical intraepithelial neoplasia CIN2 + CGIN, CIN2, CIN3 lesions and invasive cervical cancers were diagnosed at Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in 1999-2001, 2002-2004, and 2005-2007. The NHS Screening program audit of screening histories of all women diagnosed with invasive cervical cancer provided data on route to diagnosis, histological type, and International Federation of Obstetrics and Gynecology stage. A period of 5 years was chosen to define interval cancers. During the 9-year study period, 133 invasive cervical cancers were diagnosed, and there were 1472 biopsy diagnoses of CIN2, 1502 diagnoses of CIN3, and 53 diagnoses of CGIN. About 49% of the cancers identified were screen-detected cancers in asymptomatic women; these were successively more likely to occur in younger age groups (P = 0.03), and with one exception, all were stage IA or IB1. Screen-detected IA cancers were significantly more likely (P < 0.001) to be interval cancers (80.5%) than screen-detected fully invasive cancers (58.3%) or symptomatic cancers (35.5%). Cytology tests had been performed in routine screening during the 5 years before diagnosis in 53.4% (71/133) of all cancers. Among these 71, negative cytology had been reported within 5 years of diagnosis in 11 women who had been screened within 3.5 years and 2 women had negative tests within 10 years. Negative tests had occurred less frequently in the other 60 women, or they had previous abnormal cytology, colposcopy, or treatment. A number of potentially avoidable factors were identified, including false-negative cytology, high-grade cytology misidentified as low-grade, and poor compliance in attendance either for routine or repeat screening or for colposcopy or treatment. These findings show that interval cancers diagnosed in previously screened women tend to be early-stage tumors detected by cytology, which are rare in comparison with high-grade CIN and often are potentially avoidable.

Invasive cervical cancer audit: why cancers developed in a high‐risk population with an organised screening programme

Please cite this paper as: Herbert A, Anshu, Culora G, Dunsmore H, Gupta S, Holdsworth G, Kubba A, McLean E, Sim J, Raju K. Invasive cervical cancer audit: why cancers developed in a high‐risk population with an organised screening programme. BJOG 2010;Objectives To investigate why invasive cervical cancers developed in a high‐risk urban population with an established screening programme and to place cancers in the context of high‐grade cervical intraepithelial neoplasia (CIN) and cervical glandular intraepithelial neoplasia (CGIN) diagnosed during the same period of time.Study design Observational study of CIN2+ (CGIN, CIN3 and CIN2) and invasive cervical cancer diagnosed at Guy’s and St Thomas’ NHS Foundation Trust in 1999–01, 2002–04 and 2005–07 and audit of screening histories of women with invasive cancer analysed according to route to diagnosis, histological type and International Federation of Obstetrics and Gynecology (FIGO) stage.Results There were 133 invasive cancers, 53 CGIN, 1502 CIN3 and 1472 CIN2. Screen‐detected cancers in asymptomatic women comprised 48.9% of cancers and were successively more likely to be in younger age groups (P = 0.03); all except one were stage IA or IB1. Screen‐detected IA cancers were more likely (P &lt; 0.001) to be in women screened within 0.5–5.0 years (80.5%) than screen‐detected fully invasive (58.3%) or symptomatic cancers (35.3%). Seventy‐one (53.4%) women had been screened within 0.5–5.0 years; 11 had negative cytology within 0.5–3.5 years and two tests within 10 years. The other 60 had negative tests less frequently or had previous abnormal cytology, colposcopy or treatment. Potentially avoidable factors were often multiple, including false‐negative cytology, high‐grade cytology reported as low‐grade and lapses in attendance either for routine or repeat screening, or for colposcopy or treatment.Conclusion While often potentially avoidable, cancers in previously screened women tended to be early stage, detected by cytology and rare when compared with high‐grade CIN.

Hybrid capture vs. PCR screening of cervical human papilloma virus infections. Cytological and histological associations in 1270 women

