Colposcopic Episodes of Care: Referral, Treatment, Follow-Up, and Exit Patterns of Care for Women With Abnormal Pap Smears

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1 GYNAECOLOGY Colposcopic Episodes of Care: Referral, Treatment, Follow-Up, and Exit Patterns of Care for Women With Abnormal Pap Smears Rachel Kupets, MD, 1 Yan Lu, MSc, 2 Danielle Vicus, MD, 1 Lawrence Paszat, MD 2 ; on behalf of The Ontario Cancer Screening Research Network 1 Division of Gynecologic Oncology, Sunnybrook Regional Cancer Centre, University of Toronto, Toronto ON 2 Institute of Clinical Evaluative Sciences, Toronto ON Abstract Objective: To define the patterns of care of women after they have been referred to a colposcopic service. Methods: We carried out this population-based study by linking databases of health care provision for We defined colposcopic episodes of care as a series of colposcopic evaluations beginning at the time of referral for colposcopy because of a new cervical cytology abnormality and continuing until no colposcopy or cytology service had been performed for 365 days. Results: Cytology reports indicating low-grade squamous intraepithelial lesions and atypical squamous cells of uncertain significance account for 88% of referrals of women for colposcopy. Women aged 20 to 29 had the highest rates of referral and treatments. Up to 87% of women referred for low-grade squamous intraepithelial lesions cytology did not require treatment after colposcopic evaluation, while 54% of women referred for high-grade squamous intraepithelial lesions cytology required treatment. The duration of colposcopic episodes of care in which treatment was carried out lasted up to 327 days, with a median three colposcopic evaluations per episode, whereas episodes of care in which no treatment was carried out lasted up to 190 days with a median of one or two colposcopic examinations per episode. Conclusion: Young women aged 20 to 29 have the highest rates of colposcopic services. Women referred because of cytology showing high-grade squamous intraepithelial lesions in whom treatment is not carried out require more extensive follow-up to ensure that lesions are not missed. We recommend the incorporation of colposcopy services into centralized cervical cancer screening programs. J Obstet Gynaecol Can 2014;36(12): Key Words: Colposcopy, patterns of referral, cervical dysplasia Competing Interests: None declared. Received on June 6, 2014 Accepted on June 23, 2014 Résumé Objectif : Définir les profils de soins qui sont offerts aux femmes à la suite de leur orientation vers un service de colposcopie. Méthodes : Nous avons mené cette étude en population générale en liant des bases de données sur l offre de soins de santé pour ce qui est de l année Nous avons défini le terme «épisodes de soins colposcopiques» comme étant une série d évaluations colposcopiques débutant au moment de l orientation en colposcopie (en raison de la constatation d une nouvelle anomalie cervicale révélée par cytologie) et se poursuivant jusqu à ce que la dernière intervention de colposcopie ou de cytologie remonte à 365 jours ou plus. Résultats : Les rapports de cytologie indiquant la présence de lésions malpighiennes intra-épithéliales de bas grade histologique et de cellules malpighiennes atypiques de signification indéterminée sont à l origine de 88 % des orientations en colposcopie. Les femmes âgées de 20 à 29 ans comptaient les taux les plus élevés d orientation et de traitement. Jusqu à 87 % des femmes orientées en colposcopie en raison d une cytologie indiquant la présence de lésions malpighiennes intra-épithéliales de bas grade histologique n ont pas nécessité la mise en œuvre d un traitement à la suite de l évaluation colposcopique, tandis que 54 % des femmes orientées en colposcopie en raison d une cytologie indiquant la présence de lésions malpighiennes intra-épithéliales de haut grade histologique ont nécessité un traitement. Les épisodes de soins colposcopiques dans le cadre desquels un traitement a été administré ont été d une durée pouvant atteindre 327 jours (médiane : trois évaluations colposcopiques par épisode), tandis que les épisodes de soins colposcopiques dans le cadre desquels aucun traitement n a été administré ont été d une durée pouvant atteindre 190 jours (médiane : une ou deux évaluations colposcopiques par épisode). Conclusion : Les jeunes femmes âgées de 20 à 29 ans comptaient les taux les plus élevés de services colposcopiques. Les femmes orientées en colposcopie en raison d une cytologie indiquant la présence de lésions malpighiennes intra-épithéliales de haut grade histologique qui ne font pas ensuite l objet d un traitement nécessitent la mise en œuvre d un suivi plus exhaustif, de façon à ce que l on puisse s assurer que des lésions ne passent pas inaperçues. Nous recommandons l intégration des services de colposcopie aux programmes centralisés de dépistage du cancer du col utérin. DECEMBER JOGC DÉCEMBRE

