European Journul of‘ Obstetrics & Gynecolom 8
1992 Elsevier
EUROBS
Science
Publishers
and Reproductit,e Biology, 46 ( 1992) I43- 146
B.V. All rights
reserved
002%2243/92/$05.00
01397
Carbon dioxide laser treatment of cervical dysplasia in teenagers P. Sagot, Depurtmmt
of @necolo&y,
P. Lopes,
A. Mensier,
Obstetrics and Reproduction
Accepted
P. Barr&e
and G. Boog
Bioloml. Nanrex Unil,er.sity Hospital, Nunies, Frrrnce
for publication
9 June 1992
Summary Over a 6-year period, 40 young women under 20 years of age with cervical intraepithelial neoplasia (GIN) grade I (58%) to grade III (10%) were treated by laser vaporisation or excisional conisation. This prevalence of CIN in young women (nearly 4% of laser-treated cases> underscores the need for detection of cervical abnormalities in all teenagers engaged in sexual relations. The colposcopically-guided carbon dioxide laser technique is the treatment of choice for vaporisation and conisation of intraepithelial lesions (extending to the periphery of the cervix in 20% of cases) and for vaporisation of associated condylomatous lesions of the cervix (75%), vagina (23%), vulva (48%) and/or anus (8%). Teenager;
Carhon
dioxide
laser: Cervical
intraepithelial
neoplasia
Introduction A meeting to define the modalities for detection of invasive cervical cancers held during the last international French language gynecologists and obstetricians congress in Lille in September 1990 recommended a triennial cytological checkup for all women 25 to 65 years of age [5]. The extension of routine checkups for detection of preinvasive cervical lesions to most women, particularly older ones, should lead to a considerable reduction in the incidence of invasive cancers [6,8]. This procedure should not involve additional cost if cervical smears, currently per-
to: Dr. Paul Sagot, DCpartement de Gyntcologie-obstktrique et Biologie de la reproduction. H6pital Mkre-Enfant, C.H.R.U. de Nantes, B.P. 1005, 44035 Nantes Cedex 01, France. Correspondence
formed annually for 5 million French women (only), are also done on a triennial basis. However, the present study suggests that, if no regular cytological checkups are performed from the time of initial sexual relations to age 25, an appreciable number of teenagers will run the risk of late diagnosis of condylomatous infection and cervical dysplasia.
Patients
and Methods
Forty young women under 20 years of age underwent carbon dioxide laser treatment in our department for cervical intraepithelial neoplasia (GIN) between January 1985 and December 1990. Pretherapeutic examination, allowing anatomical mapping of lesions 1141, included colposcopy of the low genital tract and the perineum to detect condylomatous and dysplastic lesions, an endocervical smear and 6 to 12 microbiopsies
144
around the junction and cervical iodine-negative areas. Lesions were graded CIN I, II or III according to the Bethesda classification. The diagnosis of infection by human papilloma virus (HPV) was cytological (koilocytes); detection by molecular biology was only performed since 1989. Carbon dioxide laser treatment (initially by a Biophy-Las 80 and then by a Zeiss OPMI CO,-L) was performed under colposcopy (initially a Pzo. Op. M. and then a Zeiss OPMI) by vaporisation or conisation. With both techniques, the laser beam was guided by a micromanipulator fitted to the colposcope. General anaesthesia was routinely performed as well as vasoconstrictor infiltration (POR 8). Follow-up was only cytological until 1988 but has since included colposcopic examination, endoand ectocervical smears and in some cases guided microbiopsies 3 months after the procedure. Thereafter, biennial smears were performed if no abnormalities were detected. The results were analysed by the chi-square test, with possible modifications according to Yates (differences being considered significant when PI 0.05). Results
Although cervical dysplasia is considered a rare pathology in teenagers, we have handled around 10 cases in each of the last 3 years, representing 4% of the 704 CIN (284 I, 235 II, 185 III) treated by the carbon dioxide laser technique between January 1988 and December 1990. The mean age of these teenagers was 18.6 k 1.3 years, and 37 were nulliparous. The age of their first sexual relations, their smoking habits, their use of contraceptives and even their chlamydia and HIV serologies are unfortunately not known in all cases. Colposcopy always visualized the squamocolumnar junction at the level of the external cervical orifice. The iodine-negative zone was extensive in 20% of cases (involving two-thirds of the ectocervix in 6 patients and reaching the fornices of the vagina in 2 others). Condylomatous infection was observed in the cervix (30
cases, 75%), vagina (9 cases, 23%), vulva (19 cases, 48%) and/or anus (3 cases, 8%). Histopathological study of cervical biopsy specimens showed CIN I lesions in 23 patients (58%), CIN II in 13 (33%) and CIN III in 4 (10%). No correlation was found between the severity of histopathological grade and patient age, parity, colposcopic data or viral involvement. Dysplastic lesions were destroyed by laser vaporisation in 92.5% of cases (23 CIN I, 12 CIN II, 2 CIN III) and by laser conisation in 7.5% (1 CIN II, 2 CIN III). Condylomatous lesions of the genital tract were treated by laser vaporisation during the same procedure. There were no severe hemorrhagic complications requiring hemostatic suture or blood transfusion. Three patients (7.5%: 1 CIN I, 2 CIN II) could not be located and followed up. There were 6 failures, as defined by persistence of dysplastic lesions 3 months after surgery (made for CIN III in 2 cases, CIN II in 2 cases and CIN I in 2 others). These were always grade I lesions associated with koilocytes. Two healed spontaneously within 6 and 9 months, and one worsened to grade III in less than 6 months. A second treatment performed in 4 cases (10%) involved vaporisation 3 times and repeated conisation one time. The mean follow-up period was 14.4 & 12 months. A single patient, cured by a second vaporisation procedure, had dysplastic and condylomatous recurrence 3 years after her initial treatment, with CIN I progressing to grade III within less than 6 months. No patient presented subsequent invasive lesions. Discussion
Abnormal smears in teenagers have a certain prevalence: 6.6% according to Zaninetti et al. [163 and 7% according to Benmoura et al. [3] who differentiated viral involvement (5.9%) from dysplasia (1.1% as compared to 1.9% for Sadeghi et al. [131X CIN III have been found in 0% [3], 2% [16], 5% [13] and 10% (our study) of teenagers with dysplastic lesions in cervical biopsy specimens.
14.5
Although it has been estimated that 30 to 40% of dysplastic lesions disappear spontaneously [ 11,121, it would still seem essential to treat young women with high CIN grades or lesions that persist after 6 months of follow-up. There is a risk of rapid worsening of dysplasia (as noted in our study in 2 nonimmunosuppressed patients) as a result of cervical infection by the most oncogenie HPV (serotypes 16, 18 and 33), heavy smoking and/or a high number of sex partners [4,7,161. Moreover. teenagers are not as easy as their elders to follow up regularly or on a long-term basis, and they contribute quite considerably to the dissemination of genital condylomatosis. The carbon dioxide laser is entirely suitable for treatment of teenagers, proving just as oncologically reliable (90% cure after a single treatment and 100% after two treatments) as in older patients [1.5]. Laser beam impact is precise both in width and depth, and continuous guided colposcopy is possible during vaporisation, conisation and associations of both techniques [2]. The laser can totally destroy cervical dysplastic lesions, which in some cases extend to the fornices of the vagina (5% of our patients), as well as all viral lesions of the genital tract (75% for the cervix, 23% for the vagina, 48% for the vulva and 8% for the anus in our series). Destruction of lesions by vaporisation was achieved quite often in these very young women whose squamocolumnar junction was always totally examinable by colposcopy in our series. The destruction should include the first 5 to 10 mm of normal tissue in order to eradicate the HPV asymptomatically present in basement membrane around lesions [IO]. However, conisation or associated conisation and vaporisation should be performed when there is risk of microinvasion of the underlying chorion, i.e., when anatomical mapping locates extensive or multifocal epitheliomatous lesions in situ [l]. The surgical specimen is then perfectly analysable [14]. It is preferable to perform these treatments under general anaesthesia or neuroanalgesia because of the small size of the vagina in these nulliparae and the frequent spreading of viral lesions. The hemostatic properties of the carbon dioxide laser make sutures unnecessary, thus conserv-
ing cervical morphology and preserving the fertility of these young women while allowing easier and more reliable endo- and ectocervical oncological follow-up. Hemorrhagic complications are quite infrequent and healing is rapid. The repetition by the surgeon himself of endoand ectocervical smears, colposcopy and possibly guided microbiopsies 3 months after the procedure is performed greatly minimizes the risk of therapeutic failures since these 3 diagnostic approaches have a very low false-negative rate (1 .S% according to Falcone and Ferenczy [9]) and few patients drop out during this period. When there are no abnormalities, subsequent follow-up can be limited to simple biennial smears. Conclusion If triennial cytological checkups have been recommended for 25 to 65-year-old patients [5], these data show that it is also essential to keep watch over young women under 25 years of age who have had sexual relations. For conservative treatments, the carbon dioxide laser performed under colposcopy would seem preferable to other techniques [ 151. References 1 Abdul-Karim FW, Nunez C. Cervical intraepithelial neoplasia after conization. Obstet Gynecol 1985;65:77-81. 2 Baggish MS. Carbon dioxide laser for combination excisional-vaporization for the treatment of cervical intraepithelial neoplasia. Am J Obstet Gynecol 3985;151:23-27. 3 Benmoura D, Sperandeo D, Duprez D. DCpistage cervical et surveillance du co1 avant vingt ans. J Gynecol Obstet Biol Reprod 1986;35:63-71. 4 Bremond A. Facteurs de risque du cancer du co1 de I’uterus. J Gynecol Obstet Biol Reprod 1990;19:9-10. 5 Conference de consensus sur le depistage du cancer du col uterin. XXXJIIeme congrks de la federation des gyoecologues et obstetriciens de langue franfaise. Lille, S-8 September 1990. J Gynecol Obstet Biol Reprod 1990;19: 7-16. 6 Crepin G, Leroy-Brasme T. Qui doit depister? J Gynecol Obstet Biol Reprod 1990;19: 13. 7 Cuzick J, Singer A. De Stavola BL, Chomet J. Case-control study of risk factors for cervical intraepitheliai neoplasia in young women. Eur J Cancer 26:684-690. 8 Day NE. Age et frequence du dtpistage du cancer du co]. J Gynecol Obstet Biol Reprod 1990;lY:12-13.
146 9 Falcone T, Ferenczy A. Cervical intraepithelial neoplasia and condyloma. An analysis of diagnostic accuracy of post-treatment follow-up methods. Am J Obstet Gynecol 1986;154:260-264. 10 Ferenczy A, Mitao M, Nagai N, Silverstein SJ, Crum CP. Latent papillomavirus and recurring genital warts. N Engl J Med 1985;313:784-788. 11 Macgregor JE. Uterine cervical cytology and young women. Lancet 1978;i:1029-1031. 12 Richart RM. Causes and management of cervical intraepithelial neoplasia. Cancer 1987;60:1951-1959. 13 Sadeghi SB. Hsieh EW, Gunn SW. Prevalence of cervical intraepithelial neoplasia in sexually active teenagers and young adults. Am J Obstet Gynecol 1984;726-729.
14 Sagot P, Lopes P, Audoin AF, Dantal F, Anger P, Lerat MF. Traitements conservateurs des CIN III. J Gynecol Obstet Biol Reprod 1988;17:661-674. 15 Sagot P, Lopes P, Antonielli D, Barr&e P, Dantal F, Lerat MF. Cervical intraepithelial neoplasia III treatments by carbon dioxide laser. Eur J Obstet Gynecol Reprod Biol 1990;37:183-189. 16 Zaninetti P, Franceschi S, Baccolo M, Bonazzi B, Gottardi G, Serraino D. Characteristics of women under 20 with cervical intraepithelial neoplasia. Int J Epidemiol 1986; 15:477-482.
1992 Elsevier
EUROBS
Science
Publishers
and Reproductit,e Biology, 46 ( 1992) I43- 146
B.V. All rights
reserved
002%2243/92/$05.00
01397
Carbon dioxide laser treatment of cervical dysplasia in teenagers P. Sagot, Depurtmmt
of @necolo&y,
P. Lopes,
A. Mensier,
Obstetrics and Reproduction
Accepted
P. Barr&e
and G. Boog
Bioloml. Nanrex Unil,er.sity Hospital, Nunies, Frrrnce
for publication
9 June 1992
Summary Over a 6-year period, 40 young women under 20 years of age with cervical intraepithelial neoplasia (GIN) grade I (58%) to grade III (10%) were treated by laser vaporisation or excisional conisation. This prevalence of CIN in young women (nearly 4% of laser-treated cases> underscores the need for detection of cervical abnormalities in all teenagers engaged in sexual relations. The colposcopically-guided carbon dioxide laser technique is the treatment of choice for vaporisation and conisation of intraepithelial lesions (extending to the periphery of the cervix in 20% of cases) and for vaporisation of associated condylomatous lesions of the cervix (75%), vagina (23%), vulva (48%) and/or anus (8%). Teenager;
Carhon
dioxide
laser: Cervical
intraepithelial
neoplasia
Introduction A meeting to define the modalities for detection of invasive cervical cancers held during the last international French language gynecologists and obstetricians congress in Lille in September 1990 recommended a triennial cytological checkup for all women 25 to 65 years of age [5]. The extension of routine checkups for detection of preinvasive cervical lesions to most women, particularly older ones, should lead to a considerable reduction in the incidence of invasive cancers [6,8]. This procedure should not involve additional cost if cervical smears, currently per-
to: Dr. Paul Sagot, DCpartement de Gyntcologie-obstktrique et Biologie de la reproduction. H6pital Mkre-Enfant, C.H.R.U. de Nantes, B.P. 1005, 44035 Nantes Cedex 01, France. Correspondence
formed annually for 5 million French women (only), are also done on a triennial basis. However, the present study suggests that, if no regular cytological checkups are performed from the time of initial sexual relations to age 25, an appreciable number of teenagers will run the risk of late diagnosis of condylomatous infection and cervical dysplasia.
Patients
and Methods
Forty young women under 20 years of age underwent carbon dioxide laser treatment in our department for cervical intraepithelial neoplasia (GIN) between January 1985 and December 1990. Pretherapeutic examination, allowing anatomical mapping of lesions 1141, included colposcopy of the low genital tract and the perineum to detect condylomatous and dysplastic lesions, an endocervical smear and 6 to 12 microbiopsies
144
around the junction and cervical iodine-negative areas. Lesions were graded CIN I, II or III according to the Bethesda classification. The diagnosis of infection by human papilloma virus (HPV) was cytological (koilocytes); detection by molecular biology was only performed since 1989. Carbon dioxide laser treatment (initially by a Biophy-Las 80 and then by a Zeiss OPMI CO,-L) was performed under colposcopy (initially a Pzo. Op. M. and then a Zeiss OPMI) by vaporisation or conisation. With both techniques, the laser beam was guided by a micromanipulator fitted to the colposcope. General anaesthesia was routinely performed as well as vasoconstrictor infiltration (POR 8). Follow-up was only cytological until 1988 but has since included colposcopic examination, endoand ectocervical smears and in some cases guided microbiopsies 3 months after the procedure. Thereafter, biennial smears were performed if no abnormalities were detected. The results were analysed by the chi-square test, with possible modifications according to Yates (differences being considered significant when PI 0.05). Results
Although cervical dysplasia is considered a rare pathology in teenagers, we have handled around 10 cases in each of the last 3 years, representing 4% of the 704 CIN (284 I, 235 II, 185 III) treated by the carbon dioxide laser technique between January 1988 and December 1990. The mean age of these teenagers was 18.6 k 1.3 years, and 37 were nulliparous. The age of their first sexual relations, their smoking habits, their use of contraceptives and even their chlamydia and HIV serologies are unfortunately not known in all cases. Colposcopy always visualized the squamocolumnar junction at the level of the external cervical orifice. The iodine-negative zone was extensive in 20% of cases (involving two-thirds of the ectocervix in 6 patients and reaching the fornices of the vagina in 2 others). Condylomatous infection was observed in the cervix (30
cases, 75%), vagina (9 cases, 23%), vulva (19 cases, 48%) and/or anus (3 cases, 8%). Histopathological study of cervical biopsy specimens showed CIN I lesions in 23 patients (58%), CIN II in 13 (33%) and CIN III in 4 (10%). No correlation was found between the severity of histopathological grade and patient age, parity, colposcopic data or viral involvement. Dysplastic lesions were destroyed by laser vaporisation in 92.5% of cases (23 CIN I, 12 CIN II, 2 CIN III) and by laser conisation in 7.5% (1 CIN II, 2 CIN III). Condylomatous lesions of the genital tract were treated by laser vaporisation during the same procedure. There were no severe hemorrhagic complications requiring hemostatic suture or blood transfusion. Three patients (7.5%: 1 CIN I, 2 CIN II) could not be located and followed up. There were 6 failures, as defined by persistence of dysplastic lesions 3 months after surgery (made for CIN III in 2 cases, CIN II in 2 cases and CIN I in 2 others). These were always grade I lesions associated with koilocytes. Two healed spontaneously within 6 and 9 months, and one worsened to grade III in less than 6 months. A second treatment performed in 4 cases (10%) involved vaporisation 3 times and repeated conisation one time. The mean follow-up period was 14.4 & 12 months. A single patient, cured by a second vaporisation procedure, had dysplastic and condylomatous recurrence 3 years after her initial treatment, with CIN I progressing to grade III within less than 6 months. No patient presented subsequent invasive lesions. Discussion
Abnormal smears in teenagers have a certain prevalence: 6.6% according to Zaninetti et al. [163 and 7% according to Benmoura et al. [3] who differentiated viral involvement (5.9%) from dysplasia (1.1% as compared to 1.9% for Sadeghi et al. [131X CIN III have been found in 0% [3], 2% [16], 5% [13] and 10% (our study) of teenagers with dysplastic lesions in cervical biopsy specimens.
14.5
Although it has been estimated that 30 to 40% of dysplastic lesions disappear spontaneously [ 11,121, it would still seem essential to treat young women with high CIN grades or lesions that persist after 6 months of follow-up. There is a risk of rapid worsening of dysplasia (as noted in our study in 2 nonimmunosuppressed patients) as a result of cervical infection by the most oncogenie HPV (serotypes 16, 18 and 33), heavy smoking and/or a high number of sex partners [4,7,161. Moreover. teenagers are not as easy as their elders to follow up regularly or on a long-term basis, and they contribute quite considerably to the dissemination of genital condylomatosis. The carbon dioxide laser is entirely suitable for treatment of teenagers, proving just as oncologically reliable (90% cure after a single treatment and 100% after two treatments) as in older patients [1.5]. Laser beam impact is precise both in width and depth, and continuous guided colposcopy is possible during vaporisation, conisation and associations of both techniques [2]. The laser can totally destroy cervical dysplastic lesions, which in some cases extend to the fornices of the vagina (5% of our patients), as well as all viral lesions of the genital tract (75% for the cervix, 23% for the vagina, 48% for the vulva and 8% for the anus in our series). Destruction of lesions by vaporisation was achieved quite often in these very young women whose squamocolumnar junction was always totally examinable by colposcopy in our series. The destruction should include