Cervical intraepithelial neoplasia III treatments by carbon dioxide laser

European Journal of Obstetrzcs & Gynecology and Reproductive Elsevier

EUROBS

Biology, 31 (1990) 183-189

183

00981

Cervical intraepithelial neoplasia III treatments by carbon dioxide laser P. Sagot r, P. Lopes *, D. Antonielli 2, P. Barr&e and M.F. Lerat ’

r, F. Dantal

’

’ Department of Gynecology, Obstetrics and Reproductzon Biolagy, and 2 Data Processzng and Medzcal Statzstics Unit, Nantes, France Accepted

for publication

9 November

1989

162 women underwent one or more carbon dioxide laser conservative treatments for lesions of severe dysplasia and cervical intraepithelial neoplasia (CIN III) between 1982 and 1987. Therapy involved destruction of lesions by vaporisation in 45% of cases and excisional conisation in 55% (32% performed with a hand-held apparatus and 23% colposcopically guided). Rates of cure were, respectively, 93, 96.1 and 94.4% with an overall rate of 2.5% for dropouts. Recurrences (rates, respectively, of 8.5, 5.8 and 5.5%) were associated with human papilloma virus in 92% of cases. The increasing numbers of very young women affected, as well as the spread of intraepithelial and condylomatous neoplastic lesions along the endocervical canal, are major reasons for the use of colposcopically guided carbon dioxide laser treatment. Laser surgery;

Cervtcal

intraepithelial

neoplasla

Introduction The increasing number of very young women with low parity presenting with cervical intraepithelial neoplasia has led to the development of conservative treatments to provide reliable oncological results. The frequency of the spread of neoplastic and/or condylomatous lesions to the periphery of the ectocervix and/or the fornix vaginae prompted our choice of colposcopically guided carbon dioxide laser treatments. The present study compares the results of three therapeutic carbon

Correspondence: Dr. Paul Sagot, Dtpartement Pavillon Mbre et Enfant, C.H.R. de Nantes,

0028-2243/90/$03.50

de Gynkologie-obstttrique B.P. 1005, 44035 Nantes

0 1990 Elsevier Science Publishers

et Biologie de la reproduction, Cedex, France.

B.V. (Biomedical

Diwsion)

184

dioxide laser techniques for treatment of grade III cervical intraepithelial neoplasia and considers their respective indications and the conditions of early detection, therapeutic failure and recurrence. Patients and Methods

162 women received a total of 174 carbon dioxide laser conservative treatments for grade III cervical intraepithelial neoplasia (CIN III) between January 1982 and December 1987. The diagnosis of CIN III was based on histopathology. A distinction was made between severe dysplasia and intraepithelial epithelioma, and the presence of koilocytes was considered to be pathognomonic of infection by human papilloma virus (HPV). Comparison of the results of endo- and ectocervical smears, colposcopy and 6 to 12 microbiopsies, performed on suspect lesions and at the squamocolumnar junction, enabled the cervical region to be charted for therapeutic application. Destruction of all lesions by laser vaporisation was contraindicated when the three diagnostic methods failed to confirm the absence of involvement of the underlying chorion (discordance in findings, impossibility of examining the entire squamocolumnar junction or very extensive foci of intraepithelial epithelioma) and when postoperative follow-up was uncertain. Colposcopically guided vaporisation was performed most often in outpatient conditions, with or without cervical vasoconstrictor infiltration (POR 8) and with preliminary antibiotic therapy. Eradication of lesions by laser conisation was done either with a hand-held apparatus or (since the end of 1986) under colposcopy according to the technique described by Baggish and Dorsey [4] and Wright et al. [14] without hemostatic sutures. The laser beam (Biophy Las. 80; power 900 to 1400 W/cm*) was guided, as for vaporisations, by a micromanipulator fitted to the colposcope (Pzo. Op. 1). The operator worked alone, positioning the cervix and then the cone with a Gillies’ hook. General anaesthesia was routine as was vasoconstrictor infiltration. Clinical and cytologic follow-up was carried out 3, 6, 12 and 18 months after treatment and then annually. Repetition of the three pretherapeutic acts (smears, colposcopy and microbiopsies) 3 months after treatment was only done systematically from the beginning of 1987. Therapeutic failure was defined as the persistence of neoplastic lesions 3 months after treatment. The results were collected and analyzed every year (most recently in October 1988). The &i-square test and Student’s f-test were used for analysis. Results

The initial treatment performed for these 162 women was destruction of all lesions by vaporisation in 45% of cases (73 women; 28.5 f 4.7 years *; parity 0.8 children) and their excision by conisation using the hand-held apparatus in 32% of

* Statistically

significant

difference.