2 Gynaecology INTRODUCTION Colposcopy is a definitive step in the management of women with abnormal cervical cytology. If colposcopic interventions are performed appropriately, the risk of cervical cancer in women at high risk is greatly reduced. The Society of Obstetricians and Gynaecologists of Canada and the American Society of Colposcopy and Cervical Pathology have published guidelines on the colposcopic management of cervical dysplasia. 1,2 Their intention is to maximize the effectiveness of colposcopy and related treatment. Evaluation of the use of colposcopy with or without related treatment is necessary to identify components of the process that can be improved, in order to maximize effectiveness. In this study, we have evaluated the delivery of colposcopy services and treatment for cervical dysplasia among women with a new cytologic diagnosis of cervical dysplasia during 2010 in the province of Ontario. METHODS This study was conducted at the Institute for Clinical Evaluative Sciences in Toronto. This institute holds databases of health services use and disease registries that cover the entire population of permanent residents of Ontario. We identified all women age 14 years during 2010 from the Registered Persons Database, a roster of the beneficiaries of the single universal public insurer for health services. Each person has an encrypted version of her health insurance number, which is also attached to all individual electronic records of service delivery and other health databases. Among these women, we identified those with cytological reports of atypical squamous cells of uncertain significance, low-grade squamous intraepithelial lesions, or high-grade squamous intraepithelial lesions in the province-wide database of cervical samples collected in community settings (Cytobase) in ABBREVIATIONS ASCCP CIHI CIN IQR OHIP SD American Society of Colposcopy and Cervical Pathology abnormal squamous cells of uncertain significance Canadian Institute for Health Information cervical intraepithelial neoplasia high-grade squamous intraepithelial lesion interquartile range low-grade squamous intraepithelial lesion Ontario Health Insurance Plan standard deviation From the Ontario Health Insurance Plan physician billings database, we identified women with one or more colposcopy billing claims in the six months following the date of the cytology sample collection. We extracted further Cytobase reports, colposcopy billing claims, and billing claims for ablative and excisional cervical treatments from OHIP and from the Canadian Institute for Health Information databases on procedures conducted on hospital premises. We defined a colposcopic episode of care for a new cytologic diagnosis of cervical dysplasia (without an abnormality in the preceding12 months) as beginning with the date of collection of the sample showing abnormal cytology and ending on the date of any cytology report, colposcopy billing claim, or cervical treatment procedure that was followed by an interval of 365 days without further cytology report, colposcopy claim or treatment. If a colposcopic episode of care included the woman undergoing hysterectomy, she was excluded from the analysis. Women were also excluded for prior hysterectomy (Canadian Institute for Health Information or OHIP) and/or prior diagnosis of cervical or uterine cancer in the Ontario Cancer Registry. We calculated the counts and rates of colposcopy and colposcopic episodes of care per eligible women as well as the mean ± standard deviation (SD) and median (IQR) number of colposcopic examinations per overall episode, and among episodes stratified as including or excluding cervical treatment. Colposcopic episodes of care were stratified by age and by the,, or cytologic diagnosis prompting the colposcopy. Ethics approval fore the study was provided by the Research Ethics Board of Sunnybrook Health