The role of cervical cytology and colposcopy in detecting cervical glandular neoplasia

Objective:  To determine the role of cervical cytology and colposcopy in the management of endocervical neoplasia.
Setting:  Colposcopy unit and cytology laboratory in a teaching hospital.
Sample:  Group 1 included 184 smears showing endocervical glandular neoplasia from 129 patients and group 2 included 101 patients with histology showing endocervical abnormalities in a 6-year period (1993–1998). Follow-up of 6–11 years to 2004 was available.
Methods:  Group 1 were identified from the cytology computer records. Group 2 were identified from histology records on the cytology database and a record of histology cases kept for audit purposes. The clinical records were examined retrospectively.
Results:  The positive predictive value (PPV) of abnormal endocervical cells in smears was 81.1% for significant glandular/squamous [cervical glandular intraepithelial neoplasia (CGIN)/cervical intraepithelial neoplasia grade2 (CIN2 or worse)] lesions. The PPV of colposcopy was 93.5% for significant glandular/squamous lesions of the cervix. The postcolposcopy probability of a significant lesion when colposcopy was normal was 87.5%. The sensitivity of colposcopy in detecting endocervical lesions was 9.8%. The sensitivity of cervical smears in detecting a significant endocervical abnormality (CGIN or worse) was 66.3%. The false negative rate for cytology of endocervical glandular lesions was 4.0%.
Conclusions:  Endocervical glandular neoplasia detected on cytology is predictive of significant cervical pathology even when colposcopy is normal, which supports excisional biopsy in the primary assessment of these smears. The high concomitant squamous abnormality rate justifies the use of colposcopy to direct biopsies from the ectocervix. Cervical cytology is the only current screening method for cervical glandular abnormalities but sensitivity is poor.     

Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology

A. Talaat, D. Brinkmann, J. Dhundee, Y. Hana, J. Bevan, R. Irvine, S. Bailey and R. Woolas
Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology Objective: To review the risk of pre‐invasive and invasive gynaecological pathology in women referred with cervical cytology reporting ?glandular neoplasia. Methods: Review of the case notes of all women referred with cervical cytology reported as ?glandular neoplasia between January 1999 and December 2008 at two UK hospitals: Portsmouth Hospitals NHS Trust and Queen Mary’s Hospital Sidcup. The category of ‘borderline nuclear change in endocervical cells’, result code 8 according to the national health service cancer screening programme (NHSCSP), was excluded from the study. Results: A total of 200 women were identified using the hospitals’ pathology computer systems. Invasive carcinoma was found in 48 women (24%): 28 endocervical adenocarcinomas, eight squamous cell carcinomas (SCC), ten endometrial and two ovarian adenocarcinomas. Pre‐invasive neoplasia was found in 115 (57.5%), including 14 cervical glandular intraepithelial neoplasia (CGIN), 31 cervical intraepithelial neoplasia (CIN) grade 2/3 and 70 concomitant CGIN and CIN2/3. CIN1/HPV was found in 25, simple endometrial hyperplasia in three and no histological abnormality in three. Thirty‐four (70.8%) of 48 invasive carcinomas (of which 23 were endocervical adenocarcinomas) were in asymptomatic women investigated for abnormal cytology. Fourteen of 34 (41.4%) of those with ?glandular neoplasia thought to be endometrial were CGIN or CIN2/3. Colposcopic appearances were normal in 47.6% of women with pure cervical glandular neoplasia (adenocarcinoma or CGIN) compared with 12.8% with squamous cell lesions (CIN2/3 or SCC): P = 0.0001. Thus, colposcopy was more sensitive for detecting squamous cell abnormalities than their glandular counterparts. Although cervical adenocarcinomas are less amenable to prevention by screening than cervical SCC, in our study cervical cytology predominantly detected these abnormalities at their early asymptomatic stages. Conclusion: At least CIN2 was found in 81.5% in women referred with cervical cytology reporting ?glandular neoplasia. A thorough evaluation of the whole genital tract is needed if colposcopy is negative.     