BackgroundWe evaluated two molecular methods of HPV detection and their correlation with cytological and histological diagnosis in a large sample of Greek women.MethodsAll women with liquid-based cytology performed at a University Hospital between 2000 and 2003 were included. The Hybrid Capture 2 (HC2) kit and in house Polymerase Chain Reaction (PCR) were used for HPV DNA detection. Cervical biopsy was performed for women with ASCUS+ cytology, HPV detection, or abnormal colposcopy. Positive (PLR) and negative (NLR) likelihood ratios were calculated for cytology and HPV molecular testing for the prediction of CIN2 and greater histology.ResultsOf the 1270 women evaluated 241 (18.5%) had abnormal cytology. Cytology diagnosed high-grade squamous intraepithelial lesion (HSIL) or invasive carcinoma in 21(1.7%) cases whereas 26 (2%) women had CIN2+ or greater histology. PCR detected HPV in 397/1270 (31.3%) and HC2 in 260/1270 (20.4%) samples. Both molecular tests exhibited high reproducibility (Cohen's kappa value 0.691, 95% CI: 0.664 - 0.718). Positive likelihood ratios (PLR) of 9.4, 3.8 and 3.4 and negative likelihood ratios of 0.13, 0.21, and 0 were noted for ≥ LSIL, any positive HC2 or any positive PCR-HPV testing, for predicting CIN2+ histology, respectively. All CIN 3+ lesions harbored high risk oncogenic HPV type infections.ConclusionsHPV infection was found in a large proportion of this population and was associated with CIN 2/3 lesions and infiltrating carcinomas. Thin prep testing and HPV detection by HC2 or PCR performed very well with regards to identifying high grade lesions in an environment with experienced examiners.

Evaluation of cervical visual inspection screening in Dar es Salaam, Tanzania

Objective To evaluate the feasibility and performance of screening for cervical cancer using visual inspection with acetic acid (VIA) or with Lugol's iodine (VILI) in Dar es Salaam, Tanzania. Methods The accuracy of tests for detecting cervical intraepithelial neoplasia (CIN) was assessed in a cross-sectional study of 10 378 women. All women who were screened underwent colposcopy, and biopsies were offered to those with abnormal colposcopy results. Results The positivity rates were 3.8% for VIA and 4.8% for VILI. The peak positivity rates for both visual tests were observed just after training or re-training and gradually declined thereafter. CIN 1 was diagnosed in 41 women, CIN 2–3 in 33 women, and invasive cancer in 200 women, showing high detection rates of invasive cancer. The sensitivity and specificity for the detection of CIN 2–3 lesions were 60.6% (95% confidence interval [CI], 42.1–77.1) and 98.2% (95% CI, 97.9–98.4), respectively, for VIA; and 93.9% (95% CI, 79.8–99.3) and 97.3% (95% CI, 97.0–97.6), respectively, for VILI. Two-thirds of the women detected with CIN 2–3 lesions were treated. Conclusion Both visual screening tests are useful and accurate, especially in low-income settings. Standardization of assessment of the visual inspection techniques, continual training and supervision, and quality control measures are important for successful visual screening programs.

Follow-up Compliance of Adolescents with Cervical Dysplasia in an Inner-city Population

Study Objective Adolescent compliance with cytologic and histologic cervical abnormalities is poor. Recent changes in abnormal cytology follow-up and colposcopy indications in young women may delay the diagnosis of cervical dysplasia. The objective of our study was to determine the compliance with follow up. We also wanted to summarize regression or progression of disease, and to determine if the new guidelines could affect severity and time of diagnosis. Design Retrospective review of medical records from adolescent patients (defined as women aged 12 to 21) who had a colposcopy between January 2004 and December 2006. Patients were excluded if they were 22 or older or if they had a previously abnormal cytologic evaluation. Main Outcome Measures Colposcopy records between January 2004 and December 2006 were identified by CPT code from a computerized database. Cytology and histology results, follow-up compliance rates, and demographic data were collected. Data were analyzed with a power > 85% and a P value ≤ .05 for significance. Results Of the 210 records reviewed, 61.9% had atypical squamous cells of undetermined significance high-risk HPV, 33.7% had low-grade squamous intraepithelial lesion, and 4.5% had high-grade squamous intraepithelial lesions. Colposcopy was performed in 55.9%, and 15.2% required surgical intervention. Loop electrosurgical excision procedure (LEEP) was used in 87.5% of patients, and 12.5% had a cold knife cone. Mean time to follow in patients with a surgical intervention was 12.72 months and 11.02 months for those without ( P = .371). Conclusion There appears to be no difference in compliance with follow-up, regardless of severity of disease or surgical intervention. There was no significant progression of disease and a high regression rate of abnormalities. This information supports the current American College of Obstetricians and Gynecologists and American Society for Colposcopy and Cervical Pathology guidelines to delay aggressive intervention in adolescents.