185 TABLE

I Vaporisation

Conisation Hand-held

Women Age Dropouts Cures 1 st Treatment Laser Alone

73 28.5 2.7%

51 33 0%

App.

colposcopy 38 31.4 5.3%

83.1% 93%

94.1% 96.1%

83.3% 94.4%

Recurrences

8.5%

6.1%

5.5%

Hysterectomies

0%

7.8%

5.4%

cases (51 women; 33 * 6.8 years *; parity 1.2 children) or under colposcopic guidance in 23% (38 women; 31.4 I~I7.8 years *; parity 1.3 children) (Table I). In 19% of cases, colposcopy did not allow the entire squamocolumnar junction to be examined. The mean age of women presenting an endocervical junction (visualized or not) was statistically higher than that of women presenting an ectocervical or external OS junction (33.5 _+ 7.3 vs. 29.2 + 5.1 years; Student t-test = 4.36). The iodine-negative zone was very extensive (greater than 75% of the ectocervix), reaching or not one or more fornices of the vagina in 9.3% of women. A viral infection of the cervix and/or vulva affected, respectively, 70 and 12.3% of these women. Three types of cervical topography could be distinguished: (1) presence of a limited focus of severe dysplasia or intraepithelial epithelioma within lesions of lesser severity (56.7%); (2) bifocal CIN III lesions (9.9%); and (3) presence of very extensive intraepithelial epithelioma (33.3%). Vaporisation was used to treat 62% of the first type, whereas 85% of the third type were treated by one of the two laser conisation techniques. The percentages of women cured by these treatments were 93% after vaporisation and 96.1 and 94.4%, respectively, after conisation performed with the hand-held apparatus or colposcopically guided. The percentages of women not reexamined since their treatment were, respectively, 2.7, 0 and 5.3% (mean rate: 2.5%). Initial treatment sometimes had to be repeated or modified. The rates of cure after 1, 2 and 3 vaporisations were, respectively, 83.1, 90.1 and 93%. The residual lesion was grade III in only 50% of these failures. Five women (6.8%) were treated by a second vaporisation, and two women (2.7%) required three vaporisations; these seven women are presently cured. Three secondary conisations were performed with the carbon dioxide laser and a fourth with a cold knife (5.6%). In the latter case, the residual neoplasia was located on an endocervical polyp which was removed by curet. The rate of cure after a single conisation using the hand-held laser was 94.1%. A secondary vaporisation (2%) and two hysterectomies (3.9%) were performed for residual CIN II lesions found in surgical specimens. Two hysterectomies (3.9%) were

186

performed because of suspected section of a dysplastic zone, and two others systematically. None of these four surgical specimens presented residual lesions. The rate of cure after laser use alone was 96.1%. The rate of cure after a single laser conisation performed according to the technique of Baggish was 83.3%. Three secondary vaporisations (8.3%) and a laser conisation (2.8%), also colposcopically guided, were required to treat six residual lesions (4 CIN III and 2 CIN I). One pregnant woman, presenting with residual CIN I, is currently being followed-up. Two hysterectomies (5.6%) were performed for CIN III lesions which were residual in one case and recurrent in the other. The rate of cure after laser use alone was 94.4%. The rate of secondary hysterectomy was zero for women initially treated by vaporisation, and 7.8 and 5.4%, respectively, in women treated by conisation using a hand-held apparatus or colposcopically guided. The laser effect did not alter the histopathological diagnostic accuracy of conisation specimens, including one revealing underlying chorion involvement not detected by one of our infrequent preoperative macrobiopsies. The presence of neoplastic lesions in the endocervical section was noted for 5.9% of conisations done with the hand-held apparatus and for 7.9% of those colposcopically guided. This feature was predictive of residual lesions, which were found in two of the three hysterectomies performed for this reason after conisation using the hand-held apparatus, and in all three performed after colposcopically guided conisation. In two cases (one for each technique, 2.2%), residual lesions (CIN III and CIN II) were diagnosed 3 months after treatment, whereas the section was remote from any dysplastic or metaplastic focus. The mean follow-up periods were 22.1 + 12.7 months after vaporisations, 27.9 + 18.5 months after conisation with a hand-held apparatus and 12.1 f 5.2 months after colposcopically guided conisation. The rates of recurrence were, respectively, 8.5, 6.1 and 5.5% for mean follow-up periods of 17 f 6.5, 14 f 7.2 and 9 f 4.2 months. