Evaluation of colposcopy in the postmenopausal woman

Cytology, colposcopy and histology findings in 121 postmenopausal and 120 premenopausal women referred to the Oxford colposcopy clinic were compared; 88% of postmenopausal and 69% of premenopausal women were referred by their general practitioners. Cervical smear reports, within the preceding 5 years, were available for 21% of the postmenopausal and 54% of the premenopausal women. Colposcopic assessment was technically unsatisfactory in 53% of the postmenopausal women because the transformation zone was not completely visible, this contributed to a cone biopsy rate of 71% in this group. Only 17% of postmenopausal women with cervical intraepithelial neoplasia (CIN) were managed with local ablative techniques compared with their use in 61% premenopausal patients overall and in over 70% of the women under 35 years. Local ablation was used in 10 of 14 women using hormone replacement therapy. The cytological false negative rate for postmenopausal Papanicolaou class III, IV and V smears was 9% but for persistent class II inflammatory smears it was 43%. Nine of 23 postmenopausal women with persistent inflammatory dyskariosis despite antibiotic or antifungal treatment were found to have colposcopic appearances of CIN and four had microinvasion or invasion. Colposcopy revealed probable microinvasive or invasive disease in 17 postmenopausal women, seven of whom had class II or III cytology.     

Contribution of human papillomavirus testing by hybrid capture in the triage of women with repeated abnormal pap smears before colposcopy referral

OBJECTIVE: The purpose of this work was to evaluate the ability of testing for high-risk human papillomavirus (HPV) types using the hybrid capture technique to predict the presence of cervical intraepithelial neoplasia (CIN) II,III in patients with repeated atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LGSIL) on Pap smears. METHODS: Hybrid capture testing and tissue biopsy were performed on 503 consecutive women with ASCUS or LGSIL on repeated Pap smears who were referred for colposcopy. RESULTS: A highly significant association (P < 0.0001) was found between a positive test for high-risk HPV types and CIN II,III, with an 87.0% positive predictive value and a 95.7% negative predictive value. In 226 women with ASCUS on repeated Pap smears, a positive test for high-risk HPV types had a 85.7% sensitivity and a 97% specificity for CIN II,III. In 277 patients with LGSIL on repeated Pap smears, a positive test for high-risk HPV types had an 88.2% sensitivity and a 94.7% specificity for CIN I,II. Reserving colposcopy examination for women who were positive for high-risk HPV types would have reduced the number of referrals for colposcopy to 24.6% and maintained a sensitivity of 87.0% for CIN II,III. CONCLUSIONS: A positive hybrid capture test for high-risk HPV types was highly sensitive and specific for the presence of CIN II,III in patients with ASCUS and LGSIL on repeated Pap smears. We believe that improved methodology will eventually enable more selective colposcopy referrals without affecting patient safety among these women.     

Human papillomavirus in women. A three-year experience in a county hospital colposcopy clinic.

The human papillomavirus (HPV) has been associated with cervical dysplasia and carcinoma. This report summarizes the authors' experience with HPV-related problems over three years, 1987-89, while managing 1,644 women at a county hospital colposcopy clinic. Probes for HPV DNA were not used, and the diagnoses were made with cytologic and histologic criteria alone. The percentage of patients referred to the clinic with HPV found on routine Papanicolaou smears rose significantly, from 3 in 1987 to 18 in 1989. Fifteen percent of those referred because of HPV on a Papanicolaou smear were found to have cervical intraepithelial neoplasia (CIN) grade II or III after they were evaluated at the clinic. Of the 367 cases of biopsy-proven cervical HPV, only 33 (9%) were recorded on Papanicolaou smears performed immediately before the biopsy, and 140 (38%) also had concomitant, biopsy-proven CIN, grade II or III. Of the 195 instances in which the colposcopic impression was simple HPV without CIN, 46 (24%) had high-grade CIN on biopsy. We conclude that the proportion of patients with HPV-associated problems is increasing, that the Papanicolaou smear is not sensitive in detecting cervical HPV infections, that patients with HPV changes found on Papanicolaou smears should be evaluated with colposcopy and that lesions that appear colposcopically to be simple HPV should undergo biopsy to rule out the presence of high-grade CIN.     

Cervicography to triage women with borderline or mild dyskaryotic cervical PAP smears

OBJECTIVE: To evaluate six years experience using cervicography to triage women with borderline or mildly dyskaryotic PAP smears to either immediate colposcopy or cytological surveillance. METHOD: Retrospective study of 1,436 women referred to the cervicography clinic of the Whittington Hospital, London. Women with suspicious cervigrams were examined colposcopically and biopsied. Women with normal appearances at cervicography were followed-up with cytology over a period of a least two years. RESULTS: Cervicography detected 281 out of 307 women with CIN 2/3 and 215 out of 264 women with CIN 1. The sensitivity of cervicography to detect CIN 1, 2 or 3 in women with minor PAP smear abnormalities was 92%. The specificity was 39% and 847 (59%) of the women were referred for colposcopy; 215 (15%) were lost to follow-up. CONCLUSIONS: Cervicography was a sensitive method to detect CIN in women with mild or borderline dyskaryosis on their PAP smears. However, the low specificity meant that a high proportion of the women were referred for colposcopy, and a significant proportion of women were lost to follow-up. Thus cervicography is not an efficient strategy for managing women with minor PAP smears abnormalities.     

Inflammatory atypia on cervical smears. A diagnostic dilemma for the gynecologist

In light of the current controversy on the significance, follow-up and management of women with cervical smears showing "inflammatory atypia" (IA), a study was conducted to correlate the initial cytologic diagnosis of IA with the follow-up findings in colposcopically directed cervical biopsies and smears. From March 1988 through June 1989, 70 women had two consecutive smears reported as IA; all underwent colposcopy and cervical biopsy. In 58 patients (83%) the biopsies and smears obtained during colposcopy were negative for condyloma and/or cervical intraepithelial neoplasia (CIN). Ten patients (14%) had condylomas, and two (3%) had condylomas with CIN (one CIN I and one II). The initial IA smears from those 12 patients were reviewed retrospectively: 2 showed condylomas (they had been undercalled), 5 were "suggestive of condyloma" (the atypical cells were too few or poorly preserved for a definitive diagnosis), and 5 showed IA. None showed cytologic evidence of CIN, most probably because of sampling error. Our results suggest that colposcopy is warranted after two consecutive diagnoses of IA on cervical smears, considering that 17% of the patients in our study showed underlying intraepithelial lesions of the cervix.     

Aggressive evaluation for atypical squamous cells in Papanicolaou smears

A retrospective study was done on women who had atypical Papanicolaou smears and were referred for immediate colposcopy. The smears were obtained during January 1985 to March 1989 at Edwards Air Force Base, California. Excluded from the evaluation were abnormal Papanicolaou smears with hyperkeratosis, parakeratosis and koilocytotic atypia suggestive of human papillomavirus (HPV) infection. The evaluation included colposcopy, colposcopically directed biopsies, endocervical curettage and repeat Papanicolaou smears. A total of 101 patients were included in the study. Cervical intraepithelial neoplasia (CIN) was seen in 29.7% (30 patients): 12.9% (13) CIN I, 12.9% (13) CIN II and 3.9% (4) CIN III. Carcinoma was seen in 3.9% (4) of the patients: 2.9% (3) was carcinoma in situ, and 0.99% (1) was invasive squamous cell carcinoma, stage IIb. HPV and dysplastic lesions were seen together in 19.8% (20) of the patients. HPV was seen alone in 45% (46). Twenty-one patients (20.8%) had no apparent lesions on colposcopy, although one developed microinvasive keratinizing squamous cell carcinoma within 36 months of colposcopy. Many significant lesions can go undetected for extended periods of time in women with atypical Papanicolaou smears, resulting in delayed management. Referral for immediate colposcopy is advocated strongly.     

