- Email: [email protected]
Management of the mildly abnormal Pap smear: A conservative approach
GYNECOLOGIC
ONCOLOGY
22, 149-153
(1985)
Management of the Mildly Abnormal Pap Smear: A Conservative Approach’ MARK Division
S. BROWN, M.D. ,’ AND GEORGE L. PHILLIPS, JR., M.D. of Gynecologic-Oncology, Fitzsimons Army Medical
Department of Obstetrics Center, Aurora, Colorado
and Gynecology, 80045
Received June 27, 1984 Follow-up and management of the mildly abnormal Pap smear has been the subject of controversy in the medical literature. At Fitzsimons Army Medical Center, patients with initial Pap smears reported as “inflammatory atypia” or mild dysplasia were treated with specific therapy for vaginitis and/or cervicitis. Follow-up smears were performed 6 to 8 weeks later. Of the above groups, 80 and 58%, respectively, were negative on repeat smear. A third group of patients with Pap smears reported as consistent with human papillomavirus (HPV) were not treated but had repeat smears performed at 6 to 8 weeks. Of these, 76.4% reverted to normal. The results of the colposcopically directed cervical biopsies obtained on patients with persistently abnormal smears are reported. These findings support a conservative plan for follow-up of mildly abnormal Pap smears. 0 1985 Academic Press. Inc.
INTRODUCTION
Proper evaluation, treatment, and follow-up of Pap smears showing atypia and mild dysplasia have been controversial. In 1972, Nyirjesy reported atypical Pap smears among 1.6% of his patients [I]. Following specific treatment, 85% of these patients reverted to normal. Based upon this, Nyirjesy recommended that, if a normal smear were obtained on the first follow-up visit, the patient could be followed with repeat smears every 3 months. Only those patients with persistent atypia were subjected to biopsies. Other authors have differed with this view. Hulka recommended follow-up for 18 months or three straight atypical smears prior to biopsy [2]. Koss, on the other hand, recommended immediate colposcopically directed biopsies [3]. The present paper reports experience with a protocol similar to Njirjesy. atypia” and “mild dysplasia” were subject Smears reported as “inflammatory to a “treat and repeat” protocol prior to biopsy. In addition, the management of Pap smears reported as consistent with HPV has become problematic for the practitioner. Though an association (not necessarily ’ The opinions asserted in this article are those of the authors and are not to be interpreted as official views of the Department of Defense or the Department of the Army. ’ To whom reprint requests should be addressed at: Department of Obstetrics and Gynecology, Ireland Army Hospital, Fort Knox, Ky. 40121. 149 0090-8258/85
$1.50
Copyright 0 1985 by Academic Press, Inc. All rights of reproduction in any form reserved.
150
BKOWN
AND
PHILLIPS
causative) has been shown between HPV infections and cervical intraepithelial neoplasia [4-91, no specific recommendations have been made regarding proper Pap smear follow-up in these cases. This paper again explores a conservative approach to this problem. MATERIALS
AND METHODS
Outpatient records of 241 patients from Fitzsimons Army Medical Center, Aurora, Colorado, from 1 July 1981 to 31 December 1983, were reviewed. Patients were selected for record review if routine Pap smear was reported as mildly abnormal, as described below. Excluded from this study were the patients who had a prior history of abnormal Pap smears or those whose cervices had previously been treated with cryosurgery, electrocautery, laser vaporization, or cone biopsy. Patients were then divided into three groups. Group I patients were those whose Pap smears were reported unequivocally as “mild dysplasia.” Patients with the report stating “mild to moderate” dysplasia, “dysplasia unable to grade,” or suggestive of an even more serious lesion were referred directly for colposcopy. Group II patients were those whose Pap smears were reported as “inflammatory atypia” or “reactive atypia” without dysplasia. Omitted from this group were patients whose Pap smears showed reactive or inflammatory changes only, without mention of atypia. Both Group I and Group II patients were treated for lo-21 days with appropriate intravaginal medications. These consisted of triple sulfa cream in most cases, but occasionally consisted of miconazole nitrate 2% cream and dienestrol cream in selected cases. All patients were then rescreened with Pap smears at 6- to Sweek intervals. If repeat cytology indicated persistence of the original finding or progression of the lesion, patients were immediately referred for colposcopically directed biopsies. If, however, repeat cytology were negative, the patients continued to be followed at 6- to 12-month intervals by Pap smear and pelvic examination alone. Group III patients were those whose Pap smears were reported as “koilocytosis,” “koilocytotic atypia,” or “consistent with condyloma acuminata.” If other abnormalities were seen with these findings, the patients were placed in Group I or Group II or referred for colposcopy, as appropriate. If these findings alone were reported, a repeat smear was performed in 6-12 weeks without interim treatment. In all cases, a description of the previous Pap smear result was provided on the follow-up cytology request sheet to alert cytologic screeners and minimize false negative reports on repeat smears. RESULTS
Group I. Of 86 patient charts reviewed, 48 Pap smears (58%) were noted to have reverted to normal. Of these 48, further follow-up smears were noted on 26 patients. All remained negative. Of the remaining 38 patients, follow-up smears showed persistent mild dysplasia in 22 (25.6%), inflammatory atypia in 11 (12.7%), koilocytosis in 4 (4.6%), and moderate dysplasia in a single patient (1.1%). All of these patients subsequently underwent colposcopically directed biopsies.