Performance of colposcopy in five sub‐Saharan African countries

The performance of colposcopy provided in a screening study in five African countries was evaluated. Cross-sectional study. Burkina Faso, Congo Brazzaville, Guinea Conakry, Mali and Niger. Women aged 25-59 years. A total of 29 294 women participated in a cervical screening study in the five study sites, and newly trained local doctors performed colposcopy and directed biopsies as indicated. Using meta-analytical tools, four measures of colposcopy performance at different thresholds of colposcopic abnormalities were assessed. Sources of heterogeneity were also assessed. Proportions of women receiving biopsies, adequate biopsies and women diagnosed with cervical intraepithelial neoplasia (CIN). Among 28 553 women with satisfactory colposcopy, 3101 had a colposcopic diagnosis of probable low-grade or worse lesions and 1128 probable high-grade or worse lesions. Overall, the measures that reached the set standards were proportion of biopsy taken at colposcopy threshold of probable high-grade or worse lesions (95%, 95% CI 90-100%) and proportion of adequate biopsy samples. The set standards were not met for the proportions of women diagnosed with CIN at different colposcopic abnormality thresholds. Detection of CIN2 or worse lesions increased with increasing colposcopic abnormality. The performance of colposcopy in some of the African sites studied was comparable to that previously observed in other studies. With appropriate training, monitoring, continuing practice and quality assurance, adequate standards of colposcopy can be attained in sub-Saharan Africa.

Prediction of Human Papillomavirus 16 E6 Gene Expression and Cervical Intraepithelial Neoplasia Progression by Methylation Status

Human papillomavirus (HPV) infection represents the most important risk factor for the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. We aimed to analyze the consequences of methylation of the E6 gene promoter in distinct stages of HPV-16-induced cellular transformation to assess its importance for disease progression. Human papillomavirus 16 was detected by sensitive polymerase chain reaction (PCR). Determination of E6 gene promoter methylation was analyzed by digestion with specific restriction endonuclease McrBC followed by PCR amplification. Expression of the E6 gene was determined by quantitative real-time PCR. Of 103 cervical smears from asymptomatic women with no cytological and colposcopic abnormalities, 20.4% were HPV-16-positive. Human papillomavirus 16 was present in 44.4% of 18 patients with CIN I, in 62.2% of 143 patients with CIN II/III, and in 74.2% of 31 cervix carcinoma specimens. The incidence of HPV-16 in all lesions compared with asymptomatic women was statistically significant (P < 0.001, Pearson chi test). Methylation was detected in 81% (n = 21) of HPV-16-positive asymptomatic smears compared with 62.5% in CIN I (n = 8), 31.5% (n = 89) in CIN II/III, and 43.4% (n = 23) in carcinomas; a statistical significance between lesions and healthy women was found (P < 0.001, Pearson chi test). Expression of E6 mRNA correlated with methylation status (P = 0.010, Mann-Whitney U test). We conclude that methylation of the E6 gene promoter in HPV-16 genome is a predictive biomarker for cervical cancer progression by regulating the expression of the E6 oncogene.

Identification of vaccine human papillomavirus genotypes in squamous intraepithelial lesions (CIN2–3)

Objective To identify the prevalence of human papillomavirus vaccine genotypes and non-vaccine genotypes implicated in the appearance of cervical intraepithelial neoplasia (CIN2–3). Methods Prospective study of 519 women with abnormal cytology. All the women underwent a second Papanicolaou test, cervicovaginal sampling for type-specific HPV detection and colposcopy, and women with abnormal colposcopy results were referred to biopsy. Pearson's chi-square test was used for statistical analysis. Results HPV was detected in 340 patients (65.5%), and in 125 (24%) more than one HPV genotype was present. We selected 206 patients with CIN2 or CIN3 confirmed by biopsy. In 88 (42.7%) of these patients, HPV types 16 and 18 were detected, but only 58 (28.2%) without co-infection by other high-risk or probable high-risk HPV types. In 115 (55.8%) women diagnosed with CIN2 or CIN3 high-risk or probable high-risk HPV types other than 16 or 18 were found. High-risk and/or probable high-risk HPV genotypes not included in the vaccine were isolated in this study more frequently than 16 or 18, and this difference was statistically significant ( p = 0.047). Of the 206 women diagnosed with CIN2 or CIN3, 19 tested negative for HPV and 14 tested positive for low-risk HPV types. Conclusion Only 28.2% of women with CIN2 or CIN3 confirmed by biopsy were infected exclusively by HPV type 16 or 18, a finding that places in doubt the degree of protection afforded by HPV vaccination.

