Performance of a low cost magnifying device,magnivisualizer, versus colposcope for detection of pre-cancer and cancerous lesions of uterine cervix

Objective

To assess the performance of a low cost magnifying device (Magnivisualizer) compared to a standard optical colposcope for detection of precancerous and cancerous lesions of the uterine cervix.

Methods

A total of 659 consecutive symptomatic women attending a gynecologic outpatient clinic underwent unaided visual inspection followed by cytology, visual inspection of the cervix using 5% acetic acid (VIA), and VIA under magnification (VIAM) with the Magnivisualizer. All women, independently of test results, were referred for colposcopic examination. Colposcopic-directed biopsies were obtained from all positive lesions and compared to positive VIAM cases.

Results

The detection rate for VIA positive lesions was 12% (134/659), while it was 29% for VIAM positive lesions (191/659). The sensitivities of detection of cervical intraepithelial neoplasia (CIN) 2 and higher lesions were 61.7% for VIA, 88.3% for VIAM, and 86.7% for colposcopy, with a specificity of 58.5% for VIA, 55.8% for VIAM, and 90.4% for colposcopy. The performance of colposcopy and VIAM was moderate (κ, 0.48; 95% confidence interval [CI], 0.41 to 0.54) for detection of CIN 1 and higher lesions and excellent (κ, 0.87; 95% CI, 0.82 to 0.94) for detection of CIN 2 and higher lesions.

Conclusion

In low resource settings, where colposcopic facilities are not available at the community level, a simple low-cost, handheld Magnivisualizer can be considered a valid option for detection of cervical precancerous and cancerous lesions. However, it cannot replace traditional colposcopy because it has a low specificity that results in many unnecessary biopsies.     

Reflex Human Papillomavirus Test Results as an Option for the Management of Korean Women With Atypical Squamous Cells Cannot Exclude High‐Grade Squamous Intraepithelial Lesion

Background.

Current guidelines recommend initial colposcopy with biopsy regardless of human papillomavirus (HPV) test results in women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). The purpose of this study was to evaluate the value of HPV testing in women with ASC-H based on colposcopic pathology results.

Materials and Methods.

A multicenter cross-sectional study was carried out at three academic hospitals and involved 40,847 Korean women who underwent cervical cancer screening with cytology and HPV tests with or without subsequent colposcopic biopsies between January 2007 and December 2013.

Results.

ASC-H was diagnosed in 276 women (0.7%). Only 6 of 68 (8.8%) women with ASC-H who were HPV negative had cervical intraepithelial neoplasia grade ≥2 (CIN ≥2) lesions, whereas 47.4% of the women with ASC-H who were HPV positive had CIN ≥2 lesions. No cases of invasive cervical cancer were diagnosed among women with ASC-H who were HPV negative. Logistic regression analysis was performed using the group with normal Papanicolaou test results and HPV-negative status as the reference group. Women with ASC-H who were HPV positive had a significantly increased risk of CIN ≥2 lesions, whereas no significant increase was observed in patients with ASC-H and HPV-negative status.

Conclusion.

If the result of the HPV test was negative, the risk of CIN ≥2 lesions in Korean women with ASC-H cytology was low. Reflex HPV testing should be an option for the management of women with cytology showing ASC-H to decrease unnecessary colposcopic biopsies, which are expensive and invasive.

Implications for Practice:

Current American Society for Colposcopy and Cervical Pathology guidelines recommend universal colposcopy for the management of women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on cytology, regardless of human papillomavirus (HPV) test results. The present study suggested that HPV cotesting in patients with ASC-H cytology can provide more detailed and useful information regarding the risk of high-grade cervical intraepithelial neoplasia (CIN) lesions and the need for further treatment. When the result of the HPV test was negative, the risk of CIN lesions of grade ≥2 in women with ASC-H cytology was low. Consequently, reflex HPV testing, rather than immediately performance of invasive and expensive colposcopy with biopsy, should be an option for the management of women with ASC-H.     

Comparison of Hybrid capture 2 testing at different thresholds with cytology as primary cervical screening test

Background:

We evaluated the performance of primary high-risk human papillomavirus (hrHPV) testing by hybrid capture 2 (HC2) with different thresholds for positivity, in comparison with conventional cytology.