Conservative management of the abnormal smear during pregnancy. A long-term follow-up

One hundred and thirty-two pregnant women who had a smear suggestive of cervical intra-epithelial neoplasia (CIN) II or more during the 10th to 12th gestational week, were followed with repeated smears and colposcopy every month and, when indicated, a colposcopically guided biopsy. Post-partum follow-up included cytology, colposcopy, portio biopsies and endocervical curettage. Seventy-nine women with normal findings post partum were checked once a year in a long-term study. A close correlation (71% of CINIII) was found between cytological and histological diagnoses in cases of persistent (three or more) abnormal smears. However, in women with regression of the cytological diagnosis, high frequencies of histologically verified CIN were found. Thus, 37.5% (18/48) of normal or CINI smears were histologically still CINIII. Histologically verified CIN during pregnancy, on the other hand, showed a post partum progression of two degrees or more of CIN in only two cases. Cytology seemed to be inappropriate post partum, with 23.3% smears which were normal or suggestive of CINI, when histology showed CINIII. In a long-term follow-up, 24% of women with a normal post partum follow-up for at least one year had a subsequent recurrence of CIN. It is concluded that follow-up of abnormal smears during pregnancy with repeated smears is not a reliable method. Post-partum follow-up should include at least colposcopy and a biopsy when indicated by the colposcopical examination. Women with a normal post partum follow-up constitute a high risk group for future recurrence of CIN and should be carefully followed for at least 5 years.     

Triage of atypical squamous cells of undetermined significance with hybrid capture II: colposcopy and histologic human papillomavirus correlation

OBJECTIVE: To estimate the effectiveness of Hybrid Capture II to predict high-grade cervical intraepithelial neoplasia (CIN) from a cytological cervical sample. Evidence of high-risk human papillomavirus (HPV) was also determined from biopsy samples using the polymerase chain reaction (PCR) for women referred with atypical squamous cells of undetermined significance (ASCUS) Papanicolaou smears. METHODS: We screened 8170 women with Papanicolaou smears, of whom 278 (3.4%) returned ASCUS. All ASCUS cases underwent colposcopy and Hybrid Capture II testing. High-grade CIN biopsy specimens were tested for high-risk HPV by PCR. RESULTS: Nearly 30% of ASCUS cases had CIN biopsy results (11.9% showing CIN II or CIN III and 17.6% showing CIN I). Hybrid Capture II positive rates were 93.3% for cases with CIN III, 72.2% for CIN II, and 51.0% for CIN I (P <.001). ASCUS-Premalignant Process Favored cases showed a 28.1% high-grade biopsy rate and a 100% Hybrid Capture II positive rate. For ASCUS-Undefined and ASCUS-Reactive Process Favored cases, Hybrid Capture II returned positive in 90.9% of CIN III and 61.5% of CIN II cases (P <.001). Sixty-nine of 178 (38.8%) patients with no evidence of CIN tested positive for Hybrid Capture II. Human papillomavirus deoxyribonucleic acid (DNA) high-risk subtypes were detected by PCR in the tissue of all high-grade CIN cases with negative Hybrid Capture II results. CONCLUSION: Hybrid Capture II returned negative in 25% of cases with biopsy-proven high-grade CIN with associated high-risk HPV DNA by PCR (non-Premalignant ASCUS subset), and positive in 39.3% of cases with normal results; this limits its clinical utility.     

Quality of follow-up of women with high grade squamous intra-epithelial lesion (HGSIL) cervical smears: results from a population-based organised screening programme

OBJECTIVE: After a HGSIL cervical smear, to appraise the diagnostic and treatment modalities by comparing with national recommendations. STUDY DESIGN: A clinical audit concerning 444 women with a HGSIL cervical smear, within the first 3 years of the programme. RESULTS: Among the 413 women followed-up (98%), the colposcopy rate reached 71% at 3 months and 81% at 1 year. It was lower for women who had a history of other abnormal Pap smears than for those with no gynaecological symptoms or past history (66% versus 87%, P = 0.02), it was higher when the cytology report showed a CIN III than when a CIN II was reported (84% versus 78%, P = 9 x 10(-4). After the colposcopy, 23 women (7%) were lost to follow-up. Among the 76 women without a colposcopy, 17 (22%) did not have any histological examinations during their follow-up. CONCLUSION: Measures to improve women's follow-up compliance and ensure appropriate physician behaviours are necessary to achieve better quality in this screening programme.     