Outcomes of cervical liquid-based cytology suggesting a glandular abnormality

Objective: To ascertain the positive predictive value of both ?glandular neoplasia (national standard code 6) and borderline change (national standard code 8) in glandular cells in liquid‐based cervical cytology specimens in Cardiff and Vale NHS Trust and to outline the histological outcomes of these cases. Method: Eighty‐nine liquid‐based (Surepath?) cervical cytology cases were retrospectively identified from a 2‐year period (January 2005 to December 2006) and correlated with histopathological diagnoses. Results: Initial punch biopsy histology revealed 18 cases (21%) of cervical glandular intraepithelial neoplasia (CGIN). A further nine cases (10%) of CGIN were identified following local excision or hysterectomy. Ten cases of invasive malignancy were identified: four endocervical adenocarcinomas (all node negative, TNM stage T1b1), five endometrial adenocarcinomas and one squamous cell carcinoma. There were 10 with high‐grade cervical intraepithelial neoplasia (CIN) alone. Women diagnosed with endometrial malignancy presented later with an average age of 64.6 years compared with 34.9 years for endocervical lesions. Taking high‐grade CIN or worse as a positive outcome, the overall positive predictive value (PPV) of glandular abnormalities on cytology (both code 6 and 8) was 58.1% [95% confidence interval (CI) 47.8, 68.4]. PPV for borderline change in glandular cells alone was 24.1% (95% CI 8.5, 39.6) and for ?glandular neoplasia alone 75.4% (95% CI 64.3, 86.5). Conclusion: With our interpretation of the classification, women with cytological diagnoses of glandular neoplasia of the cervix should initially be investigated by local resection rather than punch biopsy, and those with borderline change in glandular cells with repeat cytology.     

An audit of liquid‐based cervical cytology screening samples (ThinPrep and SurePath) reported as glandular neoplasia

S. A. Thiryayi, J. Marshall and D. N. Rana
An audit of liquid‐based cervical cytology screening samples (ThinPrep and SurePath) reported as glandular neoplasia Objectives: The aims of this study were to assess the number of cases diagnosed as glandular neoplasia (national report code 6) of cervical (6A) and non‐cervical (6B) types on ThinPrep (TP) and SurePath (SP) liquid‐based cytology (LBC) samples and to calculate the positive predictive value (PPV) of these diagnoses for significant glandular and/or squamous pathology for local audit and as a contribution to national data on glandular neoplasia. Methods: A computerized search identified all screening LBC samples reported as glandular neoplasia during the 24‐month period from January 2006 to December 2007. Corresponding histology samples were identified, with a minimum follow‐up period of 6 months for each case. Results: A total of 70 samples, representing 70 patients, were reported as glandular neoplasia, 39 TP (55.7%) and 31 SP (44.3%), with 46 samples (31 TP, 15 SP) reported as 6A and 24 samples (eight TP, 16 SP) as 6B. PPV of glandular neoplasia was calculated for a biopsy diagnosis of cervical glandular intraepithelial neoplasia/adenocarcinoma and/or cervical intraepithelial neoplasia (CIN) 2 or worse. The PPV of 6A was 100% for both TP and SP. The PPV of 6B for adenocarcinoma was 62.5% for TP and 66.7% for SP. The combined PPV for 6A + 6B was 92.3% for TP, 83.3% for SP and 88.4% combined. The overall pick‐up rates for the two methods were significantly different (TP 0.031%, SP 0.052%; P = 0.014). Histology showed only CIN3 with endocervical crypt involvement in nine TP cases and one SP case.     

Outcomes of pregnant patients with Pap smears classified as atypical glandular cells

J. Slama, P. Freitag, P. Dundr, J. Duskova, D. Fischerova, M. Zikan, I. Pinkavova and D. Cibula
Outcomes of pregnant patients with Pap smears classified as atypical glandular cells Objectives: The incidence of cervical cancers increases with age. Due to the trend of increasing age of first pregnancy, abnormal Pap smears including those classified as atypical glandular cells (AGC) are being found more often in early pregnancy. Once invasive cancer is excluded, conservative management of squamous intraepithelial lesions (SIL) in pregnancy is considered safe; however, optimal management of AGC is not well established. The aim of our study was to evaluate the outcome of patients with AGC diagnosed from smears during pregnancy. Methods: The study included 17 patients referred to us in early pregnancy with Pap smears reported as AGC: 11 not otherwise specified (AGC‐NOS), five favour neoplasia (AGC‐FN) and one adenocarcinoma in situ (AIS). Thirty‐one with high‐grade SIL (HSIL) Pap smears confirmed on punch biopsy in early pregnancy comprised a control group. Human papillomavirus (HPV) positivity was found in seven patients with persistent AGC‐NOS (including all four who had CIN3 postpartum). All the women were initially examined by expert colposcopy and those with AGC‐FN or AIS smears also by transrectal ultrasound to exclude invasive endocervical cancer. Follow‐up controls were carried out every 8–12 weeks and, if there were no signs of progression, revaluation was scheduled 6–8 weeks after delivery. Results: The mean age of the women was 31.4 years. Conization in one patient in the study group was performed in the 16th week of pregnancy due to colposcopic signs of microinvasive squamous cell cancer confirmed on histology. Progression to invasive cancer was not found in any of the other 16 patients in the study group or in the control group. Cervical intraepithelial neoplasia or AIS was confirmed postpartum by conization or punch biopsy in 47.1% (8/17) of patients in the study group and, in 77.4% (24/31) of patients in the control group. Conclusions: Conservative management of women with AGC in pregnancy is safe where invasive cancer is excluded. As histological verification of glandular pre‐cancerous lesions by punch biopsy is not reliable and the postpartum regression rate cannot be determined precisely, conization should be performed in all cases with AGC‐FN or AIS. Triage of persistent AGC‐NOS with HPV testing is useful in distinguishing significant underlying lesions.     