Sciences Centre. RESULTS We identified women aged 14 years who began a new colposcopic episode of care in 2010 with a cytologic diagnosis of,, or ; 2638 (12.8%) had, 9129 (44.8%) had, and 8600 (42%) had. Women aged 20 to 29 accounted for 41% of the study population. cytology was less common in the 14 to 24 age category and more frequent in the 30 to 39 year category. was the most common cytologic diagnosis in the 14 to 29 age group, while was more common in the 40 age group (Table 1). Among all subjects, 4214 (20.7%) underwent one or more treatments during the colposcopic episode of care, with follow-up to December 31, Of those with cytology, 53.5% underwent treatment, while 16.3% of 1080 DECEMBER JOGC DÉCEMBRE 2014

3 Colposcopic Episodes of Care: Referral, Treatment, Follow-Up, and Exit Patterns of Care for Women With Abnormal Pap Smears Table 1. Index cervical cytology diagnosis for initiation of colposcopic episode of care and rates of colposcopic episodes of care per women by patient age n = 8600 n = 9129 n = to (34) 457 (59) 52 (7) to (37) 2396 (54) 388 (9) to (39) 1800 (46) 360 (15) to (34) 2070 (43) 850 (18) to (47) 1393 (40) 481 (14) to (54) 723 (36) 212 (10) to (57) 248 (33) 76 (10) (61) 42 (27) 19 (12) 155 Number of colposcopies per episode of care Mean (SD) 1.83 (1.08) 1.93 (1.14) 2.42 (1.37) Median (IQR) 1 (1 to 2) 2 (1 to 3) 2 (1 to 3) Mean (SD) (174.51) (182.08) (183.97) Median (IQR) 58 (0 to 293) 126 (0 to 323) 224 (52 to 374) Total those with cytology and 14.2% of those with cytology underwent treatment. Most cervical treatment was excisional, but the proportion varied according to age: 56% of women aged 14 to 19, 79% of those aged 30 to 39, and over 90% of those aged 60 to 69 had excisional treatment. Of women aged 14 to 19, 27% underwent treatment when referred because of cytology, but up to 60% of women aged 20 and older had treatment when referred for cytology (Tables 2 and 3). The number of colposcopies performed in each episode of care that included treatment varied slightly according to the grade of cytologic diagnosis. For episodes of care that began because of cytology, the median number of colposcopies was three, although 2.5% underwent more than five; for episodes of care that began with and cytology, and included treatment, the median number of colposcopies was two, again with 2.5% undergoing more than five. Colposcopic episodes of care without treatment had a similar number of colposcopic examinations (women referred for cytology had a median of 2 colposcopies, and > 2.5% underwent more than 5, while women referred for cytology had a median of 1 colposcopy with 2.5% undergoing more than 4) (Tables 2 and 3). The duration of colposcopic episodes of care that included one or more cervical treatments was much longer than those without treatment. Women with cytology who underwent treatment had a median episode of care duration of 327 days, compared with 190 days for women without treatment; those with who were treated had a median of 245 days, compared with 84 days for those without treatment; and women with who were treated had a median duration of 210 days, compared with one single day for those without treatment (Tables 2, 3, and 4). DISCUSSION We determined that 87% of colposcopies were initiated for the minor cytologic abnormalities of and. In 2010, these abnormalities accounted for new colposcopic episodes of care out of the total episodes. Forty percent of the study population (8114 women) consisted of women less than 30 years of age. Furthermore, of all the women referred to colposcopy for cytology, only 14% (2802 women) underwent treatment for a lesion. This finding of high numbers of referrals for and low treatment rates underscores the consumption of colposcopic resources by referrals that are unlikely to show high- grade cervical dysplasia. Recent evidence indicates that the five-year risk of developing CIN 3 or higher in women with cytology who are HPV-positive is only 6%, and only 2% in women with cytology who are HPV-negative; the risk of CIN 3 or higher in women with cytology is 2.6%, regardless of HPV status. 1 DECEMBER JOGC DÉCEMBRE