Human papillomavirus testing improves the accuracy of colposcopy in detection of cervical intraepithelial neoplasia

To assess the performance of human papillomavirus (HPV) testing and colposcopy in detection of cervical pathology. A series of 389 women referred for colposcopy due to an abnormal Pap smear had cervical swabs analyzed for oncogenic (high-risk [HR]) HPV types using Hybrid Capture II (HC2) assay. Loop electrical excision procedure cone biopsy (88%) or colposcopic biopsy (11%) was used as the gold standard. Of the atypical squamous cells of undetermined significance (ASCUS) smears, 48% were positive for HR HPV, as compared to 76.3% of low-grade squamous intraepithelial lesions (LSIL) smears. HR HPV was detected in 66.7% and 90% of patients with cervical intraepithelial neoplasia (CIN) 1 and CIN2 (or higher), respectively. The sensitivity of the Pap smear using an ASCUS threshold in detecting high-grade CIN was 94.5% (95% confidence intervals (CI): 91-97%) and that of colposcopy 98.5% (95% CI: 95-99%). The respective specificities were 30% (95% CI: 17-28%) and 35.6% (CI: 29-42%). HC2 test had comparable sensitivity, 90% (95% CI: 85-93%), but higher specificity, 54.3% (95% CI: 47-61%). Combining HC2 test with Pap increased specificity, 66.7% and 41.3% for ASCUS and LSIL cutoff, respectively. The minor-abnormality threshold together with HC2 increased specificity of colposcopy with no changes in sensitivity. High viral load (>100 relative light unit/positive control) was associated with significant disease. HPV DNA testing improves the accuracy of colposcopy in the detection of high-grade CIN in women with ASCUS or LSIL smears.     

The accuracy of repeat cytology in women with mildly dyskaryotic smears

A special colposcopy clinic was established at the Royal Free Hospital to investigate women whose referral smears showed mild dyskaryosis. Of 200 women in the study, 66 (33%) had histologically proven CIN II or CIN III, 59 (29%) had CIN I or human papillomavirus changes, and 54 (27%) were considered normal. These findings demonstrate the importance of adequate diagnosis of this group of women. Of 143 women who had had a single mildly dyskaryotic smear, 45 (31%) had either CIN II or III. Age was not useful for predicting which women were at high risk of significant disease. Careful repeat cervical cytology correlated closely with the histological grade of the lesion. Repeat cytology was associated with an overall 24% false-negative rate, but most missed lesions were of low grade. Repeat cytology correctly identified 82% of all CIN lesions, and 93% of the most significant lesions (CIN II and III). Women who have a mildly dyskaryotic smear followed by a negative smear should not be considered normal, but careful repeat cytology can be considered a reasonably safe practice.     

The accuracy of repeat cytology in women with mildly dyskaryotic smears

Summary. A special colposcopy clinic was established at the Royal Free Hospital to investigate women whose referral smears showed mild dyskaryosis. Of 200 women in the study, 66 (33%) had histologically proven CIN II or CIN III, 59 (29%) had CIN I or human papillomavirus changes, and 54 (27%) were considered normal. These findings demonstrate the importance of adequate diagnosis of this group of women. Of 143 women who had had a single mildly dyskaryotic smear, 45 (31%) had either CIN II or III. Age was not useful for predicting which women were at high risk of significant disease. Careful repeat cervical cytology correlated closely with the histological grade of the lesion. Repeat cytology was associated with an overall 24% false-negative rate, but most missed lesions were of low grade. Repeat cytology correctly identified 82% of all CIN lesions, and 93% of the most significant lesions (CIN II and III). Women who have a mildly dyskaryotic smear followed by a negative smear should not be considered normal, but careful repeat cytology can be considered a reasonably safe practice.     

Underlying pathology of women with "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" smears, in a region with a high incidence of cervical cancer

