Initial Colposcopy Research Articles

Assessing Management of Abnormal Cervical Cancer Screening Results and Concordance with Guideline Recommendations in Three US Healthcare Settings.

Follow-up of abnormal results is essential to cervical cancer screening, but data on adherence to follow-up are limited. We describe patterns of follow-up after screening abnormalities and identify predictors of guideline-concordant follow-up. We identified the index screening abnormality (positive human papillomavirus test or atypical squamous cells of undetermined significance or more severe cytology) among women of ages 25 to 65 years at three US healthcare systems during 2010 to 2019. We estimated the cumulative incidence of surveillance testing, colposcopy, or treatment after the index abnormality and initial colposcopy. Logistic regressions were fit to identify predictors of guideline-concordant follow-up according to contemporaneous guidelines. Among 43,007 patients with an index abnormality, the cumulative incidence of any follow-up was 49.6% by 4 years for those with atypical squamous cells of undetermined significance/human papillomavirus-negative and higher for abnormalities warranting immediate colposcopy. The 1-year cumulative incidence of any follow-up after colposcopy was 70% for patients with normal results or cervical intraepithelial neoplasia I and 90% for patients with cervical intraepithelial neoplasia II+. Rates of concordant follow-up after screening and colposcopy were 52% and 47%, respectively. Discordant follow-up was associated with factors including age, race/ethnicity, overweight/obese body mass index, and specific types of public payor coverage or being uninsured. Adherence to the recommended follow-up of cytologic and histopathologic abnormalities is inconsistent in clinical practice. Concordance was poor for mild abnormalities and improved, although suboptimal, for more severe abnormalities. There remain gaps in the cervical cancer screening process in clinical practice. Further study is needed to understand the barriers to the appropriate management of cervical abnormalities.

Guideline adherent colposcopy completion following abnormal cervical cancer screening.

e17510 Background: Cervical cancer (CC) prevention relies upon timely management of abnormal screening results. Established recommended follow-up intervals for colposcopy after abnormal CC screening results exist for high-grade and low-grade abnormalities. Despite these guidelines, CC incidence is disproportionately higher in Black and Hispanic/Latino women in the US. Differential follow-up of abnormal screening results and delays in diagnosis may contribute to these disparities despite well-defined CC prevention measures. We investigated factors associated with guideline adherent colposcopy scheduling and attendance. Methods: Clinical and demographic medical record data was collected for patients with abnormal CC screening results from 2/2021 to 1/2022 at a large urban OB/GYN clinic in Connecticut. Timely colposcopy was defined as completion within 8 weeks from final CC screening result for high-grade abnormalities and 90 days for low-grade abnormalities. Clinical and demographic characteristics of patients needing colposcopy were examined. Association between these factors and completion of guideline adherent colposcopy was evaluated using univariate and multivariate regression. Colposcopy scheduling and attendance outcomes were compared by Pap grade using univariate regression and the Mann Whitney U test. Results: Overall, most of the 248 patients needing colposcopy identified as Black or Hispanic, spoke English, were publicly insured, had a low-grade Pap abnormality, and never smoked; half had received at least one dose of HPV vaccine. Among them, 215 (87%) received colposcopy ever and 190 (77%) received colposcopy within the guideline recommend interval. Race/ethnicity, preferred language, insurance status, pap grade, and smoking status were not significantly associated with receipt of timely colposcopy. In multivariate analysis only pregnancy was significantly associated with colposcopy receipt within the guideline recommended interval (RR=1.37, 95% CI: 1.11–1.69, p=0.004). There was no difference in receipt of colposcopy by pap grade. Scheduling of an initial colposcopy appointment was significantly lower among women with low-grade vs. high-grade CC screening abnormalities (94% vs. 100%, RR=1.03, 95% CI: 1.01–1.04, p<0.001). Patients with low-grade vs. high-grade abnormalities experienced similar numbers of no shows or cancellations for colposcopy appointments, with a maximum of 4 no shows or cancellations in each group. Conclusions: Evaluation of abnormal CC screening with colposcopy within guideline adherent time intervals can reduce diagnostic delays. Except for pregnancy, when there is increased interaction with healthcare, no other factors were associated with timely receipt of colposcopy. Further research on factors associated with receipt of colposcopy can contribute to implementation strategies to improve rates of timely follow-up for CC prevention.