Clinical significance of atypical glandular cells by the 2001 Bethesda System in cytohistologic correlation

OBJECTIVE: To evaluate incidence, cytology findings and pathology outcome of atypical glandular cells (AGC) in Pap smears according to the 2001 Bethesda criteria. STUDY DESIGN: From 103,073 consecutive Pap smears, 113 (0.1%) AGC cases were identified. Of these, 91 (80%) had adequate histologic evaluation included in this study. RESULTS: Abnormal histology findings were seen in 38 patients (42%). Final pathology results revealed 14 endometrial adenocarcinomas, 5 endocervical adenocarcinomas, 1 cervical squamous cell carcinoma, 1 endometrial stromal sarcoma, 6 other malignancies, 4 endocervical adenocarcinomas in situ, 4 cases ofendometrial complex byperplasia, 1 case of endocervical glandular dysplasia and 2 cases of cervical intraepithelial neoplasia 3 with glandular involvement. Women with AGC, favor neoplasia, were more likely to have significant pathology than those with AGC, not otherwise specified, 74% vs. 33% (p = 0.002). Some characteristic background cytologic findings were also noticed in most cases of endometrial, fallopian tube and endocervical adenocarcinoma. CONCLUSION: A diagnosis of AGC is more clinically significant by the 2001 Bethesda System, especially the "AGC, favor neoplastic" category. Some background cytologic features are important because they are indicators of malignancy.     

Atypical glandular cells in cervical smears: histological correlation and a suggested plan of management based on age of the patient in a low-resource setting

Objectives:  To perform an audit of all smears reported as atypical glandular cells (AGC) using the Bethesda system (TBS) 2001.
Methods:  A total of 18 376 cervical smears were screened from January 2005 to June 2007, of which 65 cases were reported as AGC. Follow-up histology was available in 31 cases (47.7%), in whom a detailed cytological/histological correlation was carried out.
Results:  AGC constituted 0.35% of all Pap smears. Follow-up histology was normal or benign in 20 cases, whereas a squamous or glandular abnormality was seen in 11 cases. Squamous abnormalities included one case each of cervical intraepithelial neoplasia (CIN)1, CIN2 and CIN3 and five cases of squamous cell carcinoma. All glandular epithelial abnormalities were endometrial in origin and included two endometrial adenocarcinomas and one uterine serous carcinoma. Neither in situ nor invasive adenocarcinoma of the endocervix was observed. Review of smears and reclassification as AGC, not otherwise specified and favour neoplasia revealed a higher proportion of abnormality in the latter group, reaffirming the utility of subtyping. The median age of women with AGC was 41 years. The outcome was analysed with respect to the median age. In women aged equal or more than 40 years, AGC reflected a high-grade squamous or glandular epithelial abnormality in 50% of cases compared with none in those less than 40 years old ( P  = 0.010).
Conclusion:  The age of the woman as well as the subtype of atypical glandular cells influences outcome and hence must be taken into consideration while formulating an acceptable management strategy in these women in a low-resource setting.     