AIM: To evaluate the histopathology of women who had "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions" (ASC-H) on cervical cytology in a region with high incidence of cervical cancer. METHODS: This study was conducted at Chiang Mai University Hospital, Chiang Mai, Thailand. All women with ASC-H, who had undergone colposcopic and histolopathologic evaluation between October 2004 and January 2007, were recruited. Similar cohorts with other squamous cell abnormalities on a Pap-smear, who had undergone colposcopy during the same period, were included as comparative groups. RESULTS: During the study period, 85 women who had ASC-H smears underwent colposcopic and histopathologic evaluation. The mean age was 45.3 years (range, 20-64 years). The histopathologic results of these 85 women were as follows: cervical intraepithelial neoplasia (CIN) II-III, 52 (61.2%); invasive cancer, 7 (8.2%); CIN I, 6 (7.1%); and no lesions, 20 (23.5%). The incidence of underlying CIN II or higher in an ASC-H smear (69.4%) was intermediate between atypical squamous cell of undetermined significance (22.7%), low-grade squamous intraepithelial lesion (44.7%) and high-grade squamous intraepithelial lesion (90.5%) smears. There was no statistically significant difference in the incidence of CIN II or higher between women who were 40 years old or more and those who were younger (68.7% and 71.4%, respectively, P=0.81), or between pre-menopausal and post-menopausal women (71.4% and 63.6%, respectively, P=0.49). CONCLUSION: Reporting ASC-H cytology in our population is strongly associated with significant cervical pathology, particularly invasive cancer that is possibly at a rate higher than previously reported. Women who have ASC-H smears should therefore be referred for immediate colposcopy regardless of age and menopausal status.     

20-year experience of follow-up of the abnormal smear with colposcopy and histology and treatment by conization or cryosurgery

During the period 1967 to 1977, 1466 women with Pap smears suggesting cervical epithelial neoplasia (CIN) II or worse were evaluated by colposcopy, portio biopsy, and endocervical curettage. Women who had CIN III were treated first by conization and later by cryosurgery. Cytological diagnosis was inaccurate compared to colposcopical and histological diagnosis, with 27% having a worse histological diagnosis. In 22% of the cases histology was two degrees less or worse than suggested by cytology. Presence of atypical vessels was associated with invasive cancer in 17% of cases. A total of 635 patients were treated by conization. After an average follow-up of 10 years, the cure rate was 96% compared to 87% by cryosurgery (104 cases). Hysterectomy was, mainly because of old age, performed on 154 patients; the cure rate was 97%. Although most treatment failures occurred within the first 5 years, some were seen after as long as 15-20 years.     

Frequency of cervical intraepithelial neoplasia grade II or worse in women with a persistent low-grade squamous intraepithelial lesion seen by Papanicolaou smears

Purpose

We investigated the frequency of cervical intraepithelial neoplasia (CIN) grade II or worse in low-income Brazilian women with persistent low-grade squamous intraepithelial lesions (LSIL).

Methods

A retrospective review of medical records was performed for all patients who underwent a loop electrosurgical excision procedure (LEEP) with "see and treat" strategy for persistent LSIL seen on Papanicolaou (Pap) smears (persisting >12 months in at least two consecutive tests, over a 50-month period. We assessed the colposcopy and histopathology results at the time of the procedure and at follow-up, using Pap and histopathology.

Results

Of 106 women, 48 (45.3 %) had no dysplasia by histopathology, 18 (17.0 %) had CIN I, 29 (27.4 %) had CIN II and 10 (9.4 %) had CIN III. Among the patients with CIN, 38 (66.7 %) performed the follow-up. Of these, only 4 (10.5 %) were classified as follow-up (+), all had CIN I. Women with initial CIN I had 16.7 % (n = 2) recurrences; those with initial CIN II had 5.9 % (n = 1); and those with initial CIN III had 11.1 % (n = 1) (p > 0.05).

Conclusions

A very high proportion of the women with persistent LSIL had CIN II/III on post-LEEP histopathology. Recurrence rates were equal to than those that originally caused the patients to be subjected to LEEP (LSIL). The benefits of the "see and treat" protocol by LEEP for persistent LSIL outweigh the risk of overtreatment, principally in low-resource settings where poor patient compliance is expected, as in Brazil.     

A retrospective study of cervical screening in women under 25 years (2005–2009)

Objective

Since 2003, when the age threshold of cervical screening in England has been raised from 20 to 25, there have been many calls to restore the previous starting age for cervical screening as there are concerns about the delaying of initiating cervical screening may result in an increase in the risk of cervical cancer. We conducted a retrospective study to analyse the safety of changing the starting age of cervical screening programme in England to the age of 25, by reviewing the cervical cytology performed in 426 women under 25 years in Bromley Borough of London, UK, between 2005 and 2009.