4 Gynaecology Table 2. Colposcopic episodes of care with excisional treatment for cervical dysplasia by age and index cytologic diagnosis n = 982 n = 1052 n = to (6) 22 (5) 8 (15) 20 to (8) 216 (9) 126 (32) 25 to (12) 184 (10) 250 (45) 30 to (14) 300 (14) 415 (49) 40 to (13) 192 (14) 258 (54) 50 to (10) 107 (15) 108 (51) 60 to (10) 25 (10) 31 (41) (11) 6 (14) 8 (42) Number of colposcopies per episode of care Mean (SD) 2.43 (1.37) 2.39 (1.38) 2.54 (1.38) Median (IQR) 2 (1 to 3) 2 (1 to 3) 2 (1 to 3) Mean (SD) (179.2) (175.9) (182.7) Median (IQR) 208 (63 to 374) 214 (70 to 384) 240 (70 to 401) Table 3. Colposcopic episodes of care with ablative treatment for cervical dysplasia by age and index cytologic diagnosis n = 335 n = 433 n = to 19 7 (3) 24 (5) 6 (12) 20 to (5) 125 (5) 35 (9) 25 to (4) 99 (6) 49 (9) 30 to (5) 90 (4) 74 (9) 40 to (4) 65 (5) 33 (7) 50 to (2) 23 (3) 7 (3) 60 to 69 5 ( 1) 7 (3) 5 ( 6) 70 5 ( 5) 0 (0) 5 ( 3) Number of colposcopies per episode of care Mean (SD) 2.52 (1.49) 2.67 (1.60) 3.22 (1.64) Median (IQR) 2 (1 to 4) 2 (1 to 4) 3 (2 to 4) Mean (SD) (179.6) (188.4) (187.7) Median (IQR) 210 (42 to 378) 245 (70 to 400) 327 (133 to 472) 1082 DECEMBER JOGC DÉCEMBRE 2014

5 Colposcopic Episodes of Care: Referral, Treatment, Follow-Up, and Exit Patterns of Care for Women With Abnormal Pap Smears Table 4. Colposcopic episodes of care in which no treatment was carried out for index cytologic abnormality n = 7283 n = 7644 n = to (91) 411 (90) 38 (73) 20 to (87) 2055 (86) 227 (59) 25 to (84) 1517 (84) 261 (47) 30 to (81) 1680 (81) 361 (42) 40 to (83) 1136 (82) 190 (40) 50 to (88) 593 (82) 97 (46) 60 to (88) 216 (87) 42 (55) (86) 36 (86) 10 (53) Number of colposcopies per episode of care Mean (SD) 1.72 (0.96) 1.83 (1.04) 2.17 (1.23) Median (IQR) 1 (1 to 2) 1 (1 to 2) 2 (1 to 3) Mean (SD) (169.7) (179.4) (178.1) Median (IQR) 0 (0 to 266) 84 (0 to 305) 190 (0 to 243) Given the low underlying risk of high-grade lesions in this group, physicians should use strategies that will result in referral of the women most likely to have serious lesions on the cervix for colposcopy while managing the remainder conservatively. Recent ASCCP guidelines recommend that HPV co-testing should be performed in women with cytology in an effort to reduce the number of referrals; they also recommend that women aged 21 to 24 should be followed with repeat cytology in 12 months rather than be referred for colposcopy. 2 Similarly, it is acceptable to repeat smears showing cytology in 12 months. 2 Our recent research has found that 48% of cytology and 68% of cytology will revert to normal when repeated within a six-month interval, supporting a conservative referral rate for colposcopy. It is also important to note that, in our cohort, 54% of women with cytology underwent treatment for a lesion that was presumably identified at colposcopy. This finding is in keeping with studies which found that cytology is associated with a 56% positive predictive value for finding dyplasia. 3 In this study we clustered the delivery of colposcopic care into colposcopic episodes of care. We found that for episodes of care that began with or cytology and in which treatment was carried out, there was a median of two colposcopic examinations. When an episode of care began with cytology, a median of two to three colposcopic examinations were carried out when treatment was carried out. The duration of episodes of care in which treatment was carried out was longest for women with cytology and shortest for cytology. For all diagnoses, however, the median duration of care was less than one year. When treatment is carried out for a cervical lesion, women should be discharged from a colposcopy clinic only when it is likely that the lesion has been eradicated. Current guidelines from the Society of Canadian Colposcopists recommend two follow-up examinations at six-month intervals after treatment, whereas the ASCCP now recommends an HPV test of cure at 12 months after treatment and no colposcopic examinations. The latter approach promises to be the more efficient, because HPV-negative status after treatment has a 100% negative predictive value for residual disease, and women with persistent HPV-positive testing have a 15% likelihood of recurrent or persistent dyplasia with normal cervical cytology and a 50% likelihood with abnormal cytology. 2,4,5 In this study we also evaluated colposcopic episodes of care in which no treatment was carried out for an index finding of cervical dysplasia. This is of particular interest in cases in which episodes of care were initiated for cytology. In our study population, 46% of women referred because of cytology did not have treatment for dysplasia. DECEMBER JOGC DÉCEMBRE