Cytology suggestive of glandular neoplasia: outcomes and suggested management

Eighty-three cases having a cervical smear result showing abnormal glandular cells were identified and matched up with the diagnostic histology result. Thirty-four (41.0%) were associated with malignancy and 26 (31.3%) with a cervical intraepithelial lesion without invasion. Thirty-eight (45.8%) had conditions of the cervix as follows: 12 cases had invasive disease of the cervix; nine (10.8%) adenocarcinoma of cervix and three (3.6%) squamous carcinoma of cervix. Nineteen (22.9%) had cervical intraepithelial neoplasia (CIN/SIL) alone and seven (8.4%) had cervical glandular intraepithelial neoplasia (CGIN) +/- CIN. There were 16 (19.3%) cases with malignancies of the uterine corpus and six (7.2%) had a malignancy arising from another primary site. Twenty-three (27.7%) had no malignant or pre-malignant condition. The risk of malignancy was related to age and ranged from 18.2% in those under 35 years to 67.9% in those 55 years and over. A protocol for the management of these cases is described.     

Increased diagnostic accuracy of atypical glandular cells in cervical liquid‐based cytology using cell blocks

E. K. J. Risse, J. P. Holierhoek, E. M. Meijer‐Marres, E. Ouwerkerk‐Noordam and M. E. Boon Increased diagnostic accuracy of atypical glandular cells in cervical liquid‐based cytology using cell blocks Objective: The purpose of this study was to reduce the number of diagnoses of atypical glandular cells (AGC). Residual material from the cervical ThinPrep® samples (Hologic, Marlboruogh, MA, USA) was used for cell blocks (CB) and immunohistochemistry (IHC). Methods: In 2007 there were 87 patients (0.12% of tests) with AGC on liquid‐based cytology (LBC) in the Leiden Cytology and Pathology Laboratory (LCPL) using the Bethesda System 2001 (TBS). CB with IHC was used for 26 of these cases. The vials still containing the brush (Cervex‐Brush^® Combi) were placed in a shaker for 10 minutes to dislodge the material trapped between the bristles. The residual sampling fluid was used to prepare paraffin sections (Shandon Cytoblock^®) stained with Papanicolaou and immunostaining. Results: Four of five cases with AGC not otherwise specified (NOS) were diagnosed with CB/IHC as benign mimics (endometrium, tubal metaplasia, follicular cervicitis, microglandular hyperplasia) and one of four with AGC‐favour neoplasia (FN) (endocervical polyp). In one of five cases with AGC‐NOS and in two of seven with AGC‐FN, CIN3 was found on subsequent histological biopsy. Of six cases diagnosed as adenocarcinoma in situ (AIS) on LBC with CB/IHC the diagnosis was confirmed in four; one was adenocarcinoma and one glandular atypia. Of eight cases diagnosed as adenocarcinoma on cytology and CB/IHC, the diagnosis was confirmed in three. The other five cases were found to be one each of AIS, squamous cell carcinoma, CIN3, CIN2 with glandular atypia, and cervical endometriosis. Conclusions: By reducing the number of benign mimics of AGC, we achieved a high proportion (16/26; 61.5%) of neoplastic or preneoplastic lesions (glandular or squamous) on histological outcome potentially avoiding colposcopy. Histological biopsy verification by the gynaecologist is needed for final diagnosis of AGC‐FN, AIS and adenocarcinoma.     

Diagnostic and therapeutic dilemma associated with atypical glandular cells on liquid‐based cervical cytology

K. Chummun, M. Fitzpatrick, P. Lenehan, P. Boylan, E. Mooney and G. Flannelly
Diagnostic and therapeutic dilemma associated with atypical glandular cells on liquid‐based cervical cytology Background: In 2008, the management of women in Ireland with atypical glandular cells changed to immediate referral to colposcopy. The optimal management of these women is unclear. A balance between the detection of occult disease and overtreatment is required. Methods: Our study aim was to document the experience of this policy at the National Maternity Hospital, Dublin. Information from the computerized data management system was analysed with the statistical package SPSS. Results: In 2009, 156 women attended colposcopy following a single atypical glandular cell diagnosis on liquid‐based cytology. The mean age was 41 years. Thirty (19.2%) women had abnormal vaginal bleeding, 31 (19.9%) were smokers and 34 (21.8%) had received previous treatment. The colposcopy was satisfactory in 125 (80.1%) and unsatisfactory in 31 (19.9%). Cervical histology was available for 146 (93.6%) women: 57 excisional procedures and 89 diagnostic biopsies. Abnormal histology was detected in 46 women (31.5%). Four women (2.7%) had invasive cancer, five (3.4%) had adenocarcinoma in situ, 21 (14.4%) had cervical intraepithelial neoplasia (CIN) grade 2 or 3 and 16 (11.0%) had CIN1. No abnormality was detected in 100 women (68.5%), including 35 (61.4%) of those who had undergone excisional procedures. The colposcopic impression in this group was unsatisfactory in 10 women (28.6%), glandular abnormalities in six (17.1%), high‐ and low‐grade changes in 12 (34.2%) and six (17.1%) women, respectively, and normal in one (2.9%). The findings were essentially negative in the remaining 10 women: overall, 30 (19.2%) of the 156 women referred to colposcopy had at least CIN2. Conclusion: This study confirmed significant levels of high‐grade disease in women referred to colposcopy with atypical glandular cells on cytology. Concerns about undetected endocervical disease resulted in high levels of negative excisional biopsies. Alternative strategies, including endometrial sampling, human papillomavirus testing and discussion at clinicopathological meeting, should be considered.     