Performance of standardised colposcopy to detect cervical precancer and cancer for triage of women testing positive for human papillomavirus: results from the ESTAMPA multicentric screening study

Colposcopy, currently included in WHO recommendations as an option to triage human papillomavirus (HPV)-positive women, remains as the reference standard to guide both biopsy for confirmation of cervical precancer and cancer and treatment approaches. We aim to evaluate the performance of colposcopy to detect cervical precancer and cancer for triage in HPV-positive women. This cross-sectional, multicentric screening study was conducted at 12 centres (including primary and secondary care centres, hospitals, laboratories, and universities) in Latin America (Argentina, Bolivia, Colombia, Costa Rica, Honduras, Mexico, Paraguay, Peru, and Uruguay). Eligible women were aged 30-64 years, sexually active, did not have a history of cervical cancer or treatment for cervical precancer or a hysterectomy, and were not planning to move outside of the study area. Women were screened with HPV DNA testing and cytology. HPV-positive women were referred to colposcopy using a standardised protocol, including biopsy collection of observed lesions, endocervical sampling for transformation zone (TZ) type 3, and treatment as needed. Women with initial normal colposcopy or no high-grade cervical lesions on histology (less than cervical intraepithelial neoplasia [CIN] grade 2) were recalled after 18 months for another HPV test to complete disease ascertainment; HPV-positive women were referred for a second colposcopy with biopsy and treatment as needed. Diagnostic accuracy of colposcopy was assessed by considering a positive test result when the colposcopic impression at the initial colposcopy was positive minor, positive major, or suspected cancer, and was considered negative otherwise. The main study outcome was histologically confirmed CIN3+ (defined as grade 3 or worse) detected at the initial visit or 18-month visit. Between Dec 12, 2012, and Dec 3, 2021, 42 502 women were recruited, and 5985 (14·1%) tested positive for HPV. 4499 participants with complete disease ascertainment and follow-up were included in the analysis, with a median age of 40·6 years (IQR 34·7-49·9). CIN3+ was detected in 669 (14·9%) of 4499 women at the initial visit or 18-month visit (3530 [78·5%] negative or CIN1, 300 [6·7%] CIN2, 616 [13·7%] CIN3, and 53 [1·2%] cancers). Sensitivity was 91·2% (95% CI 88·9-93·2) for CIN3+, whereas specificity was 50·1% (48·5-51·8) for less than CIN2 and 47·1% (45·5-48·7) for less than CIN3. Sensitivity for CIN3+ significantly decreased in older women (93·5% [95% CI 91·3-95·3] in those aged 30-49 years vs 77·6% [68·6-85·0] in those aged 50-65 years; p<0·0001), whereas specificity for less than CIN2 significantly increased (45·7% [43·8-47·6] vs 61·8% [58·7-64·8]; p<0·0001). Sensitivity for CIN3+ was also significantly lower in women with negative cytology than in those with abnormal cytology (p<0·0001). Colposcopy is accurate for CIN3+ detection in HPV-positive women. These results reflect ESTAMPA efforts in an 18-month follow-up strategy to maximise disease detection with an internationally validated clinical management protocol and regular training, including quality improvement practices. We showed that colposcopy can be optimised with proper standardisation to be used as triage in HPV-positive women. WHO; Pan American Health Organization; Union for International Cancer Control; National Cancer Institute (NCI); NCI Center for Global Health; National Agency for the Promotion of Research, Technological Development, and Innovation; NCI of Argentina and Colombia; Caja Costarricense de Seguro Social; National Council for Science and Technology of Paraguay; International Agency for Research on Cancer; and all local collaborative institutions.

Overtreatment rate after immediate local excision of suspected cervical intraepithelial neoplasia: A prospective cohort study

ObjectiveThe gold standard of cervical intraepithelial neoplasia (CIN) treatment is large loop excision of the transformation zone (LLETZ) after histopathological diagnosis from punch biopsies. In addition, treatment may be appropriate at initial colposcopy. Our objective was to study the applicability of immediate treatment strategy according to clinical parameters. MethodsWe conducted a prospective cohort study among patients referred to colposcopy at Helsinki University Hospital, Finland, between January 2014, and September 2018 (ISRCTN10933736). Patients treated with LLETZ, either after biopsies or immediately at initial colposcopy, were included. The main outcome measure was overtreatment (OT) rate defined as normal or low-grade histopathological findings in LLETZ specimen within both treatment groups. ResultsA total of 572 patients treated with LLETZ were included: 360 treated after biopsies and 212 treated immediately at initial colposcopy. When LLETZ was performed immediately after high-grade referral cytology and with colposcopic impression of high-grade disease, the overtreatment (OT) rate was 10.0% (95% CI 9.10 to 17.2), whereas when LLETZ was done after biopsy-confirmed high-grade lesions, the OT rate was 18.9% (95% CI 14.7 to 23.7), resulting in risk difference (RD) −8.91% (95% CI −16.0 to −1.82). Among HPV16/18 positive patients the OT rate was 8.22% (95% CI 3.08 to 17.0) for immediate treatment, resulting in RD of −10.7% (95% CI −18.3 to −3.04) compared to LLETZ after biopsies. ConclusionsImmediate LLETZ does not result in overtreatment when applied on selected cases, especially after high-grade referral cytology and when high-grade lesion is also colposcopically suspected.