ABNORMAL
PAP
SMEAR
MANAGEMENT
151
Biopsy results showed a variety of lesions. Koilocytosis only was the most frequent histologic diagnosis, reported in 17 of 38 patients (44.7%). The next most common lesion was CIN III, noted in 11 of 38 patients (28.9%). CIN I and CIN II were diagnosed in 15.8% and 10.5% of patients, respectively. Group ZZ. Of the 104 patients in this group, 84 (80.1%) reverted to normal on follow-up smears. Of the remaining 20 patients, 10 (9.6%) persisted with smears reported as inflammatory atypia. Inflammatory atypia with koilocytosis was reported on three smears (2.9%). Mild dysplasia with koilocytosis was reported on three smears (2.9%). Two smears (1.9%) were reported as consistent with condyloma acuminata. One smear (0.9%) was reported as dysplasia, unable to grade, and one smear (0.9%) was reported as moderate dysplasia. Again, all patients with findings consistent with persistent or progressive lesions underwent colposcopically directed biopsies which demonstrated a variety of lesions. Koilocytosis was seen in 6 of 20 patients (30%) and CIN III was noted in an identical number. CIN II was diagnosed in 4 patients (20%), as was CIN I. Group ZZZ. Fifty-one patients had Pap smears consistent with HPV infection. Follow-up smears were negative in 39 (76.4%). Of the remaining 12 patients, koilocytosis was seen on repeat smear in 11 (21%). The remaining patient (2%) showed mild dysplasia with koilocytosis. These 12 patients underwent colpostopically directed biopsies. Koilocytosis alone was confirmed by biopsy in 11 of 12 patients (92%). One patient (8%) had CIN I noted on biopsy. All patients were then treated with cryotherapy. DISCUSSION A review of the literature reveals a variety of recommendations for follow-up and management of atypical or mildly dysplastic Pap smears. The “treat and repeat” system of Nyitjesy [I] followed here has considerable support in the literature. Hulka reported that if a smear reverted to normal from Class II, the probability that subsequent smears would be negative was high (80-92%) [2]. In addition, she showed that the longer the interval of time allowed for healing from the presumed inflammatory insult, the larger the percentage of regression to normal. Hall and Walton’s work would support this conservative approach [lo]. In dysplasia regressed in 62.2% of patients with no therapy their study, “slight” (except for biopsies performed). The abnormality persisted in 24.4% and progressed in only 13.4%. Buckley et al. [ll] and Meisels [I21 agreed that mild dysplasia may be confused with inflammatory changes and recommend a treat and repeat plan of follow-up. Their recommendations are based upon the fact that the most severe histological lesion can be predicted in about 80% of cases from this cytological smear [I31 and that, in their experience, false-negative smears are rare [12,14]. Other authors disagree. Koss noted that Nyijesy showed carcinoma in situ in one-quarter of his patients with persistent atypia [3]. Figge and associates concurred [14]. Koss further maintained that repeat smears are negative in 30-
152
BROWN
AND
PHILLIPS
40% of patients with CIS. Rubio found a similar figure in an independent investigation [15]. Rylander showed similar findings in a study of invasive cervical cancer [16]. Twenty-three patients had follow-up initiated by cytology. Evaluation was discontinued, though, when follow-up cytology was negative. All were later diagnosed as invasive cervical cancer. For these reasons, Koss and others believe that a repeat smear after a Class II Pap smear is unreliable. Instead, they feel that colposcopy is mandatory [ 17,181. The present study following the recommendations of Nyirjesy showed regression rates of 58% for patients with mild dysplasia and 80.1% for patients with inflammatory atypia. These findings support the efficacy of the treat and repeat approach. Considering the large number of Pap smears performed in many centers and the considerable cost of colposcopy and biopsy, the follow-up procedure of Nyirjesy seems a