Cervical intraepithelial neoplasia grade III (CIN III) and invasive cervical carcinoma: the yawning gap revisited and the treatment of risk

In a 3-year study of the population of Southampton and south-west Hampshire there were 10 times as many cases of CIN III compared with invasive squamous carcinoma (700 compared with 70). The peak incidence of CIN III per 1000 screened women years was in those aged 25-29 years, which was 20 years earlier than the peak incidence of invasive cervical cancer per 1000 women years at risk. Ninety percent of CIN III was diagnosed in women under 50 years. There were 14 cases of cervical glandular intraepithelial neoplasia grade III (CGIN III), three coexisting with CIN III, all in women aged under 50 years: the gap between intraepithelial and invasive lesions was not seen for glandular neoplasia. Although referral was for at least moderate dyskaryosis in 86.8% of women with CIN III or CGIN III, most had been screened previously, either having had mild abnormalities requiring repeat cytology (39.8%) or negative cytology (34.5%). Only 12 women aged > or = 50 years had previous negative cytology: 21.4% compared with 35.6% of women aged < 50 years (P = 0.034). The results of this study suggest that the best opportunity for preventing invasive squamous cell carcinoma lies in screening women aged 20-39 years when the incidence of CIN III in the screened population is highest and before the peak incidence of invasive disease. The results also indicate the importance of repeated screening and follow up of minor cytological abnormalities in the detection of CIN III. The benefit of screening must be regarded as a treatment of risk, since it is almost certain that a high proportion of CIN III regresses or persists unchanged.     

Clinical significance of atypical glandular cells of undetermined significance. A follow-up study from an academic medical center

OBJECTIVE: To determine the rate of atypical glandular cells of undetermined significance (AGUS) and the incidence of subsequent clinically significant lesions. STUDY DESIGN: A computer-based search of our cytology laboratory files was performed for cervicovaginal smears diagnosed as AGUS from January 1996 to December 1996. RESULTS: In 43,456 cervicovaginal smears examined during the 12-month period, AGUS was reported in 222 (0.5%) cases, with follow-up in 191 (86.0%) (133 [59.9%] biopsies and 58 [26.1%] repeat cervicovaginal smears). Among the patients with repeat cervicovaginal smears, 1 (1.7%) had a high grade squamous intraepithelial lesion, and 10 (17.2%) had persistent AGUS/atypical squamous cells of undetermined significance; the remainder were within normal limits. Thirty-three (24.8%) patients had preneoplastic or neoplastic, squamous or glandular lesions on biopsy (8 [6.0%] cervical intraepithelial neoplasia [CIN] 1, 18 [13.5%] CIN 2/3 and 7 [5.3%] endometrial adenocarcinomas). Half the patients with CIN 2/3 also had evidence of endocervical gland involvement. Squamous lesions were seen more commonly in premenopausal women, while glandular lesions were noted predominantly in postmenopausal women. Patients with a prior abnormal gynecologic history or a concomitant diagnosis of squamous intraepithelial lesion (SIL) had a higher incidence of significant lesions on subsequent biopsy. CONCLUSION: Our incidence of AGUS was 0.5%, similar to that in other published reports. AGUS is associated with a significant number of squamous or glandular, premalignant or malignant lesions. A majority of these lesions are high grade SIL, often with endocervical gland involvement. A small but significant number of patients had a glandular malignancy. Our results justify close and persistent follow-up for patients with a diagnosis of AGUS on cervicovaginal smears.     

How predictive is a cervical smear suggesting glandular neoplasia?