Linear array genotyping and hybrid capture II assay in detecting human papillomavirus genotypes in women referred for colposcopy due to abnormal Papanicolaou smear

The main objective of this study was to assess the feasibility of human papillomavirus (HPV) genotyping in women referred for colposcopy due to abnormal Papanicolaou (Pap) smear. A series of 248 women referred for colposcopy due to an abnormal Pap smear were analysed with the Roche Linear Array HPV genotyping test detecting 37 most frequent HPV types, and compared with hybrid capture II (HCII) assay for oncogenic (high-risk [HR] HPV) types as well as for p16INK4a expression using immunocytochemistry. All tests were performed in cervical samples collected in PreservCyt liquid media for liquid-based cytology (ThinPrep), and colposcopic biopsy and/or loop electro excision procedure cone biopsy was used as the gold standard. HPV16 was the single most frequent genotype (29/258; 11.7%), followed by HPV51 (4.4%), HPV66 (3.6%), HPV42, 52 and 56 (3.2% for all). Linear array genotyping test significantly predicts both abnormal colposcopy (odds ratio [OR] = 9.0; 3.12-25.93), high-grade squamous intraepithelial lesions (OR = 9.6; 1.26-74.17) and cervical intraepithelial neoplasia (CIN) 3+ (OR = 29.3; 3.95-218.06). In detecting CIN3, linear array was equivalent (97.6%) to colposcopy in sensitivity (SE), both being superior to HCII (92.7%). Concordance between linear array and HCII was moderate (Cohen's kappa kappa = 0.547; 95% confidence interval [CI]: 0.435-659). Specificity (SP) and positive predictive value (PPV) of linear array were significantly improved, if only HPV16 genotype was considered. Performance in the best balance is obtained, when linear array and colposcopy are combined, giving 82.9% SE, 93.9% SP, 73.9% PPV and 96.3% negative predictive value (NPV) as predictor of CIN3+ (OR 74.5; 95% CI: 27.36-202.72). In conclusion, linear array for HR-HPV is a highly sensitive test (97.6%) with high NPV (98.9%) in detecting CIN3+ lesions. HPV16 genotyping alone significantly improves SP and PPV of this test in management of women with abnormal cytology.

Impact of colposcopy on management outcomes of patients with abnormal cervical cytology

With stringent cervical cytology screening programmes for women in reproductive age group, cervical cancer is, to a large extent, preventable. Back-up confirmatory colposcopic evaluation is necessary in order for cytology to have impact on cervical cancer-related morbidity and mortality. To track the management outcomes of abnormal cervical cytology and hence confer credence to the value of colposcopy in management of abnormal cervical cytology. Retrospective descriptive study. Kenya Medical Women Association Colposcopy Clinic. Correlation of cervical cytologic abnormalities with colposcopic outcomes and eventual management outcomes. The population was young, with 50.6% being 25-34 years old, and 59.3% less than 35 years of age. Parity was also low, with nearly 75% being para three or less. A substantial proportion of women had normal colposcopic findings (42.0, 26.7,18.6 and 11.1% for cytologic abnormalities CIN I, CIN II, CIN III and invasive carcinoma respectively). Colposcopic abnormality detection rate, irrespective of the severity of the lesion, increased with severity of cytologic lesion (from 58.0% CIN I to 89.0% for invasive carcinoma). The sensitivity of cervical cytology was 58, 59 and 65% for CIN I,II and III respectively, while respective specificity was 72, 71 and 85%. The concordance rates between cytological and colposcopic findings were 38.6, 32.5 and 60% for CIN I, II and III respectively. The eventual management outcome was operative (LEEP and Hysterectomy) in greater frequency as the severity of the cytologic lesion increased. Colposcopy has significant impact on the management outcomes of abnormal cervical cytology and is therefore an invaluable procedure in management of abnormal cervical cytology. For this reason, it is imperative that governments avail these services to all women, in addition to enforcing regular cytologic screening for cervical cancer.

Abnormal cervicovaginal cytology with negative human papillomavirus testing

Human papillomavirus (HPV) testing has become part of cervicovaginal diagnostics in many laboratories. False-negative HPV results, even if rare, are potentially relevant clinically, particularly when testing is used alone. In this study, the authors investigated the occurrence and causes of abnormal cervicovaginal cytologies with negative HPV testing. The study was performed on 4130 liquid-based cytology (LBC) specimens from 2918 women who had abnormal cervical cytology or colposcopy or a history of abnormal cervical smear. HPV testing with Hybrid Capture II was repeated in LBC specimens with obviously atypical cytology (squamous intraepithelial lesion or abnormal squamous cells, cannot exclude high-grade lesion) and initial negative test results. The results were compared with the follow-up results and with the cytologic features of the specimens. Of 4130 LBC specimens, 94 (2.28%) showed obviously abnormal cells despite negative HPV results, and 50 of those 94 samples (53.19%) were HPV-positive on a repeated testing of the same specimen. Histologic follow-up showed high-grade intraepithelial lesion or carcinoma in 10 specimens that initially were negative for HPV. Eight of those samples were HPV-positive on testing repetition. Both specimens that had persistently negative results had poor-quality cytologic samples at revision. High-grade lesions may be identified in the follow-up of HPV-negative specimens with abnormal cytology. Testing repetition in patients with discordant cytology may prevent most potentially clinically relevant false-negative HPV results.