rational approach. In addition, patient discomfort and anxiety would be minimized. Colposcopically directed biopsies on patients with persistently abnormal smears, however, showed CIN III in 30% of patients. Patients with persistently abnormal smears or in whom follow-up is questionable, should be promptly evaluated with colposcopy. However, in no case was an invasive carcinoma of the cervix missed by this conservative approach. Recommendations concerning follow-up and therapy of HPV infections of the cervix (as suggested by Pap smear) are unclear. Pap smears will show koilocytosis in l-2% of cases [4,7] and 70% of mild dysplasia can be reclassified as koilocytosis on reexamination [7]. HPV infections may coexist with dysplastic and neoplastic lesions in 25.6 to 91% of cases [7,81. Such findings have led to recommendations that HPV infections be evaluated and treated as are conventional forms of CIN
[51. In the present study, 76.4% of patients with Pap smears consistent with HPV infection regressed to negative without intervening therapy. Meisels had previously reported a 68.39% regression rate [7]. Whether this reflects regression of HPV infection or the incorporation of the viral genome into the cervical epithelium is unknown. These figures do, however, support a conservative approach of continued cytological evaluation for patients with findings suggestive of HPV on a single Pap smear. Because prospective studies are lacking and the absence of HPV cannot be guaranteed, patients with normal repeat smears should continue close follow-up. Patients with persistence or progression of findings suggestive of HPV infection or patients in whom follow-up cannot be guaranteed, should have further evaluation with colposcopically directed biopsies to rule out coexistent CIN. Though 92% of the patients who underwent colposcopically directed biopsies in the present study were noted to have koilocytosis only on histologic diagnosis, a strong, possibly etiologic, association of HPV with CIN warrants further immediate evaluation for these patients. CONCLUSION
(1) For patients with no history of previous cervical pathology or treatment, an initial conservative approach to mildly abnormal Pap smears is justified. If atypia or mild dysplasia were noted on cytologic evaluation, regression to normal
ABNORMAL
PAP SMEAR MANAGEMENT
153
occurred in 80.1 and 58%, respectively, after administration of specific intravaginal medication. (2) For patients with persistently abnormal smears or for those patients in whom follow-up cannot be guaranteed, prompt referral for colposcopy is recommended, as 30% of such patients demonstrated CIN III on colposcopically directed biopsies in the present study. (3) In no case was invasive carcinoma of the cervix missed by the conservative approach taken. (4) For patients with a single Pap smear suggestive of HPV infection, an initial conservative approach may be taken, as 76.4% of patients showed no abnormality on follow-up smear. The patients with persistently abnormal smears should be evaluated by colpostopically directed biopsies and treated appropriately, though CIN I was the most severe histologic lesion noted in the present study. (5) Further long-term prospective studies concerning HPV infections are needed before final recommendations concerning management can be made. REFERENCES 1. Nyitjesy, I. Atypical or suspicious cervical smears: An aggressive diagnostic approach, JAMA 222, 691-693
(1972).
Hulka, B. S. Cytologic and histologic outcome following an atypical cervical smear, Amer. J. Obstet. Gynecol. 101, 190-199 (1968). 3. Koss, L. G. Dysplasia: A real concept or a misnomer? O&et. Gynecol. 51, 374-379 (1978). 4. Ludwig, M. E., Lowell, D. M., and Livolsi, V. A. Cervical condylomatous atypia and its relationship to cervical neoplasia, Amer. J. Clin. Pathol. 76, 255-262 (1981). 5. Kaufman, R., Koss, L. G., Kurman, R. J., et al. Statement of caution in the interpretation of papillomavirus-associated lesions of the epithelium of the uterine cervix, Amer. J. Obstet. 2.
Gynecol.
146, 125.