The prevalence of endocervical adenocarcinoma and its precursors has increased, in part due to increased diagnostic awareness of these lesions. To date, limited information has been published regarding the predictive value of glandular abnormalities in cervical smears. This study details the histological follow up of 418 cervical smears showing glandular abnormality, reported in our department over a six year period from 1993 to 1998. Histological follow up was available for 395 of the 418 smears (94.50%). The overall positive predictive value (PPV) for this group of smears was 72.66% for either significant glandular or squamous pathology (at least low grade cervical glandular intraepithelial neoplasia or CIN2 on follow up biopsy), and 55.70% for significant glandular pathology alone. Examination of subcategories of abnormal glandular smear showed that the PPV increased with the degree of abnormality reported within the smears.     

Decrease in numbers of glandular cell groups in post-LLETZ liquid-based cytology preparations

Objective:  Large loop excision of the transformation zone (LLETZ) has become standard of care in the management of cervical squamous neoplasia and with cone biopsy glandular intraepithelial neoplasia. Controversy remains about the long-term effects of this traumatic procedure. The aim of this study was to count and compare the number of endocervical glandular cell groups in pre- and post-LLETZ cervical preparations using liquid-based cytology to establish a cyto-morphological correlate of destruction of the transformation zone.
Methods:  The cytology/histology correlation audit records of the Cytopathology Department of St Luke's Hospital in 2003 and early 2004 were used to select patients with a cytological diagnosis of high grade dyskaryosis followed by LLETZ. Only those cases with post-LLETZ cytological follow-up were selected. Cases using conventional smears were excluded. One hundred and twenty slides (60 pairs of slides) in total were retrieved. The cases underwent review and all groups of >3 glandular cells in each slide were counted by AM while blinded as to whether smears were pre- or post-LLETZ. Medians were compared using a Mann–Whitney U -test.
Results:  The median number of groups of endocervical glandular cells of the pre-treatment group was 5.5 and of the post-treatment group was 2.0. There were significantly fewer endocervical glandular cell groups in the post-LLETZ population ( P  = 0.03).
Conclusions:  The number of endocervical glandular groups in cervical cytological preparations decreases significantly following LLETZ procedure. This suggests that cytological follow-up may not be as useful in glandular neoplasia cases. Few or absent glandular cell groups in post-LLETZ preparations may have implications for adequacy assessment.     

Atypical squamous cells and low‐grade squamous intraepithelial lesion in cervical cytology: cytohistological correlation and implication for management in a low‐resource setting

N. Gupta, R. Srinivasan, R. Nijhawan, A. Rajwanshi, P. Dey, V. Suri and L. Dhaliwal Atypical squamous cells and low‐grade squamous intraepithelial lesion in cervical cytology: cytohistological correlation and implication for management in a low‐resource setting Objectives: To perform an audit of all cervical smears reported as atypical squamous cells (ASC) and low‐grade squamous intraepithelial lesion (LSIL) as in the Bethesda system (TBS) 2001, and determine their histological follow‐up and outcome when available, in order to define the threshold for colposcopic referral. Material and methods: A total of 25 203 cervical smears were screened over a period of 3 years (January 2006 – December 2008) and all ASC and LSIL smears were reviewed with the corresponding histological follow‐up. All cervical intraepithelial neoplasia (CIN) grade 2 lesions and above (CIN2+) were considered as clinically significant lesions for analysis. Results: Out of 25 203 cervical smears, 424 (1.7%) were reported as ASC and 113 (0.4%) as LSIL. Additionally, three were reported as atypical cells, not otherwise specified. The ASC : SIL ratio was 2.18 : 1. Follow‐up histology was available in 153 (36.8%) of the ASC cases and revealed CIN2+ lesions in 22 (14.4%). Follow‐up histology was available in 50 (44.2%) of LSIL cases and revealed clinically significant abnormalities in five (10%), all of which were CIN2. CIN3 and invasive squamous carcinomas were seen in 5.9% and 1.4%, respectively, of cases of ASC, and not seen in LSIL. Reclassification of ASC smears into ASC‐US (ASC‐undetermined significance) and ASC‐H (ASC‐ high grade SIL not excluded) revealed ASC‐H in 2.6% of all ASC smears, with a clinically significant outcome in 45.4%. Conclusion: In a low‐resource setting where human papillomavirus testing is unaffordable, the threshold for colposcopic referral and follow‐up histology should be ASC rather than SIL.     