Study design

We conducted a retrospective analysis of 426 women under 25 years, who were referred with cervical smears taken at Bromley PCT’s to the colposcopy clinic at Bromley Hospitals, South London Healthcare NHS Trust, over a 4-year period, between 2005 and 2009. The colposcopy findings and histology results were reviewed and analysed.

Results

In our review, 44.80 % of smears showed mild dyskaryosis. 23 and 12 % showed moderate dyskaryosis and severe dyskaryosis, respectively. 11.2 % had borderline smear, and 0.2 % revealed glandular changes. On colposcopic examination, only 16.2 % (69) were reported as normal; however, 25.8, 20 % of the women were diagnosed with low and high grade abnormalities, respectively. 12 % (53) of the cases showed HPV-related changes, whereas no suspected malignancy was found. Colposcopic-directed cervical biopsy was obtained in 228 women (~54 %) depending on the colposcopic examination findings. The most histological finding was CIN I which constitutes 48 % (110) of all biopsies. However, 25 % (58) and 9 % (20) revealed CIN II and CIN III, respectively. The glandular changes noticed in only one case (0.44 %). The treatment was planned for 130 women, a significant proportion (30.5 %) of the 426 women who referred for colposcopy. The histological examination of the biopsies showed CIN in 91 % of the cases (115), 74.8 % (86) of them had CIN II (36) or CIN III (50). In addition, the glandular changes found in two cases (1.6 %). More importantly, there was one case diagnosed with micro-invasive cervical cancer (0.79 %) and this comprises 0.23 % of our sample.

Conclusion

In view of the size and the heterogeneity of our sample, it is difficult to recommend changing the starting age of the cervical screening programme. However, we strongly recommend to have a low threshold to offering cervical cytology to the women under 25 on clinical basis, particularly, after the recent introduction of HPV triage (outside the scope of this study), which will enable us to avoid the two main disadvantages of the early screening, namely over-diagnosis and over-treatment.     

Cervical intra-epithelial neoplasia and koilocytotic lesions of the lower genitalia in an Icelandic population

Abstract. This study is based on women who participated in cervical cancer screening and on 390 women referred from the screened group for colposcopy. The study analyzed the frequency of atypia, CIN and koilocytosis and evaluated the efficiency of cytologic vs. histologic diagnosis. The clinical expression of the koilocytotic lesions and the rate of infected partners were evaluated. In the screened population the prevalence of smears with atypia and CIN was 3.2% and that of koilocytosis 0.5%. In the colposcopic group the frequency of koilocytosis in the histologic sections was 98% compared to 18% of the smears. The koilocytotic lesions were mostly multicentric, subclinical and asymptomatic and often associated with normal cytology. The rate of infected partners of women with normal smears and non-symptomatic vulvar lesions was low (15%), increased if smears were abnormal (30%), and was highest when the partner had gross condylomata (89%). As to atypia and CIN, the rate of undegraded smears was 18%, false-negative smears 8%, undergraded colposcopic biopsies 33%, false-negative colposcopic biopsies 3%, and the false-negative rate of combined cytology and colposcopy was less that 1%. Colposcopy is recommended for unclassified CIN and CIN 2–3 repeat smear for atypia and CIN 1 and combined cytology and colposcopy for condylomata.     

Should women with postcoital bleeding be referred for colposcopy?

This study was to determine the risk of finding significant cervical pathological abnormality in women referred to the colposcopy clinic primarily because of postcoital bleeding. We evaluated the cervical smear history of such women and correlated this with any colposcopic or pathological abnormality. There were 142 women seen over a period of 12 months. The age range of the study population was 16 - 61 years (mean age of 34.1 years). There was no case of lower genital tract invasive neoplasia. Out of the 142 cases, 56 women (39.4%) had normal findings at colposcopy and 44 (31%) were secondary to cervical ectopy. A total of 27 (19%) had cervical intraepithelial neoplasia (CIN) out of which there were 15 (10.6%) cases of high-grade disease (CIN II and CIN III); and, 20 (74%) out of the 27 women with CIN had a recently negative cervical smear (within the previous 36 months). Seven women (4.9%) had benign cervical polyps that were removed during colposcopy. The frequency of finding invasive lower genital tract neoplasia in women with postcoital bleeding is low. However, a good proportion of them would have a diagnosis of cervical intraepithelial neoplasia even with a recently negative cervical smear. Therefore, postcoital bleeding should remain an indication for referral to the colposcopy clinic for a detailed evaluation of the lower genital tract.     