6 Gynaecology It is difficult to determine the correct follow-up in circumstances in which a cytologic abnormality has been identified, but there is no corresponding lesion on the cervix. This is particularly pertinent for cytology. Although women in our study were followed for a median of 200 days and two colposcopic examinations, it is possible that cervical lesions may have been missed in this limited follow-up. Previous studies have found that colposcopy has a sensitivity of 98% and specificity of 45% for the detection of CIN 2 lesions or higher. 6 It has also been demonstrated that the sensitivity of colposcopy to detect CIN 2 lesions or higher increases when two or more biopsies are carried out. 6 It is important to determine what happens to women who have an unsatisfactory colposcopic examination and how many follow-up examinations are required to ensure that no lesion is being missed. The current ASCCP guidelines recommend that when no abnormality is detected on colposcopy, further colposcopy and cytology should be carried out at six-month intervals for two years. 2 If these recommendations were to be followed, then a total of four colposcopic examinations would be carried out; this is twice as many as are currently performed. We do not have adequate data to determine if the current pattern of practice misses a clinically significant proportion of high-risk lesions. Further research into this subgroup of patients is required to determine what the screening patterns are for them, and whether or not they are eventually found to have an abnormality that requires treatment. Attention should be focused on the proportion of patients who are eventually found to have CIN 3 lesions or higher. In this study, there was a clear preference for excisional techniques for treatment over ablative techniques. This may be due to limited access to laser in outpatient settings, whereas loop electrical excision procedure and electrocautery units are more readily available. The rates for eradicating cervical dysplasia are the same for both treatment modalities. 7 CONCLUSION Colposcopy is a crucial step in the evaluation of women with cervical cytologic abnormalities leading to the eradication of immediate precursors of invasive disease. While cervical cancer screening programs begin with a focus on women receiving timely and regular Pap smears, colposcopy should be considered as a continuation of the spectrum of cervical cancer prevention. In order to provide the best care possible within a colposcopy program, we should determine the appropriate patient population for colposcopy, the appropriate duration of follow-up for an episode of care, and when it is appropriate to discharge women from colposcopic care. The appropriate follow-up of women who have had a high-grade abnormality on Pap testing but no immediate identification of a lesion should be defined, because these women can be at significant risk for eventual identification of a high-grade lesion of the cervix. Future endeavours should integrate colposcopy into centralized screening programs in which evaluation of care is assessed to determine if care is delivered in accordance with evidence-based guidelines. REFERENCES 1. Katki HA, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T, et al. Five-year risks of CIN 2+ and CIN 3+ among women with HPV-positive and HPV-negative Pap results. J Low Genit Tract Dis 2013;17(5 Suppl 1):S Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, et al updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol 2013;121(4): Saha R, Thapa M. Correlation of cervical cytology with cervical histology. Kathmandu Univ Med (KUMJ) 2005;3(3): Bentley J. Colposcopic management of abnormal cervical cytology and histology. J Obstet Gynaecol Can 2012;34(12): Verguts J, Bronselaer B, Donders G, Arbyn M, Van Eldere J, Drijkoningen M, et al. Prediction of recurrence after treatment for high-grade cervical intraepithelial neoplasia: the role of human papillomavirus testing and age at conisation. BJOG 2006;113(11): Gage JC, Hanson VW, Abbey K, Dippery S, Gardner S, Kubota J, et al. Number of cervical biopsies and sensitivity of colposcopy. Obstet Gynecol 2006;108(2): Raju KS, Henderson E, Trehan A. A study comparing LETZ and CO 2 laser treatment for cervical intra epithelial neoplasia with and without associated human papilloma virus. Eur J Gynaecol Oncol 1995;16(2): DECEMBER JOGC DÉCEMBRE 2014