Methods:

We used data of 25 871 women (aged 30–60 years) from the intervention group of the VUSA-Screen study (VU University Medical Center and Saltro laboratory population-based cervical screening study), who were screened by cytology and hrHPV. Primary outcome measure was the number of cervical intraepithelial neoplasia grade 3 or higher (CIN3+), detected within 3 years. We compared baseline cytology testing with three possible hrHPV screening strategies at different relative light unit/cutoff (RLU/CO) thresholds.

Results:

Compared with baseline cytology testing, hrHPV DNA testing as a sole primary screening instrument did not yield a superior sensitivity, as well as lower colposcopy referral rate and lower false positivity rate at any RLU/CO threshold. The hrHPV screening at 1 RLU/CO threshold with cytology triage at baseline and at 12 months revealed the highest sensitivity for CIN3+ (relative sensitivity of 1.32), although still displaying a lower colposcopy referral rate than cytology testing (relative colposcopy rate of 0.94). Higher thresholds (>1RLU/CO) yielded lower colposcopy rates, but resulted in substantial loss in sensitivity.

Conclusions:

The hrHPV testing at the commonly used threshold of 1 RLU/CO with cytology triage at baseline and at 12 months showed a much higher sensitivity with a lower colposcopy referral rate compared with cytology testing.     

Primary cervical cancer screening with HPV testing compared with liquid-based cytology: results of round 1 of a randomised controlled trial �C 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.     

Effectiveness of two strategies to follow-up ASC-US and LSIL screening results in The Netherlands using repeat cytology with or without additional hrHPV testing: a retrospective cohort study

Purpose

The purpose of the study was to assess the effectiveness of repeat cytology with and without additional high-risk human papilloma virus (hrHPV) testing after atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (ASC-US/LSIL) screening results.

Methods

In the Netherlands, ASC-US/LSIL is triaged by repeat cytology at 6 months or repeat cytology at 6 months with additional hrHPV testing. ASC-US/LSIL results from 13,734 screenees in 2008 were extracted from “Dutch Pathology Registry” including cytology, histology, and/or HPV follow-up results. Proportions of compliance, repeat cytology, referral, and detected cervical intraepithelial neoplasia (CIN) were assessed.

Results

With additional hrHPV testing, 46.8 % was send back to regular screening at 6 months, 28.6 % needed second repeat cytology, and 24.6 % was referred for colposcopy. Without additional hrHPV testing, this was 0.0, 76.1, and 23.9 %, respectively. With additional hrHPV testing, significantly higher proportions of persisting ASC-US/LSIL; compliance with repeat/referral advices; and histological detection of CIN0 (no CIN or cancer), CIN1, and CIN2 were found but equal proportions CIN3+.

Conclusions

Additional hrHPV testing shortens follow-up without altering CIN3+ detection. Detection of CIN0, CIN1, and CIN2 was higher, presumably by hrHPV-driven biased cytology and detection bias. Restricting additional hrHPV testing to older women, reading cytology without knowledge of hrHPV status, and addition of more specific triage tests could further improve the effectiveness of additional hrHPV testing.     

Performance of HPV DNA Testing with Hybrid Capture 2 in Triaging Women with Minor Cervical Cytologic Abnormalities (ASC-US/LSIL) in Northern Thailand

Background: Minor cervical cytologic abnormalities include atypical squamous cells of undeterminedsignificance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL). Approximately 10-20% of womenwith minor cytologic abnormalities have histologic high-grade squamous intraepithelial or worse lesions (HSIL+).In Thailand, women with minor cytologic abnormalities have a relatively high risk of cervical cancer, and referralfor colposcopy has been suggested. A triage test is useful in the selection of women at risk for histologic HSIL+ toreduce the colposcopy burden. The aim of this study was to assess the performance of high-risk HPV DNA test intriage of women with minor cytologic abnormalities in northern Thailand. Materials and Methods: All womenwith ASC-US/LSIL cytology who were referred to our colposcopy clinic from October 2010 to February 2014were included. HPV DNA testing was performed using Hybrid Capture 2 (HC2). All patients received colposcopicexamination. Accuracy values of HC2 in predicting the presence of histologic HSIL+ were calculated. Results:There were 238 women in this study (121 ASC-US and 117 LSIL). The HC2 positivity rate was significantlyhigher in the LSIL group than in ASC-US group (74.8% versus 41.0%, p<0.001). Histologic HSIL+ was detectedin 9 women (7.4%) in the ASC-US group and 16 women (13.7%) in the LSIL group (p=0.141). There was nohistologic HSIL+ detected among HC2-negative cases (sensitivity and negative predictive value of 100%). Theperformance of HC2 triage was highest among women aged >50 years with ASC-US cytology. An increase in thecut-off threshold for positive HC2 resulted in a substantial decrease of sensitivity and negative predictive value.Conclusions: HPV DNA testing with HC2 shows very high sensitivity and negative predictive value in triage ofwomen with minor cervical cytologic abnormalities in northern Thailand. An increase of the cut-off thresholdfor HC2 triage is not recommended in this region.     

The Impact of Triage for Atypical Squamous Cells of Undetermined Significance with Human Papillomavirus Testing in Cervical Cancer Screening in Japan

Background: One of the features of cervical cancer screening using the combination of cytology and humanpapillomavirus (HPV) testing is the triage for atypical squamous cells of undetermined significance (ASC-US). Theeffectiveness of the triage has been recognized widely. However, there are few reports evaluating this triage process inJapan. Material and Methods: We retrospectively examined the results of cytology and HPV co-testing for cervicalcancer screening in the Oyama area of Tochigi Prefecture between 2012 and 2014. Women who were ASC-US/HPVpositive and had cytologic abnormalities [low-grade squamous intraepithelial lesions (LSIL) or worse] were examinedby colposcopy. The results of the colposcopy testing were evaluated. In addition, we also examined the results of thosewho underwent co-testing a year after a ASC-US/HPV-negative result. Results: A total of 21,342 women receivedtheir first screening test during the study period, with 542 (2.5%) found to have ASC-US. Of the ASC-US-positivewomen, 289 (53.3%) were also HPV positive. The prevalence of CIN+ (cervical intraepithelial neoplasia or higher)in the ASC-US/HPV-positive group was 63.2%, with 81.8%, 16.4% and 4.8%. showing CIN 1, CIN 2 and CIN 3+,respectively. The prevalence of CIN+ in the LSIL group was 66.8%, with the majority having a low risk CIN 1 (76.6%)compared to CIN 2 (18.6%), and CIN 3+ (4.8%). No significant difference was observed between the LSIL and ASC-US/HPV-positive groups. The prevalence of women diagnosed with CIN in the ASC-US/HPV-negative group, followingco-testing a year after colposcopy was low (3%). Conclusions: The ASC-US/HPV-positive group was comparable tothe LSIL group in terms of prevalence of CIN+ lesions. Furthermore, low CIN prevalence after one year in the ASCUS/HPV-negative group provides confirmation that the screening interval could be extended. The application of HPVtriage (which is routine in other countries) to identify these groups would be of benefit in Japan.     

Incomplete follow-up of positive HPV tests: overview of randomised controlled trials on primary cervical screening

Background:

It has been suggested that adjustment for incomplete compliance with follow-up in women with positive human papillomavirus (HPV) tests would be appropriate for estimating the true sensitivity of cervical screening with HPV testing. We assessed the compliance and its impact on ⩾CIN3 detection in all eight randomised controlled trials (RCT) with published baseline-round data.

Methods:

We extracted data on recommended follow-up procedures, follow-up compliance, and ⩾CIN3 detection for both arms of each RCT, and assessed their correlation.

Results:

Compliance with a direct referral for colposcopy was around 90% in all RCTs, whereas compliance with repeated testing among HPV-positive/cytology-negative women was around 60% in three RCTs and 73% in one RCT. Detection of ⩾CIN3 was significantly increased in two out of six RCTs with reported data. The correlation between compliance with follow-up in HPV-positive women and relative ⩾CIN3 detection was 0.48 (P=0.33).

Conclusion:

There is at present scant evidence to support the view that the measured sensitivity of HPV screening is a simple reflection of compliance with follow-up. Adjustment of measured cervical intraepithelial neoplasia detection on the basis of compliance data may not always be justifiable, and if adjustment is made, it should be used very judiciously.     

HPV immunisation and cervical screening—confirmation of changed performance of cytology as a screening test in immunised women: a retrospective population-based cohort study

Background:

To document the effect of bivalent HPV immunisation on cervical cytology as a screening test and assess the implications of any change, using a retrospective analysis of routinely collected data from the Scottish Cervical Screening Programme (SCSP).

Methods:

Data were extracted from the Scottish Cervical Call Recall System (SCCRS), the Scottish Population Register and the Scottish Index of Multiple Deprivation. A total of 95 876 cytology records with 2226 linked histology records from women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. The performance of cervical cytology as a screening test was evaluated using the key performance indicators used routinely in the English and Scottish Cervical Screening Programmes (NHSCSP and SCSP), and related to vaccination status.

Results:

Significant reductions in positive predictive value (16%) and abnormal predictive value (63%) for CIN2+ and the mean colposcopy score (18%) were observed. A significant increase (38%) in the number of women who had to be referred to colposcopy to detect one case of CIN2+ was shown. The negative predictive value of negative- or low-grade cytology for CIN2+ increased significantly (12%). Sensitivity and specificity, as used by the UK cervical screening programmes, were maintained.

Conclusions:

The lower incidence of disease in vaccinated women alters the key performance indicators of cervical cytology used to monitor the quality of the screening programme. These findings have implications for screening, colposcopy referral criteria, colposcopy practice and histology reporting.     

Evaluation of oncogenic human papillomavirus RNA and DNA tests with liquid-based cytology in primary cervical cancer screening: the FASE study

The APTIMA HPV Assay (AHPV) allows detection of 14 high-risk human papillomavirus (HPV) RNA types in cervical specimens. Until present, the assay has been compared to HPV DNA tests only in triage settings. Herein, we compare AHPV with a DNA assay (Hybrid Capture 2; HC2) and liquid-based cytology (LBC; using PreservCyt ThinPrep liquid Pap) in a screening setting (French APTIMA screening evaluation [FASE] study). Women (N = 5,006) aged 20-65 were screened by gynecologists in 17 private practices in Paris, France. One cervical specimen was collected and tested with LBC, AHPV and HC2 assays. Women were referred to colposcopy if they were ASC-US+ in LBC or HPV positive in either HPV assay. To control for verification bias, a random group (14%) with normal LBC and dually HPV negative tests underwent colposcopy. Data from 4,429 women were analyzed. Sensitivity, specificity and predictive values were calculated for the three tests. AHPV and HC2 were highly sensitive for CIN2+ (92.0% and 96.7%) and CIN3+ (95.7% and 95.3%) detection and much more sensitive than LBC (69.1% for CIN2+ and 73.3% for CIN3+). Specificity of AHPV was higher than that of HC2, but similar to that of LBC (p < 0.001). Combining LBC with either HPV test slightly increased sensitivity but compromised specificity. AHPV assay is both specific and sensitive for the detection of high-grade precancerous lesions and may be considered as an option for routine cervical cancer screening for women over 20 years of age.     

Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland

Background:

In Scotland, a national HPV immunisation programme began in 2008 for 12- to 13-year olds, with a catch-up campaign from 2008 to 2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established.

Methods:

We analysed colposcopy data from a cohort of women born between 1988 and 1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20–21 in 2008–2012.

Results:

By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1; RR 0.71, 95% CI 0.58 to 0.87; P=0.0008), CIN 2 (RR 0.5, 95% CI 0.4 to 0.63; P<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58; P<0.0001) for women who received three doses of vaccine compared with unvaccinated women.

Conclusions:

To our knowledge, this is one of the first studies to show a reduction of low- and high-grade CIN associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake.     

Type- and age-specific distribution of human papillomavirus in women attending cervical cancer screening in Finland

Background:

Large-scale data on type-specific HPV prevalences and disease burden are needed to monitor the impact of HPV vaccination and to plan for HPV-based cervical screening.

Methods:

33 043 women (aged 25–65) were screened for HPV by a Hybrid Capture 2 (HC2) in a population-based programme. HPV-positive women (n=2574) were triaged by cytology and HPV genotyped using PCR-Luminex. Type-specific prevalence of HPV infection and its correlation to findings in cytology triage and histology as well as Population Attributable Fractions for a referral to colposcopy and findings in histology were calculated.

Results:

Among HC2-positive women, 61.5% had normal, 23.1% had ASC-US and 15.5% had LSIL or more severe (LSIL+) results in cytology. Out of HC2-positive samples, 57% contained the 13 Group 1/2A HPV types, which were targeted by the HC2, 15% contained Group 2B types, 8.5% Group 3 types and 30% were found to be negative in HPV genotyping. The proportion of samples positive for HPV by the HC2, but negative in HPV genotyping increased with age and decreased with increasing cytological abnormality. The most frequent types were HPV 16 (0.9% of screened women and 12.1% of the HC2-positive women), HPV 31 (0.7% and 8.9%, respectively) and HPV 52 (0.5% and 6.3%, respectively). The prevalence of Group 1/2A HPV types increased with increasing CIN grade and attributed 78.3% (95% CI 53.4–89.9) of the CIN 3+ lesions, while HPV 16 attributed 55.8% (40.0–67.5) of them.

Conclusion:

The type-specific prevalence of HPV were slightly lower than the average in international meta-analyses. Genotyping for HPV 16 better identified women with CIN 3+ than cytology triage at the threshold of LSIL+. The high proportion of women that were HC2-positive but HPV-negative in genotyping suggests that HPV genotyping may be useful also for validation of results in HPV screening. The large-scale HPV genotyping data were found to be directly useful for planning further preventive efforts for cervical cancer.     

Early human papillomavirus testing predicts residual/recurrent disease after LEEP

Objective

The purpose of this study was to determine the predictive factors for residual/recurrent disease and to analyze the timing for Pap smears and human papillomavirus (HPV) testing during follow-up after loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 2 or worse.

Methods

We retrospectively analyzed 183 patients (mean age, 39.3 years) with CIN 2/3 who were treated with LEEP. Post-LEEP follow-up was performed by Pap smear and HPV hybrid capture2 (HC2) testing. The definition of persistent/recurrent disease was biopsy-proven CIN 2 or worse.

Results

Among 183 patients, punch biopsies were CIN 2 in 31 (16.9%) and CIN 3 in 152 (83.1%). HPV HC2 tests before LEEP were positive in 170 (95.5%) of 178 patients. During follow-up, 12 patients (6.6%) had residual/recurrent CIN 2+. LEEP margin status was a significant predictive factor for persistent/recurrent disease. Other factors such as age, HPV HC2 viral load (≥100 relative light units), and HPV typing (type 16/18 vs. other types) did not predict recurrence. Early HPV HC2 testing at 3 months after LEEP detected all cases of residual/recurrent disease. The sensitivity and negative predictive value of the HPV HC2 test for residual/recurrent disease were both 100% at 3 and 6 months.

Conclusion

Margin involvement in conization specimens was a significant factor predicting residual/recurrent disease after LEEP. HPV test results at 3 and 6 months after treatment were comparable. Early 3-month follow-up testing after LEEP can offer timely information about residual/recurrent disease and alleviate patient anxiety early about treatment failure.     

hr-HPV testing in the follow-up of women with cytological abnormalities and negative colposcopy

Background:

The follow-up after abnormal Pap smear and negative colposcopy is not clearly defined. This study aimed at investigating the role of hr-HPV testing in the management of abnormal Pap test and negative colposcopy for Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+).

Methods:

The study enroled 1029 women with abnormal screening cytology (years 2006–2010) and negative colposcopy for CIN2+, which subsequently performed a hr-HPV test. Incident CIN2+ lesions were identified through linkage with cancer registry, hospital discharge records, neoplastic pathology reports and the archive of screening programme (2006–2011).

Results:

During the follow-up, the cohort developed 133 CIN2+ lesions; only one among hr-HPV-negative women. The probability of developing CIN2+ on follow-up time was 0.44% (95% confidence interval (CI) 0.1–3.1) and 41.8% (95% CI 31.8–53.5) for hr-HPV-negative women and hr-HPV-positive women, respectively. A woman with a positive hr-HPV test had about 105 times higher probability of developing a CIN2+ lesion than a woman with a negative hr-HPV test (hazard ratio (HR)=104.5, 95% CI 14.5–755.1), adjusted for index Pap test result, age and cervix squamocolumnar junction visualisation.

Conclusion:

Our results confirm that hr-HPV testing is able to select the real group of women at risk of developing CIN2+ lesions in the follow-up of abnormal cytology and first negative colposcopy.     

Visual inspection with acetic acid for detection of high grade lesion in atypical squamous cells and low grade squamous intraepithelial lesions from cervical Pap smear

Objective

To evaluate the value of visual inspection with acetic acid (VIA) test to detect high grade lesion in women with atypical squamous cells or low grade squamous intraepithelial lesions cervical cytology.