Borderline nuclear change,high‐grade dyskaryosis not excluded: current concepts and impact on clinical practice

S. S. Hoo, A. Patel, H. Buist, K. Galaal, J. D. Hemming and R. Naik Borderline nuclear change, high‐grade dyskaryosis not excluded: current concepts and impact on clinical practice Objective: Borderline nuclear change, high‐grade dyskaryosis not excluded (B/HG) is a subcategory of the borderline category recommended by the British Society for Clinical Cytology as warranting direct referral to colposcopy. This subcategory is equivalent to the Bethesda category of atypical squamous cells, cannot exclude high‐grade squamous intraepithelial lesion (ASC‐H). The purpose of this study was to determine the validity and accuracy of using B/HG to identify potential cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+). Methods: Data were collected from the hospital pathology database for borderline, B/HG and high‐grade cytology (moderate dyskaryosis and above), and their respective histological and colposcopic outcomes. SPSS was used for data analysis. Results: Of the 84 799 total cytology samples screened between July 2006 and December 2009, 5225 (6.1%) were reported as borderline, 309 (0.4%) as B/HG and 1222 (1.4%) as high‐grade cytology. Thus, B/HG comprised 5.9% of the overall borderline category, in keeping with national guidelines (<10%). CIN2+ was confirmed in 86.6% of high‐grade, 40.8% of B/HG and 3.0% of borderline cytology. Of 309 women reported with B/HG cytology, 239 had colposcopy. Colposcopic appearances showed a positive predictive value (PPV) of 71.8% for detecting CIN2+ and a negative predictive value of 60.7%. Conclusions: The B/HG category was associated with a significantly higher incidence of CIN2+ compared with borderline cytology as a whole. This refining performance justifies its existence. Colposcopic appearances had a high PPV for detecting CIN2+. Therefore, colposcopy is recommended in patients with B/HG cytology and treatment should be offered if high‐grade colposcopic changes are seen.     

Cervical squamous intraepithelial lesions and associated cervical infections in an HIV‐positive population in Rural Mpumalanga,South Africa

P. J. Swanepoel, P. Michelow, R. Du Plessis, I. G. Proudfoot, G. A. Tarr, S. L. Bockel, C. J. Swanepoel
Cervical squamous intraepithelial lesions and associated cervical infections in an HIV‐positive population in Rural Mpumalanga, South Africa Background: The incidences of genital human papillomavirus (HPV) infection, associated squamous intraepithelial lesions and cervical squamous cell carcinoma are significantly increased in HIV‐positive women. The role of other cervicovaginal infections in the acquisition of the HPV infection, cervical carcinogenesis and genital HIV infection remains largely speculative. Methods: A retrospective study was conducted including 1087 HIV‐positive women in rural Mpumalanga province, South Africa, for the period 1 May 2009 to 31 August 2010. For each patient, the age at first presentation, cervical cytological diagnosis, subsequent follow‐up cytology and histology, and microscopically visible infections (including endemic Bilharzia) were tabulated and statistically analysed. Results: The prevalence of low‐grade squamous intraepithelial lesion (LSIL), high‐grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma, atypical squamous cells of undetermined significance (ASC‐US) and atypical squamous cells, cannot exclude HSIL (ASC‐H) in the study population were 22.1%, 30.9%, 0.6%, 13.5% and 4.0%, respectively. LSIL, HSIL and squamous cell carcinoma were diagnosed, respectively, at the average ages of 35.7, 37.9 and 37.2 years. Four patients with cervical intraepithelial neoplasia grade 1 (CIN1), 32 with CIN2/CIN3 and two with cervical squamous cell carcinoma were also diagnosed with Bilharzia. Of the other infections only bacterial vaginosis had a positive statistical correlation with HPV‐induced cervical abnormalities (LSIL, HSIL or squamous cell carcinoma). Conclusion: This study confirms the high prevalence of progressive HPV‐associated cervical disease in a rural Southern African HIV‐positive population, which is at least equal to or worse than in other African HIV‐positive studies. The high incidence of Bilharzia infection in those cases that underwent cervical cone excision suggests a possible relationship with progressive HPV disease and cervical carcinogenesis. Bacterial vaginosis (perhaps in combination with Bilharzia) may compromise the normal barriers against HPV and HIV infection.     