Predictive Value of HPV E6/E7 mRNA Detection on the Outcome of Cervical LSIL.

Objective. To assess the predictive worth of HPV E6/E7 mRNA detection in the outcome of the cervical low-grade squamous intraepithelial lesion (LSIL). From September 2017 to early September 2019, patients screened for high-risk HPV positive or abnormal cervical liquid-based cytology were retrospectively analyzed and diagnosed with LSIL by cervical biopsy were recruited. The independent influencing factors of the regression of LSIL lesions after follow-up were analyzed, and the outcome of LSIL was calculated. The results of the initial colposcopy in this study were CIN I, CIN II/P16-negative, CIN II/P16-positive, and CIN III. At the time of re-examination, LSIL patients had three outcomes: regression, persistence, and progression. In the two follow-ups, 330 patients were finally included, including 276 CIN I patients (group A) and 54 CIN II/P16-negative patients (group B). The positive rates of HPV E6/E7 mRNA in each group were 66.67% and 70.37% for A and B, respectively. The total positive rate of E6/E7 mRNA was 67.27%, and there was no significant difference between the two groups (P > 0.05). After 1 year follow-up, whether HPV E6/E7 mRNA regressed or was negative was associated with the outcome of LSIL-related lesions (P < 0.05). The regression or negative rate of HPV E6/E7 mRNA was 1.57 times higher than the progression rate of HPV E6/E7 mRNA-positive diagnosis of LSIL lesions. Univariate logistic regression analysis showed that age at first sexual intercourse, HPV E6/E7 mRNA results, and lesion type were statistically significant (P < 0.05). Whether HPV E6/E7 mRNA was negative (OR = 2.420, P=0.001) and age at first sexual intercourse ≥20 years (OR = 0.420, P=0.002) were independent influencing factors associated with LSIL regression. Multivariate logistic analysis showed that age of first sexual intercourse ≥20 years (OR = 0.420, P=0.002) and HPV E6/E7 mRNA-negative (OR = 2.420, P=0.001) were independent factors associated with LSIL. HPV E6/E7 mRNA detection can be used for predicting the outcome of LSIL and has a good application value.

Are Women with Antecedent Low-Grade Cytology and

ObjectiveTo determine the baseline and cumulative risks of cervical intraepithelial lesion grade 3 (CIN3) and invasive cervical cancer in patients with <CIN2 colposcopy findings after a low-grade screening cytology finding (atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion [LSIL]). MethodsBy linking administrative databases, including cytology, pathology, cancer registries, and physician billing history, a population-based cohort study was performed on participants with <CIN2 initial colposcopy results after a low-grade antecedent cytology finding, between January 2012 and December 2013. Three and 5-year risks of CIN3 and invasive cervical cancer were generated using Kaplan-Meier survival analysis. ResultsAmong the 36 887 participants included in the study, CIN3 incidence based on referral cytology were as follows at 3 and 5 years, respectively: normal, 0.7% and 0.9%; ASCUS, 4.31% and 5.6%; and LSIL, 5.9% and 7.2%. Three- and 5-year incidence of invasive cancer were 0% and 0.02% for normal cytology, 0.08% and 0.11% for ASCUS, and 0.04% and 0.07% for LSIL, respectively. Stratifying risk by biopsy result at initial colposcopy, 3- and 5-year CIN3 incidences were 2.85% and 3.81% with a negative biopsy, 7.09% and 8.32% with an LSIL biopsy, and 4.11% and 5.2% when no biopsy was done, respectively. Three- and 5-year incidence of invasive cancer was 0% and 0.05% after a negative biopsy, 0% and 0% after LSIL biopsy, and 0.05% and 0.08% when no biopsy was done, respectively. ConclusionWhen initial colposcopy is done after a low-grade screening cytology result and <CIN2 is identified, the risk of CIN3 and invasive cancer is low, particularly when biopsies indicate LSIL. Surveillance strategies should balance the likelihood of detecting CIN3 with the potential harms over management with too frequent screening or colposcopic interventions in low-risk patients.

Devenir des femmes de moins de 30 ans prises en charge pour une lésion intra-épithéliale de haut grade du col utérin non traitée

ObjectivesTo assess the probability of spontaneous regression of high grade cervical intraepithelial neoplasia (HGCIN) in women under 30 and the predictive factors for such evolution. MethodsWe conducted a bicentric retrospective study. A total of 98 patients under 30 and with untreated HGCIN were included from 01/01/2010 to 31/12/2019. For each patient, the initial clinical and colposcopic characteristics were systematically documented. In compliance with French guidelines, these patients were offered repeated 6-months colposcopic follow-up for 2years. The endpoint was the occurrence of spontaneous regression of the HGCIN defined by normalization of colposcopy, and/or a negative biopsy and/or a negative HPV test or histological regression to low grade CIN, or a colposcopy showing simple minor abnormalities requiring no biopsy. ResultsSpontaneous HGCIN regression was observed in 37/98 patients. The median follow-up was of 16 (10.5–24.3) months. Predictive factors for spontaneous regression were: minor initial cytological abnormalities (HR=3.4; 95% CI: 1.02–11.05) and grade 1 atypical transformation at initial colposcopy (TAG1) (HR=2.3; 95% CI: 1.1–4.7). ConclusionBefore 30, the probability of spontaneous regression of HGCIN exists but remains low. Predictive factors for such evolution are minor initial cytological abnormalities and TAG1 colposcopic impression.

Predicting regression of cervical intraepithelial neoplasia grade 2 in women under 25 years

A number of retrospective and prospective studies have documented substantial rates of regression in cervical intraepithelial neoplasia grade 2 lesions in young women. Initial observational management of cervical intraepithelial neoplasia grade 2 is increasingly accepted as appropriate for women under 25 years of age with screen-detected abnormalities and is included in a number of clinical guidelines. However, there has been a paucity of large prospective studies on observational management with strict inclusion criteria. A number of important questions remain, specifically regarding the clinical variables that are associated with the risk of progression or persistence of disease. To investigate these factors and to ensure that young women with cervical intraepithelial neoplasia grade 2 undergoing observational management were being managed in a well-monitored and an appropriately informed fashion, we conducted a large, multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 in women under 25 years. This study aimed to determine the regression rates and clinical, cytologic, and pathologic predictors of regression of cervical intraepithelial neoplasia grade 2 in women under 25 years undergoing observational management over 24 months. This study was a multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 (ie, repeat colposcopy, cytology, and cervical biopsy every 6 months) for up to 24 months. A total of 615 consenting women under 25 years with newly-diagnosed, biopsy-proven cervical intraepithelial neoplasia grade 2 were recruited (from 2010 to 2016) through 16 hospital-based colposcopy units in New Zealand and Australia. At completion, 326 women had confirmed regression, 156 had persistent high-grade cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ, and 24 had unconfirmed regression (ie, first regression at the 24-month follow-up). A total of 109 women did not complete the protocol (41 because of delayed follow-up, 41 lost to follow-up, 22 elected treatment, 4 refused a biopsy, and 1 died of an unrelated cause). Confirmed regression was observed in 53% (326 of 615) of all women enrolled in the study and, when missing data were imputed, it was estimated that 64% of women (95% confidence interval, 60%-68%) would have experienced regression. Similarly, lesions regressed in 64% (326 of 506) of women who completed the observational protocol. Based on a multivariable analysis, detection of human papillomavirus 16 in a liquid-based cytology sample at the time of initial colposcopy decreased the chance of regression by 31% (risk ratio, 0.69; 95% confidence interval, 0.56-0.86; P<.001). In addition, at initial colposcopy, low-grade or normal colposcopic impression, later year of diagnosis, low-grade or normal cytology, and being a nonsmoker were all independently associated with an increased chance of regression. More than half of women under 25 years with cervical intraepithelial neoplasia grade 2 will regress to cervical intraepithelial neoplasia grade 1 or normal within 24 months without destructive treatment. The absence of human papillomavirus 16 is the most important predictor of regression.

Outcomes of women with positive oncogenic HPV and reflex cytology showing possible high-grade squamous intraepithelial lesion.

To examine outcomes in women following cervical screening detection of oncogenic human papillomavirus (HPV), with reflex cytology showing possible high-grade squamous intraepithelial lesion (pHSIL). A retrospective observational study of 523 women seen in the Royal Women's Hospital Colposcopy Clinic from 1 January 2018 to 31 July 2020. Two hundred eighty-two (53.9%) women had histology-confirmed HSIL, encompassing CIN2 or worse (CIN2+), including seven cancers (1.3%) and two adenocarcinoma in situ (AIS) (0.4%). In 81.2% (229/282) of women with CIN2+, this was detected on cervical biopsy at initial colposcopy, with another 8.9% (25/282) of CIN2+ detected at cervical excision following initial colposcopy and the remaining 9.9% (28/282) at follow-up colposcopy thereafter. When discordant cervical biopsy results were discussed at multidisciplinary meeting (MDM), 66.7% of women with pHSIL cytology upgraded to definite HSIL were found to have CIN2+, but only 20.8% when pHSIL cytology was retained and none when downgraded to low-grade (LSIL) or normal. No significant difference was found in the proportion of CIN2+ based on patient age above or below 40, HPV16 and/or 18 versus non 16/18, or whether discordant findings were reviewed at MDM. We propose a pathway for management of women with positive oncogenic HPV and reflex pHSIL cytology. MDM review is recommended when CIN2+ is not identified on cervical biopsy at initial colposcopy. Conservative management is safe with low risk of CIN2+ when LBC prediction of pHSIL is confirmed or downgraded at MDM with no high-grade change on colposcopy or repeat cytology.

Prevalence of High-grade Cervical Lesion (CIN 2+) in Thai Women with High Grade Squamous Intraepithelial Lesion Cytology

Background: The prevalence of high-grade cervical intraepithelial neoplasia (CIN2+), especially invasive cancer, among Thai women with high-grade squamous intraepithelial lesion (HSIL) cytology was reported higher than in Western populations. The aim of this study was to evaluate the prevalence of underlying significant cervical lesions (CIN2+) in women with HSIL cytology. Materials and Methods: A total of 4,487 women from the Woman Health Centre of Chulabhorn Hospital, Bangkok and 1,523 women from Bangkhayaeng District of Pathumthani province, Thailand, who participated in a cervical cancer screening program between July 2011 and August 2013, were recruited into the study. A total of 22 women (14 from Chulabhorn Hospital and 8 from Bangkhayaeng District) with HSIL cytology were recruited for colposcopic evaluations. Results: Of the 22 women with HSIL cytology, the median age was 42 years (22 to 67 years). The majority of patients were multiparous (90.9%) and premenopausal (72.7%). Final pathological results were as follows: 20 (91.0%) with CIN 2, CIN3 or adenocarcinoma in situ; 0 (0%) with CIN 1; 1 (4.5%) with no epithelial lesion; and 1 (4.5%) with cervical cancer. No clinical factors were associated with CIN2+. Conclusion: Rates of CIN 2+ at initial colposcopy following HSIL cytology in our population were very high (95.5%) and support the &ldquo;see-and-treat&rdquo; strategy for HSIL cytology management. Keywords: Prevalence, Cervical intraepithelial neoplasia (CIN), High-grade squamous intraepithelial lesion (HSIL), See and treat, Thailand

Prevalence of High-grade Cervical Lesion (CIN 2+) in Women with Low Grade Squamous Intraepithelial Lesion Cytology

Background: The frequency of high-grade cervical intraepithelial neoplasia (CIN2+) among Thai women with abnormal cytology, including low-grade squamous intraepithelial lesion (LSIL), was previously reported as higher than in Western populations. The aim of this study was to evaluate the prevalence of underlying significant cervical lesions (CIN2+) in women with LSIL cytology. Materials and Methods: A cross-sectional study was conducted among Thai women who participated in a screening program at the women&rsquo;s health clinic at Chulabhorn Hospital, Thailand, between July 2011 and August 2013. A total of 63 women with LSIL cytology were recruited for colposcopic evaluations. Results: A total of 63 women with LSIL smear were included; the median age was 38 years (22 to 67 years). Most women were multiparous (61.9%) and premenopausal (80.9%). After colposcopic evaluations, the histological results were as follows: 7 (11.1%) cases with CIN2, CIN3 or adenocarcinoma in situ; 18 (28.6%) with CIN1; 32 (66.7%) with no epithelial lesion; and no cases with cervical cancer. No clinical factors were found to correlate with high-grade cervical lesions. Conclusion: The rates of high-grade cervical lesion (CIN2+) at initial colposcopy following LSIL cytology in our population were lower than reported in previous studies. Keywords: Prevalence, Cervical intraepithelial neoplasia (CIN), Low-grade squamous intraepithelial lesion (LSIL), Thailand

Understanding the role of oncogenic human papillomavirus (HPV) status on adherence behaviors among women with abnormal cervical cytology

BackgroundWith the introduction of oncogenic Human Papillomavirus (HPV) testing into cervical screening there is a renewed focus on primary prevention among high-risk groups. To date, little is known about the effectiveness of this program, and the extent to which individual-level factors, such as psychosocial health and agency, may play a role. In particular, it is unclear if knowledge of one’s oncogenic HPV status impacts on adherence behaviors amongst women with screening abnormalities. The purpose of this study was to identify if clinical, demographic or psychosocial factors predict non-adherence with recommended colposcopy follow-up.MethodsThis prospective pilot study included 145 women referred to a large Toronto colposcopy clinic between December, 2013 and September, 2014. Demographic, clinical and psychosocial characteristics were collected at three points in time: (1) at initial colposcopy consultation; (2) 4–6 weeks following initial consultation, and; (3) at time of follow-up appointment (within 12 months of initial consultation).ResultsOverall, 13% (n = 145) of the women were classified as non-adherent. Older women (OR = 0.73, p < 0.01) and those with higher-grade lesions (OR = 0.10, p < 0.01) were less likely to be non-adherent, whereas current smokers (OR = 22.46, p < 0.01) were more likely to be non-adherent. While not statistically significant, variation in rates of non-adherence amongst the various HPV status groups (untested; 15.3%, HPV positive; 5.3%, HPV negative; 6.7%) warrants further study.ConclusionFindings of this study indicate that younger women, those with higher-grade lesions and current smokers were more likely to be non-adherent to recommended colposcopy follow-up. While HPV status did not reach statistical significance, the direction of this finding suggests that testing for HPV may have a positive reinforcing role on adherence to follow-up. The direction of this finding warrants further study, and potentially a practical clinical goal as HPV testing for women becomes standard of care.

Recurrent post-coital bleeding: Should colposcopy still be mandatory?

Colposcopy has been recommended for all women with recurrent post-coital bleeding (PCB) even if their cervical cytology or co-test (involving oncogenic human papillomavirus (HPV) DNA testing and cytology) are negative. To determine the risk of cervical cancer and its precursors among women with recurrent PCB with negative cytology or co-test. A retrospective analysis of two cohorts of women with PCB referred to a tertiary colposcopy clinic. Cohort (1) (n=1846) between 1 January 2000 and 31 December 2016 (cytology-based screening) and Cohort (2) (n=215) from 1 January 2018 to 31 December 2019 after introduction of primary HPV screening. In 1217 (65.9%) women in Cohort (1) referred with negative cytology, there was one cancer (0.08%) and 22 high-grade squamous intraepithelial lesions (HSIL (cervical intraepithelial neoplasia 2/3)) on histopathology. In Cohort (2), there was no cancer or HSIL in 83 women with negative co-tests (negative for oncogenic HPV and cytology). False-negative cytology after a negative referral cytology or co-test was low with 2% of repeat cytology at initial colposcopy showing possible HSIL or worse. Women presenting with PCB and negative cytology alone have a low risk of cancer and could have HPV testing before being triaged to colposcopy. We showed that with the assurance of a negative co-test and the low likelihood of false-negative cytology, these women could avoid colposcopy unless cervical cancer is clinically suspected. There is a need for a larger cohort study to substantiate our findings with more precision.

An audit of liquid-based cytology samples reported as high-risk human papillomavirus and borderline nuclear change in endocervical cells.

Primary human papillomavirus (HPV) screening, testing for the virus responsible for 99% of cervical cancers, was introduced in 2018-2020 in the UK. This was preceded by HPV triage of low-grade cytology from 2012. Much of the evidence incorporated into current National Health Service (NHS) colposcopy guidance assessed outcomes prior to this change in screening. The aim of this paper is to assess adherence to NHS cervical screening programme standards, determine the incidence of cases reported as high-risk HPV plus borderline nuclear change in endocervical cells, to calculate colposcopic accuracy and assess histological outcomes in this cohort. A retrospective audit of women referred to a colposcopy clinic in one NHS trust from 2016 to 2018. Data relating to histological outcomes, cytological follow-up and demographics were collected. Of 2001 referrals, 22 data sets identifying HPV-positive borderline endocervical change were eligible for analysis (1.2% incidence). Median age was 29.5. Two-thirds (68.2%, n = 15) had high-grade dysplasia at diagnostic biopsy. Those women with reassuring histology had normal cytological follow-up. Colposcopic accuracy was moderate (positive predictive value 43.8%, negative predictive value 100%). Borderline nuclear change in endocervical cells is an uncommon condition but should be treated as a high-grade referral. All women should be offered a diagnostic biopsy at the initial colposcopy; if no histopathological abnormality is identified, alternative sources of pathology should be considered. Excisional treatment should be recommended to unreliable attenders, those with a complete family and inadequate colposcopy (TZ3) and considered in younger women with a TZ3.

Risk of Cervical Dysplasia After Colposcopy Care and Risk-Informed Return to Population-Based Screening: A Systematic Review.

This systematic review examined the risk of cervical dysplasia among women who have undergone a colposcopy episode of care to inform their return to population-based cervical screening. PubMed, Embase, and grey literature were searched between January 2000 and 2018. One reviewer screened citations against pre-defined eligibility criteria. A second reviewer verified 10% and 100% of exclusions at title and abstract and at full-text screening, respectively. One reviewer extracted data and assessed methodological quality of included articles; a second reviewer verified these in full. The primary outcome was incidence of cervical intraepithelial neoplasia grade 2 or greater (CIN2+) subsequent to initial colposcopy evaluation. Secondary outcomes included incidence of CIN2+ after negative follow-up test results and performance of follow-up strategies. Results were synthesized narratively. A total of 48 studies were included. The 1- to 5-year CIN2+ risks after colposcopy evaluation ranged from 2.4% to 16.5% among women treated for CIN2+ and from 0.7% to 16.8% among women untreated for CIN grade 1 or less (≤CIN1). Follow-up strategies included single or repeat cytology, human papillomavirus (HPV) testing, or combined HPV/cytology co-testing at various intervals. After negative follow-up test results, risk varied by follow-up strategy for both groups and by referral cytology severity for untreated women. Performance of follow-up strategies varied among treated women. Among untreated women, co-testing demonstrated greater sensitivity than cytology alone. In conclusion, women treated during colposcopy for CIN2+ and women with ≤CIN1 who were referred to colposcopy for low-grade cytology and who did not receive treatment may be able to return to population-based screening after negative co-testing results. Current evidence does not suggest that women untreated for ≤CIN1 who are referred for high-grade cytology be returned to screening at an average risk interval. The optimal strategy for colposcopy discharge needs ongoing evaluation as implementation of HPV testing evolves.

MiRNA detection in cervical exfoliated cells for missed high-grade lesions in women with LSIL/CIN1 diagnosis after colposcopy-guided biopsy

BackgroundLow-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) preceded by colposcopy guided biopsy is recommended conservative follow-up, although some of these lesions are actually high-grade lesions, which are missed on an initial colposcopy. Therefore, in this work, we evaluate the potential role of miRNA detection in cervical exfoliated cells in a clinic-based population for predicting missed high-grade lesions in women diagnosed with LSIL/CIN1 after colposcopy-guided biopsy.MethodsA total number of 177 women with a diagnosis of LSIL/CIN1 obtained by colposcopy-guided biopsy were grouped into two categories according to the histology of the conization specimens: consistent LSIL/CIN1 group (surgical pathology consistent with colposcopic diagnosis) and missed high-grade lesion group (surgical pathology found high-grade lesion). The expression of eight miRNAs, such as miRNA195, miRNA424, miRNA375, miRNA218, miRNA34a, miRNA29a, miRNA16–2, and miRNA20a was detected by real time-quantitative polymerase chain reaction (RT-qPCR) in cervical exfoliated cells of the 177 patients. Pearson Chi-Square was used to compare the performance efficiency of patients’ characteristics. Nonparametric Man-Whitney U test was used to assess differences in miRNA expression. The receiver operating characteristic (ROC) curve was used to assess the performance of miRNA evaluation in detecting missed high-grade lesions.ResultsAmong the 177 women with biopsy-confirmed CIN1, 15.3% (27/177) had CIN2+ in the conization specimen (missed high-grade lesion group) and 84.7% (150/177) had CIN1-(consistent LSIL/CIN1 group). The relative expression of miRNA-195 and miRNA-29a in the missed high-grade lesion group was significantly lower than that in the consistent LSIL/CIN1 group. The relative expression of miRNA16–2 and miRNA20a in the missed high-grade lesion group was significantly higher than that in the consistent LSIL/CIN1 group. No significant difference was observed between these two groups regarding the other four miRNAs. Of these significant miRNAs, miRNA29a detection achieved the highest Youden index (0.733), sensitivity (92.6%), positive predictive value (46.2%), negative predictive value (98.3%) and higher specificity (80.7%) when identifying missed high-grade lesions.ConclusionsDetection of miRNA might provide a new triage for identifying a group at higher risk of missed high-grade lesions in women with colposcopy diagnosis of LSIL/CIN1.

Post-colposcopy Management of ASC-US and LSIL Pap Tests (PALS Trial): Pilot RCT.

Evidence supporting optimal follow-up of women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion cytology found to have low-grade disease or normal findings at initial colposcopy is weak. Surveillance options include continued colposcopy, discharge with Pap testing, or HPV testing at 12 months. This study was a pilot RCT comparing these three follow-up policies. The objectives were to determine the feasibility of an RCT and to compare the incidence of greater than or equal to high-grade squamous intraepithelial lesion (≥HSIL) in each of the follow-up policies. A total of 133 women referred with ASC-US or low-grade squamous intraepithelial lesion cytology between June and August 2012 underwent initial colposcopy where incident ≥HSIL histology was ruled out. Of these women, 125 were randomly assigned to colposcopic surveillance, Pap testing, or HPV testing. Patients with high-risk results at any point were treated according to standard of care. Patient recruitment and adherence to follow-up were calculated using descriptive statistics. Accuracy of the three follow-up arms was calculated (Canadian Task Force Classification: IC). Recruitment rates were 80%, and adherence to protocol was 85% to 100%. Nine of 125 (7.2%) patients overall were found to have ≥HSIL histology at exit: one of 43 in the reference colposcopy group, and six of 41 and three of 41 in Pap and HPV arms, respectively. One early cancer was detected in the HPV arm. Sensitivity and specificity (CI) for each arm, respectively, were as follows: colposcopy N/A, 100% (88.1%-100%); Pap, 100% (47.8%-100%) and 85.7% (63.7%-97%); and HPV, 66.7% (9.4%-99.2%) and 68% (46.5%-85.1%). This pilot study demonstrated the operational and safety feasibility of an RCT in this patient population. Validation of clinical findings is necessary.