The cytological detection of persistent cervical intraepithelial neoplasia after local ablative treatment: a comparison of sampling devices.

OBJECTIVE: To determine whether the cytological detection of persistent cervical intraepithelial neoplasia (CIN) after local ablative treatment is improved by the use of sampling devices other than the Ayre's spatula. DESIGN: A randomized controlled study. SETTING: Lothian Area Colposcopy Clinic. SUBJECTS: 856 patients who had received local therapy (CO2 laser or cold coagulation) for CIN II or III between 9 and 30 months earlier. INTERVENTION: Each patient had three consecutive cervical smears taken, one with the Ayre's spatula, one with either the Aylesbury, the Rocket or the Multispatula device, and finally one with the Cytobrush. The allocation of which spatula and the order of the first two was randomized. Each patient had a colposcopic examination immediately after the smears were taken. MAIN OUTCOME MEASURES: A comparison of the detection of histologically proven persistent CIN by the Ayre's spatula with the detection of persistent disease by alternative sampling devices. RESULTS: Of the 856 patients 130 had histologically proven persistent CIN. Another 98 had suspicious findings on colposcopy but punch biopsies reported as histologically normal. Of the remaining patients with normal colposcopy 130 were randomly selected to form a control group. The cervical smears from these 358 women were reported. Significantly fewer Ayre's samples contained endocervical cells than Aylesbury samples (47% vs 59%, difference 12%; 95% CI 3%-21%; P less than 0.001), Rocket samples (47% vs 67%; difference 20%, 95% CI; 12%-32%; P less than 0.001) or Multispatula samples (47% vs 76%; difference 29%, 95% CI 19-38%; P less than 0.001). When punch biopsies contained CIN, dyskaryotic cells were seen in 10% of Ayre's samples, 4.3% of Aylesbury samples, 8.3% of Rocket samples, and in no smear taken with the Multispatula. Obtaining a third smear with the Cytobrush did not substantially improve the detection rate of dyskaryosis. Neither the order of use of the spatulas, the form of initial treatment nor the size of the transformation zone had any apparent effect on the cytological detection of persistent CIN. CONCLUSIONS: We recommend that surveillance of patients who have received local ablative therapy for CIN should be by both cytology and colposcopy, and that cytological samples should be obtained using the Ayre's spatula.     

Human papillomavirus type 16 and 18 detection in the management of mild dyskaryosis.

OBJECTIVE: To determine if semi-quantitative human papillomavirus (HPV) types 16 and 18 detection by polymerase chain reaction can increase the sensitivity and specificity of repeat cytology alone for underlying high grade cervical intraepithelial neoplasia (CIN). DESIGN: Prospective randomised study of immediate treatment and surveillance. SETTING: A dedicated colposcopy clinic serving a regional population. SAMPLE: Three hundred and four women with smears reported as mild dyskaryosis. METHODS: Repeat cytology, HPV 16 and 18 tests, and colposcopy were performed at study entry. Women were randomised to either immediate treatment or surveillance with repeated tests at 6 and 12 months. Unless all study smears were negative, women were treated at study exit by large loop excision of the transformation zone. MAIN OUTCOME MEASURES: Sensitivity and specificity of HPV testing for types 16 and 18 in conjunction with cytology for high grade CIN. RESULTS: Combining repeat cytology with HPV 16 and 18 testing had a sensitivity of 94% and a specificity of 26%, a positive predictive value of 71%, and a negative predictive value of 71%, for underlying high grade CIN. If used to secondary screen in conjunction with repeat cytology for mild dyskaryosis, 88% of women would have been referred for colposcopy on the basis of either test being positive. CONCLUSION: Combining repeat cytology and HPV 16 and 18 detection would result in the majority of women being referred for immediate colposcopy. Taken with an overall default rate of 17%, immediate referral of all women with mild dyskaryosis for colposcopic assessment still appears to be a more effective clinical strategy.