6. Boon, M. E., and Fox, C. H. Simultaneous condyloma acuminatum and dysplasia of the uterine cervix, Acta Cytol. 25, 393-399 (1981). 7. Meisels, A., and Morin, C. Human papillomavirus and cancer of the uterine cervix, Gynecol. Oncol. 12, Slll-S123 (1981). 8. Reid, R., Stanhope, C. R., Herschman, B. R., et al. Genital warts and cervical cancer. I. Evidence of an association between subclinical papillomavirus infection and cervical malignancy, Cancer 50, 377-387 (1982). 9. Syjanen, K. L. Current concepts of human papillomavirus infections in the genital tract and their relationship to intraepithelial neoplasia and squamous cell carcinoma, Obstet. Gynecol. Surv.
39, 252-265
(1984).
10. Hall, J. E., and Walton, L. Dysplasia of the cervix: A prospective study of 206 cases, Amer. .I. Obstet.
Gynecol.
100, 662-668
(1968).
11. Buckley, C. H., Butler, E. B., and Fox, H. Cervical intraepithelial 35, l-13
neoplasia, J. C/in. Pathol.
(1982).
12. Meisels, A. Dysplasia and carcinoma of the uterine cervix. IV. A correlated cytologic and histologic study with special emphasis on vaginal microbiology, Acta Cyrol. 13, 224-231 (1969). 13. Husain, 0. A. N., Butler, E. B., Evans, D. M. D., ef al. Quality control in cervical cytology, J. Clin.
Pathol.
27, 935-944
(1974).
14. Figge, D. C., Bennington, J. L., and Schweid, A. I. Cervical cancer after initial negative and atypical vaginal cytology, Amer. J. Obstet. Gynecol. 108, 422-428 (1970). 15. Rubio, C. A. The false negative smear (letter to the editor), Amer. J. Obstet. Gynecol. 119, 273 (1974).
16. Rylander, E. Cervical cancer in women belonging to a cytologically screened population, Acta Obstet.
Gynecol.
Stand.
55, 361-366
(1976).
Feldman, M. J., Linzey, E. M., Srebnik, E., et al. Abnormal cervical cytology in the teen-ager: A continuing problem, Amer. J. Obstet. Gynecol. 126, 418-421 (1976). 18. Koss, L. G., and Coleman, D. V. Epidermoid carcinoma of the uterine cervix and related precancerous lesions, in Advances in clinical cytology, Butterworths, London, pp. 285-393 (1981). 17.
ONCOLOGY
22, 149-153
(1985)
Management of the Mildly Abnormal Pap Smear: A Conservative Approach’ MARK Division
S. BROWN, M.D. ,’ AND GEORGE L. PHILLIPS, JR., M.D. of Gynecologic-Oncology, Fitzsimons Army Medical
Department of Obstetrics Center, Aurora, Colorado
and Gynecology, 80045
Received June 27, 1984 Follow-up and management of the mildly abnormal Pap smear has been the subject of controversy in the medical literature. At Fitzsimons Army Medical Center, patients with initial Pap smears reported as “inflammatory atypia” or mild dysplasia were treated with specific therapy for vaginitis and/or cervicitis. Follow-up smears were performed 6 to 8 weeks later. Of the above groups, 80 and 58%, respectively, were negative on repeat smear. A third group of patients with Pap smears reported as consistent with human papillomavirus (HPV) were not treated but had repeat smears performed at 6 to 8 weeks. Of these, 76.4% reverted to normal. The results of the colposcopically directed cervical biopsies obtained on patients with persistently abnormal smears are reported. These findings support a conservative plan for follow-up of mildly abnormal Pap smears. 0 1985 Academic Press. Inc.
INTRODUCTION
Proper evaluation, treatment, and follow-up of Pap smears showing atypia and mild dysplasia have been controversial. In 1972, Nyirjesy reported atypical Pap smears among 1.6% of his patients [I]. Following specific treatment, 85% of these patients reverted to normal. Based upon this, Nyirjesy recommended that, if a normal smear were obtained on the first follow-up visit, the patient could be followed with repeat smears every 3 months. Only those patients with persistent atypia were subjected to biopsies. Other authors have differed with this view. Hulka recommended follow-up for 18 months or three straight atypical smears prior to biopsy [2]. Koss, on the other hand, recommended immediate colposcopically directed biopsies [3]. The present paper reports experience with a protocol similar to Njirjesy. atypia” and “mild dysplasia” were subject Smears reported as “inflammatory to a “treat and repeat” protocol prior to biopsy. In addition, the management of Pap smears reported as consistent with HPV has become problematic for the practitioner. Though an association (not necessarily ’ The opinions asserted in this article are those of the authors and are not to be interpreted as official views of the Department of Defense or the Department of the Army. ’ To whom reprint requests should be addressed at: Department of Obstetrics and Gynecology, Ireland Army Hospital, Fort Knox, Ky. 40121. 149 0090-8258/85
$1.50
Copyright 0 1985 by Academic Press, Inc. All rights of reproduction in any form reserved.
150
BKOWN
AND
PHILLIPS
causative) has been shown between HPV infections and cervical intraepithelial neoplasia [4-91, no specific recommendations have been made regarding proper Pap smear follow-up in these cases. This paper again explores a conservative approach to this problem. MATERIALS
AND METHODS
Outpatient records of 241 patients from Fitzsimons Army Medical Center, Aurora, Colorado, from 1 July 1981 to 31 December 1983, were reviewed. Patients were selected for record review if routine Pap smear was reported as mildly abnormal, as described below. Excluded from this study were the patients who had a prior history of abnormal Pap smears or those whose cervices had previously been treated with cryosurgery, electrocautery, laser vaporization, or cone biopsy. Patients were then divided into three groups. Group I patients were those whose Pap smears were reported unequivocally as “mild dysplasia.” Patients with the report stating “mild to moderate” dysplasia, “dysplasia unable to grade,” or suggestive of an even more serious lesion were referred directly for colposcopy. Group II patients were those whose Pap smears were reported as “inflammatory atypia” or “reactive atypia” without dysplasia. Omitted from this group were patients whose Pap smears showed reactive or inflammatory changes only, without mention of atypia. Both Group I and Group II patients were treated for lo-21 days with appropriate intravaginal medications. These consisted of triple sulfa cream in most cases, but occasionally consisted of miconazole nitrate 2% cream and dienestrol cream in selected cases. All patients were then rescreened with Pap smears at 6- to Sweek intervals. If repeat cytology indicated persistence of the original finding or progression of the lesion, patients were immediately referred for colposcopically directed biopsies. If, however, repeat cytology were negative, the patients continued to be followed at 6- to 12-month intervals by Pap smear and pelvic examination alone. Group III patients were those whose Pap smears were reported as “koilocytosis,” “koilocytotic atypia,” or “consistent with condyloma acuminata.” If other abnormalities were seen with these findings, the patients were placed in Group I or Group II or referred for colposcopy, as appropriate. If these findings alone were reported, a repeat smear was performed in 6-12 weeks without interim treatment. In all cases, a description of the previous Pap smear result was provided on the follow-up cytology request sheet to alert cytologic screeners and minimize false negative reports on repeat smears. RESULTS
Group I. Of 86 patient charts reviewed, 48 Pap smears (58%) were noted to have reverted to normal. Of these 48, further follow-up smears were noted on 26 patients. All remained negative. Of the remaining 38 patients, follow-up smears showed persistent mild dysplasia in 22 (25.6%), inflammatory atypia in 11 (12.7%), koilocytosis in 4 (4.6%), and moderate dysplasia in a single patient (1.1%). All of these patients subsequently underwent colposcopically directed biopsies.
ABNORMAL
PAP
SMEAR
MANAGEMENT
151
Biopsy results showed a variety of lesions. Koilocytosis only was the most frequent histologic diagnosis, reported in 17 of 38 patients (44.7%). The next most common lesion was CIN III, noted in 11 of 38 patients (28.9%). CIN I and CIN II were diagnosed in 15.8% and 10.5% of patients, respectively. Group ZZ. Of the 104 patients in this group, 84 (80.1%) reverted to normal on follow-up smears. Of the remaining 20 patients, 10 (9.6%) persisted with smears reported as inflammatory atypia. Inflammatory atypia with koilocytosis was reported on three smears (2.9%). Mild dysplasia with koilocytosis was reported on three smears (2.9%). Two smears (1.9%) were reported as consistent with condyloma acuminata. One smear (0.9%) was reported as dysplasia, unable to grade, and one smear (0.9%) was reported as moderate dysplasia. Again, all patients with findings consistent with persistent or progressive lesions underwent colposcopically directed biopsies which demonstrated a variety of lesions. Koilocytosis was seen in 6 of 20 patients (30%) and CIN III was noted in an identical number. CIN II was diagnosed in 4 patients (20%), as was CIN I. Group ZZZ. Fifty-one patients had Pap smears consistent with HPV infection. Follow-up smears were negative in 39 (76.4%). Of the remaining 12 patients, koilocytosis was seen on repeat smear in 11 (21%). The remaining patient (2%) showed mild dysplasia with koilocytosis. These 12 patients underwent colpostopically directed biopsies. Koilocytosis alone was confirmed by biopsy in 11 of 12 patients (92%). One patient (8%) had CIN I noted on biopsy. All patients were then treated with cryotherapy. DISCUSSION A review of the literature reveals a variety of recommendations for follow-up and management of atypical or mildly dysplastic Pap smears. The “treat and repeat” system of Nyitjesy [I] followed here has considerable support in the literature. Hulka reported that if a smear reverted to normal from Class II, the probability that subsequent smears would be negative was high (80-92%) [2]. In addition, she showed that the longer the interval of time allowed for healing from the presumed inflammatory insult, the larger the percentage of regression to normal. Hall and Walton’s work would support this conservative approach [lo]. In dysplasia regressed in 62.2% of patients with no therapy their study, “slight” (except for biopsies performed). The abnormality persisted in 24.4% and progressed in only 13.4%. Buckley et al. [ll] and Meisels [I21 agreed that mild dysplasia may be confused with inflammatory changes and recommend a treat and repeat plan of follow-up. Their recommendations are based upon the fact that the most severe histological lesion can be predicted in about 80% of cases from this cytological smear [I31 and that, in their experience, false-negative smears are rare [12,14]. Other authors disagree. Koss noted that Nyijesy showed carcinoma in situ in one-quarter of his patients with persistent atypia [3]. Figge and associates concurred [14]. Koss further maintained that repeat smears are negative in 30-
152
BROWN
AND
PHILLIPS
40% of patients with CIS. Rubio found a similar figure in an independent investigation [15]. Rylander showed similar findings in a study of invasive cervical cancer [16]. Twenty-three patients had follow-up initiated by cytology. Evaluation was discontinued, though, when follow-up cytology was negative. All were later diagnosed as invasive cervical cancer. For these reasons, Koss and others believe that a repeat smear after a Class II Pap smear is unreliable. Instead, they feel that colposcopy is mandatory [ 17,181. The present study following the recommendations of Nyirjesy showed regression rates of 58% for patients with mild dysplasia and 80.1% for patients with inflammatory atypia. These findings support the efficacy of the treat and repeat approach. Considering the large number of Pap smears performed in many centers and the considerable cost of colposcopy and biopsy, the follow-up procedure of Nyirjesy seems a rational approach. In addition, patient discomfort and anxiety would be minimized. Colposcopically directed biopsies on patients with persistently abnormal smears, however, showed CIN III in 30% of patients. Patients with persistently abnormal smears or in whom follow-up is questionable, should be promptly evaluated with colposcopy. However, in no case was an invasive carcinoma of the cervix missed by this conservative approach. Recommendations concerning follow-up and therapy of HPV infections of the cervix (as suggested by Pap smear) are unclear. Pap smears will show koilocytosis in l-2% of cases [4,7] and 70% of mild dysplasia can be reclassified as koilocytosis on reexamination [7]. HPV infections may coexist with dysplastic and neoplastic lesions in 25.6 to 91% of cases [7,81. Such findings have led to recommendations that HPV infections be evaluated and treated as are conventional forms of CIN
[51. In the present study, 76.4% of patients with Pap smears consistent with HPV infection regressed to negative without intervening therapy. Meisels had previously reported a 68.39% regression rate [7]. Whether this reflects regression of HPV infection or the incorporation of the viral genome into the cervical epithelium is unknown. These figures do, however, support a conservative approach of continued cytological evaluation for patients with findings suggestive of HPV on a single Pap smear. Because prospective studies are lacking and the absence of HPV cannot be guaranteed, patients with normal repeat smears should continue close follow-up. Patients with persistence or progression of findings suggestive of HPV infection or patients in whom follow-up cannot be guaranteed, should have further evaluation with colposcopically directed biopsies to rule out coexistent CIN. Though 92% of the patients who underwent colposcopically directed biopsies in the present study were noted to have koilocytosis only on histologic diagnosis, a strong, possibly etiologic, association of HPV with CIN warrants further immediate evaluation for these patients. CONCLUSION
(1) For patients with no history of previous cervical pathology or treatment, an initial conservative approach to mildly abnormal Pap smears is justified. If atypia or mild dysplasia were noted on cytologic evaluation, regression to normal
ABNORMAL
PAP SMEAR MANAGEMENT
153
occurred in 80.1 and 58%, respectively, after administration of specific intravaginal medication. (2) For patients with persistently abnormal smears or for those patients in whom follow-up cannot be guaranteed, prompt referral for colposcopy is recommended, as 30% of such patients demonstrated CIN III on colposcopically directed biopsies in the present study. (3) In no case was invasive carcinoma of the cervix missed by the conservative approach taken. (4) For patients with a single Pap smear suggestive of HPV infection, an initial conservative approach may be taken, as 76.4% of patients showed no abnormality on follow-up smear. The patients with persistently abnormal smears should be evaluated by colpostopically directed biopsies and treated appropriately, though CIN I was the most severe histologic lesion noted in the present study. (5) Further long-term prospective studies concerning HPV infections are needed before final recommendations concerning management can be made. REFERENCES 1. Nyitjesy, I. Atypical or suspicious cervical smears: An aggressive diagnostic approach, JAMA 222, 691-693
(1972).
Hulka, B. S. Cytologic and histologic outcome following an atypical cervical smear, Amer. J. Obstet. Gynecol. 101, 190-199 (1968). 3. Koss, L. G. Dysplasia: A real concept or a misnomer? O&et. Gynecol. 51, 374-379 (1978). 4. Ludwig, M. E., Lowell, D. M., and Livolsi, V. A. Cervical condylomatous atypia and its relationship to cervical neoplasia, Amer. J. Clin. Pathol. 76, 255-262 (1981). 5. Kaufman, R., Koss, L. G., Kurman, R. J., et al. Statement of caution in the interpretation of papillomavirus-associated lesions of the epithelium of the uterine cervix, Amer. J. Obstet. 2.
Gynecol.
146, 125.
6. Boon, M. E., and Fox, C. H. Simultaneous condyloma acuminatum and dysplasia of the uterine cervix, Acta Cytol. 25, 393-399 (1981). 7. Meisels, A., and Morin, C. Human papillomavirus and cancer of the uterine cervix, Gynecol. Oncol. 12, Slll-S123 (1981). 8. Reid, R., Stanhope, C. R., Herschman, B. R., et al. Genital warts and cervical cancer. I. Evidence of an association between subclinical papillomavirus infection and cervical malignancy, Cancer 50, 377-387 (1982). 9. Syjanen, K. L. Current concepts of human papillomavirus infections in the genital tract and their relationship to intraepithelial neoplasia and squamous cell carcinoma, Obstet. Gynecol. Surv.
39, 252-265
(1984).
10. Hall, J. E., and Walton, L. Dysplasia of the cervix: A prospective study of 206 cases, Amer. .I. Obstet.
Gynecol.
100, 662-668
(1968).
11. Buckley, C. H., Butler, E. B., and Fox, H. Cervical intraepithelial 35, l-13
neoplasia, J. C/in. Pathol.
(1982).
12. Meisels, A. Dysplasia and carcinoma of the uterine cervix. IV. A correlated cytologic and histologic study with special emphasis on vaginal microbiology, Acta Cyrol. 13, 224-231 (1969). 13. Husain, 0. A. N., Butler, E. B., Evans, D. M. D., ef al. Quality control in cervical cytology, J. Clin.
Pathol.
27, 935-944
(1974).
14. Figge, D. C., Bennington, J. L., and Schweid, A. I. Cervical cancer after initial negative and atypical vaginal cytology, Amer. J. Obstet. Gynecol. 108, 422-428 (1970). 15. Rubio, C. A. The false negative smear (letter to the editor), Amer. J. Obstet. Gynecol. 119, 273 (1974).
16. Rylander, E. Cervical cancer in women belonging to a cytologically screened population, Acta Obstet.
Gynecol.
Stand.
55, 361-366
(1976).
Feldman, M. J., Linzey, E. M., Srebnik, E., et al. Abnormal cervical cytology in the teen-ager: A continuing problem, Amer. J. Obstet. Gynecol. 126, 418-421 (1976). 18. Koss, L. G., and Coleman, D. V. Epidermoid carcinoma of the uterine cervix and related precancerous lesions, in Advances in clinical cytology, Butterworths, London, pp. 285-393 (1981). 17.