Methods

Women with atypical squamous cells or low grade squamous intraepithelial lesions who were scheduled to undergo colposcopy at Vajira Hospital and met inclusion criteria were included. All participants underwent VIA test prior to usual steps of colposcopy. The VIA results were interpreted as positive or negative using the criteria by the International Agency for Cancer Research. The standard colposcopic examination and appropriate investigations for cervical pathology were then continued. The diagnostic values of VIA test including sensitivity, specificity, positive predictive value, and negative predictive value were determined using high grade lesion including cervical intraepithelial neoplasia 2-3 and squamous cell carcinoma as a threshold.

Results

Total of 106 women was included. The VIA test was positive in 33 women (31.1%) and negative in 73 women (68.9%). Among the women with VIA test positive, 14 had high grade lesion (42.4%) while 19 had no significant lesions. Only 2/73 (2.7%) cases with negative VIA test had high grade lesion (both had cervical intraepithelial neoplasia 2). The sensitivity, specificity, positive predictive value and negative predictive value with 95% confidence interval were 87.5% (81.2 to 93.8%), 78.8% (71.1 to 86.7%), 42.4% (33.0 to 51.8%), and 97.2% (94.2 to 1.0%) respectively.

Conclusion

VIA as the intermediate test in atypical squamous cells and low grade squamous intraepithelial lesions cytology may reduce the necessity to refer some women for colposcopy.     

HPV DNA testing in population-based cervical screening (VUSA-Screen study): results and implications

Background:

Human papillomavirus (HPV) testing is more sensitive than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN). We evaluated the performance of high-risk HPV (hrHPV) testing in routine screening.

Methods:

In all, 25 871 women (29–61) enrolled in our population-based cohort study were offered both cytology and hrHPV testing. High-risk HPV-positive women with normal cytology and an age-matched subcohort of hrHPV-negative women with normal cytology were invited for repeat testing after 1 and/or 2 years and were referred for colposcopy if they presented with abnormal cytology and/or a positive hrHPV test. The hrHPV-positive women with borderline or mild dyskaryosis (BMD) and all women with moderate dyskaryosis or worse (>BMD) were directly referred for colposcopy. Women with BMD and an hrHPV-negative test were advised to repeat cytology at 6 and 18 months and were referred for colposcopy if the repeat cytology test was abnormal. The main outcome measure was CIN grade 3 or worse (CIN3+). Results were adjusted for non-attendance at repeat testing.

Results:

The hrHPV-positive women with abnormal cytology had a CIN3+ risk of 42.2% (95% confidence interval (CI): 36.4–48.2), whereas the hrHPV-positive women with normal cytology had a much lower risk of 5.22% (95% CI: 3.72–7.91). In hrHPV-positive women with normal cytology, an additional cytology step after 1 year reduced the CIN3+ risk to only 1.6% (95% CI: 0.6–4.9) if the repeat test was normal. The CIN3+ risk in women with hrHPV-positive normal cytology was higher among women invited for the first time (29–33 years of age) (9.1% 95% CI: 5.6–14.3) than among older women (3.0% 95% CI: 1.5–5.5).

Conclusion:

Primary hrHPV screening with cytology triage in women aged ⩾30 years is an effective way to stratify women on CIN3+ risk and seems a feasible alternative to cytological screening. Repeat cytology after 1 year for hrHPV-positive women with normal cytology is however necessary before returning women to routine screening.     

Treatment of the patients with abnormal cervical cytology: a "see-and-treat" versus three-step strategy

Objective

To examine the correlation between cervical cytology and final histological results in patients who have undergone loop electrosurgical excision procedure (LEEP) with or without colposcopy-directed biopsy.

Methods

A retrospective review was performed of 829 patients who underwent LEEP for abnormal cervical cytology at Gangnam Severance Hospital between January 2004 and December 2008. Patients were classified to three groups according to cervical cytology and also divided into two groups based on the treatment they received: see-and-treat group and the standard three-step group. Final histological results were compared for the each study group.

Results

There were no differences in the final histological results between see-and-treat and three-step group in patients with high-grade squamous intraepithelial lesions (HSIL) cytology (N=523) (p=0.71). However, in patients with low-grade squamous intraepithelial lesions (LSIL)/atypical squamous cells of undetermined significance (ASCUS) (N=257) or normal cytology (N=49), the final histological results were significantly different between see-and-treat and three-step group (p<0.001) and the rate of overtreatment was significantly higher in the see-and-treat group (p<0.001).

Conclusion

A see-and-treat protocol may be a viable alternative only in patients with HSIL cytology if colposcopic impression is suggestive of cervical intraepithelial neoplasia (CIN) 2 or 3 lesions.     