the first 5 to 10 mm of normal tissue in order to eradicate the HPV asymptomatically present in basement membrane around lesions [IO]. However, conisation or associated conisation and vaporisation should be performed when there is risk of microinvasion of the underlying chorion, i.e., when anatomical mapping locates extensive or multifocal epitheliomatous lesions in situ [l]. The surgical specimen is then perfectly analysable [14]. It is preferable to perform these treatments under general anaesthesia or neuroanalgesia because of the small size of the vagina in these nulliparae and the frequent spreading of viral lesions. The hemostatic properties of the carbon dioxide laser make sutures unnecessary, thus conserv-
ing cervical morphology and preserving the fertility of these young women while allowing easier and more reliable endo- and ectocervical oncological follow-up. Hemorrhagic complications are quite infrequent and healing is rapid. The repetition by the surgeon himself of endoand ectocervical smears, colposcopy and possibly guided microbiopsies 3 months after the procedure is performed greatly minimizes the risk of therapeutic failures since these 3 diagnostic approaches have a very low false-negative rate (1 .S% according to Falcone and Ferenczy [9]) and few patients drop out during this period. When there are no abnormalities, subsequent follow-up can be limited to simple biennial smears. Conclusion If triennial cytological checkups have been recommended for 25 to 65-year-old patients [5], these data show that it is also essential to keep watch over young women under 25 years of age who have had sexual relations. For conservative treatments, the carbon dioxide laser performed under colposcopy would seem preferable to other techniques [ 151. References 1 Abdul-Karim FW, Nunez C. Cervical intraepithelial neoplasia after conization. Obstet Gynecol 1985;65:77-81. 2 Baggish MS. Carbon dioxide laser for combination excisional-vaporization for the treatment of cervical intraepithelial neoplasia. Am J Obstet Gynecol 3985;151:23-27. 3 Benmoura D, Sperandeo D, Duprez D. DCpistage cervical et surveillance du co1 avant vingt ans. J Gynecol Obstet Biol Reprod 1986;35:63-71. 4 Bremond A. Facteurs de risque du cancer du co1 de I’uterus. J Gynecol Obstet Biol Reprod 1990;19:9-10. 5 Conference de consensus sur le depistage du cancer du col uterin. XXXJIIeme congrks de la federation des gyoecologues et obstetriciens de langue franfaise. Lille, S-8 September 1990. J Gynecol Obstet Biol Reprod 1990;19: 7-16. 6 Crepin G, Leroy-Brasme T. Qui doit depister? J Gynecol Obstet Biol Reprod 1990;19: 13. 7 Cuzick J, Singer A. De Stavola BL, Chomet J. Case-control study of risk factors for cervical intraepitheliai neoplasia in young women. Eur J Cancer 26:684-690. 8 Day NE. Age et frequence du dtpistage du cancer du co]. J Gynecol Obstet Biol Reprod 1990;lY:12-13.
146 9 Falcone T, Ferenczy A. Cervical intraepithelial neoplasia and condyloma. An analysis of diagnostic accuracy of post-treatment follow-up methods. Am J Obstet Gynecol 1986;154:260-264. 10 Ferenczy A, Mitao M, Nagai N, Silverstein SJ, Crum CP. Latent papillomavirus and recurring genital warts. N Engl J Med 1985;313:784-788. 11 Macgregor JE. Uterine cervical cytology and young women. Lancet 1978;i:1029-1031. 12 Richart RM. Causes and management of cervical intraepithelial neoplasia. Cancer 1987;60:1951-1959. 13 Sadeghi SB. Hsieh EW, Gunn SW. Prevalence of cervical intraepithelial neoplasia in sexually active teenagers and young adults. Am J Obstet Gynecol 1984;726-729.
14 Sagot P, Lopes P, Audoin AF, Dantal F, Anger P, Lerat MF. Traitements conservateurs des CIN III. J Gynecol Obstet Biol Reprod 1988;17:661-674. 15 Sagot P, Lopes P, Antonielli D, Barr&e P, Dantal F, Lerat MF. Cervical intraepithelial neoplasia III treatments by carbon dioxide laser. Eur J Obstet Gynecol Reprod Biol 1990;37:183-189. 16 Zaninetti P, Franceschi S, Baccolo M, Bonazzi B, Gottardi G, Serraino D. Characteristics of women under 20 with cervical intraepithelial neoplasia. Int J Epidemiol 1986; 15:477-482.