A prospective study of risk-based colposcopy demonstrates improved detection of cervical precancers

Sensitivity for detection of precancers at colposcopy and reassurance provided by a negative colposcopy are in need of systematic study and improvement. We sought to evaluate whether selecting the appropriate women for multiple targeted cervical biopsies based on screening cytology, human papillomavirus testing, and colposcopic impression could improve accuracy and efficiency of cervical precancer detection. In all, 690 women aged 18-67 years referred to colposcopy subsequent to abnormal cervical cancer screening results were included in the study (ClinicalTrials.gov: NCT00339989). Up to 4 cervical biopsies were taken during colposcopy to evaluate the incremental benefit of multiple biopsies. Cervical cytology, human papillomavirus genotyping, and colposcopy impression were used to establish up to 24 different risk strata. Outcomes for the primary analysis were cervical precancers, which included p16+ cervical intraepithelial neoplasia 2 and all cervical intraepithelial neoplasia 3 that were detected by colposcopy-guided biopsy during the colposcopy visit. Later outcomes in women without cervical intraepithelial neoplasia 2+ at baseline were abstracted from electronic medical records. The risk of detecting precancer ranged from 2-82% across 24 strata based on colposcopy impression, cytology, and human papillomavirus genotyping. The risk of precancer in the lowest stratum increased only marginally with multiple biopsies. Women in the highest-risk strata had risks of precancer consistent with immediate treatment. In other risk strata, multiple biopsies substantially improved detection of cervical precancer. Among 361 women with cervical intraepithelial neoplasia <2 at baseline, 195 (54%) had follow-up cytology or histology data with a median follow-up time of 508 days. Lack of detection of precancer at initial colposcopy that included multiple biopsies predicted low risk of precancer during follow-up. Risk assessment at the colposcopy visit makes identification of cervical precancers more effective and efficient. Not finding precancer after a multiple-biopsy protocol provides high reassurance and allows releasing women back to regular screening.

Triaging Atypical Squamous Cells-Cannot Exclude High-Grade Squamous Intraepithelial Lesion With p16/Ki67 Dual Stain.

The management of women with Pap cytology results categorized as "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" (ASC-H) can often be challenging. We assessed the performance of p16/Ki67 dual-stained cytology as a potential triage tool for the detection of biopsy-confirmed high-grade squamous intraepithelial lesions (HSILs) in women with ASC-H. Women with ASC-H were followed for a period of 36 months by repeat cytology and colposcopy. p16/Ki67 dual staining was performed retrospectively on the initial Pap cytology slide with ASC-H interpretation. Results were compared with the final histological diagnosis and/or cytological follow-up for at least 1 year. All outcomes were defined as clinically significant at the threshold of HSIL (cervical intraepithelial neoplasia grade 2 or worse). One hundred sixty-nine cases fulfilled all conditions to be included in the study group. The rate of histologically confirmed HSIL was 57.4%, low-grade squamous intraepithelial lesion was diagnosed in 17.7% of the patients and normal histology or follow-up in 24.9% of the patients. Overall sensitivity and specificity of p16/Ki67 dual stain were 95% and 72%, respectively. Overall positive likelihood ratio of p16/Ki67 in detection of HSIL was 3.41, considerably increasing pretest probability from 57% to posttest probability of 82%. A substantial subset of patients with ASC-H interpretations is associated with an appreciable risk of clinically significant cervical disease. p16/Ki67 dual stain can provide additional valuable information that may lead to higher-quality management of women with ASC-H, especially when initial colposcopy or biopsy results do not show HSIL lesions.

Predictors of adherence to follow-up recommendations after an abnormal Pap smear among underserved inner-city women

ObjectivesThis study aimed to identify cognitive-affective predictors of adherence to initial diagnostic colposcopy and 6-month follow-up recommendations among underserved women. MethodsA secondary data analysis was completed of a randomized clinical trial assessing tailored telephone counseling for colposcopy adherence after an abnormal screening Pap smear among 210 underserved inner-city women. ResultsAdherence to initial diagnostic colposcopy was significantly associated with greater self-efficacy (OR=1.504, 95% CI 1.021–2.216). Women with lower monitoring attentional style had significantly greater adherence to 6-month follow-up recommendations compared to women with higher monitoring scores (OR=0.785, 95% CI 0.659–0.935). ConclusionIncreasing cervical cancer-related self-efficacy and tailoring cervical cancer risk communication to monitoring attentional style may help improve adherence to follow-up recommendations after an abnormal Pap smear test result. Practice implicationsFuture research is needed to develop and implement psychosocial approaches to improving adherence to diagnostic colposcopy and follow-up recommendations adherence among underserved women.