Current status of the National Cancer Screening Program for cervical cancer in Korea, 2009

Objective

The National Cancer Screening Program (NCSP) began in 1999. In this report, we evaluate the results of the NCSP for cervical cancer in 2009 and provide participation rates in an organized cervical cancer screening program in Korea.

Methods

Using data obtained from the National Cancer Screening Information System, cervical cancer screening participation rates were calculated. Recall rates, defined as the proportion of abnormal cases among women screened, were also estimated with 95% confidence intervals.

Results

The target population of cervical cancer screening in 2009 included 4,577,200 Korean women aged 30 and over, 1,349,668 of whom underwent the Papanicolaou smear test (29.5% participation rate). Compared with the participation rate of women covered by the National Health Insurance Program (31.3%), the participation rate of women covered by the Medical Aid Program was lower (18.4%). Participation rates also varied in different age groups (the highest of 39.3% in women aged 50 to 59 and the lowest of 14.4% in those aged 70 and older), and different areas (the highest of 34.1% in Busan and the lowest of 21.5% in Chungnam). The overall recall rate for cervical cancer screening was 0.41% (95% confidence interval, 0.40 to 0.42).

Conclusion

According to our study, efforts to facilitate participation and reduce disparities in cervical cancer screening among Korean women are needed.     

Subsequent risks for cervical precancer and cancer in women with low-grade squamous intraepithelial lesions unconfirmed by colposcopy-directed biopsy: results from a multicenter, prospective, cohort study

Objective

To investigate the natural course of low-grade squamous intraepithelial lesions (LSILs) that cannot be histologically confirmed by colposcopy-directed biopsy.

Methods

In a multicenter, prospective, cohort study of Japanese women with LSILs, we analyzed the follow-up data from 64 women who had a negative biopsy result at the initial colposcopy (biopsy-negative LSIL) in comparison with those from 479 women who had a histologic diagnosis of cervical intraepithelial neoplasia grade 1 (LSIL/CIN1). Patients were monitored by cytology and colposcopy every 4?months for a mean follow-up period of 39.0?months, with cytologic regression defined as two consecutive negative smears and normal colposcopy.

Results

In women with biopsy-negative LSILs, there were no cases of CIN3 or worse (CIN3+) diagnosed within 2?years; the difference in the 2-year risk of CIN3+?between the two groups was marginally significant (0 vs. 5.5%; P?=?0.07). The cumulative probability of cytologic regression within 12?months was much higher in the biopsy-negative LSIL group (71.2 vs. 48.6%; P?=?0.0001). The percentage of women positive for high-risk human papillomaviruses (hrHPVs) was significantly lower in the biopsy-negative LSIL group than in the LSIL/CIN1 group (62.1 vs. 78.4%; P?=?0.01); however, the 12-month regression rate of biopsy-negative LSIL was similar between hrHPV-positive and -negative women (67.3 vs. 74.4%, P?=?0.73).

Conclusion

In women with biopsy-negative LSILs, the risk of CIN3+?diagnosed within 2?years was low; furthermore, approximately 70% underwent cytologic regression within 12?months, regardless of HPV testing results. Biopsy-negative LSILs may represent regressing lesions rather than lesions missed by colposcopy.     

The intra-nucleus integration of mitochondrial DNA (mtDNA)in cervical mucosa cells and its relation with c-myc expression

Objective

To explore the relationship between the integration of mitochondrial DNA(mtDNA) in the nuclei of cervical epithelium cells and the expression of c-myc.

Methods

The expression of c-myc protein was measured by immunohistochemical test in 40 cases of the uterine cervix cancer, 30 cases of cervical intraepithelial neoplasia (CIN) and 30 cases of normal cervical epithelium; the sequence of mtDNA in the nuclei was detected by in situ hybridization technique.

Results

The detection rates of mtDNA in the nuclei of cervical epithelium cells were 27.5%, 13.3% and 0% in cervical carcinoma, CIN, and normal cervical epithelium respectively. The expression rate of c-myc in cervical mucoma cells was 67% in the mtDNA sequence positive group and was significantly higher than that in the negative group (36%).

Conclusion

The integration of mtDNA into the nuclei of cervical epithelium cells may be involved in the carcinogenesis of cervical epithelium cells and the expression of c-myc might be related to the integration of mtDNA sequence into nuclei of cervical epithelium cells.