Endocervical glandular cell abnormalities in conventional cervical smears: evaluation of the performance of cytomorphological criteria and HPV testing in predicting neoplasia

Objective:  To analyse the correlation between cytomorphological criteria in smears with atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) and human papillomavirus (HPV) reflex test results with different neoplastic histological diagnoses, particularly to distinguish between glandular and squamous neoplasia.
Methods:  A series of 155 women with glandular abnormalities in their conventional cervical smears was included: 106 with AGC, 35 with AGC associated with high-grade squamous intraepithelial lesion (HSIL) and 14 with AIS. Two reviewers evaluated 35 cytomorphological criteria and hybrid capture II (HCII) was performed in all cases. Colposcopy was carried out in all cases and biopsy in 126/155. For statistical purposes, predictive values and odds ratio (OR) were calculated, followed by chi-square automatic interaction detection.
Results:  Histology detected 56 cases of squamous and 17 of glandular intraepithelial or invasive neoplasia. Predictive values of the papillary groups and feathering criteria for glandular neoplasia were, respectively, 80.0% and 73.3%. Feathering was the criterion with the highest OR for distinguishing glandular from squamous neoplasia and also for distinguishing between glandular and non-neoplastic diagnosis. Rosettes and pseudostratified strips did not perform as well. Multivariant Classification and Regression Trees analysis identified feathering as the best criterion for distinguishing between glandular, squamous and non-neoplastic diagnoses regardless of HPV status.
Conclusions:  Feathering was the best criterion for predicting glandular neoplasia.     

European guidelines for quality assurance in cervical cancer screening: recommendations for clinical management of abnormal cervical cytology, part 1

The current paper presents the first part of Chapter 6 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. It provides guidance on how to manage women with abnormal cervical cytology. Throughout this article the Bethesda system is used for cervical cytology terminology, as the European guidelines have recommended that all systems should at least be translated into that terminology while cervical intraepithelial neoplasia (CIN) is used for histological biopsies (Cytopathology 2007; 18 :213–9). A woman with a high‐grade cytological lesion, a repeated low‐grade lesion or with an equivocal cytology result and a positive human papillomavirus (HPV) test should be referred for colposcopy. The role of the colposcopist is to identify the source of the abnormal cells and to make an informed decision as to whether or not any treatment is required. If a patient requires treatment the colposcopist will decide which is the most appropriate method of treatment for each individual woman. The colposcopist should also organize appropriate follow‐up for each woman seen. Reflex testing for high‐risk HPV types of women with atypical squamous cells (ASC) of undetermined significance with referral for colposcopy of women who test positive is a first option. Repeat cytology is a second possibility. Direct referral to a gynaecologist should be restricted to special circumstances. Follow‐up of low‐grade squamous intraepithelial lesion is more difficult because currently there is no evidence to support any method of management as being optimal; repeat cytology and colposcopy are options, but HPV testing is not sufficiently selective, unless for older women. Women with high‐grade squamous intraepithelial lesion (HSIL) or atypical squamous cells, cannot exclude HSIL (ASC‐H) should be referred without triage. Women with glandular lesions require particular attention. In a subsequent issue of Cytopathology, the second part of Chapter 6 will be presented, with recommendations for management and treatment of histologically confirmed intraepithelial neoplasia and guidance for follow‐up of special cases such as women who are pregnant, postmenopausal or immunocompromised.     

Is a liquid‐based cytology more sensitive than a conventional Pap smear?

K. Sigurdsson
Is a liquid‐based cytology more sensitive than a conventional Pap smear? Background: The comparative sensitivity of liquid‐based cytology (LBC) test and conventional Papanicolaou (Pap) smears is controversial. Material and methods: This study analyses the distribution of cytology, histology, colposcopy and large loop excision of the transformation zone among women screened in Iceland with LBC at the Cancer Detection Clinic in Reykjavik and with a conventional Pap smear outside the Detection Clinic in 2007–2011. The study material included 42 654 LBC tests from 20 439 women and 103 909 Pap smears from 61 574 women. The period 2000–2004 is used to correct for potential bias as a result of unequal distribution of the studied parameters between the study sites before the introduction of LBC. Results: The observed results indicated that women screened with an LBC sample had significantly decreased detection rates of inadequate smears, increased detection of low‐grade squamous intraepithelial lesion (LSIL)/atypical cytology and referrals to colposcopy, and an increased detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) irrespective of age. LBC increased significantly the detection rates of high‐grade squamous intraepithelial lesion or worse (HSIL+) cytology and CIN3+ histology only in women under 40 years of age. Taking into consideration the unequal prevalence of the studied parameters between the study sites in 2000–2004 indicated, however, that LBC only affected the rate of inadequate and low‐grade cytology tests under the age of 40 years. Positive predictive values for CIN2+ were not significantly different between the tests. Conclusions: The study results support the view that LBC is no more sensitive than Pap smears for the detection of HSIL+ and CIN2+ irrespective of age. LBC decreased the rate of inadequate smears, but increased the rate of low‐grade cytology under the age of 40 years and decreased the total rate of abnormal smears over the age of 40 years.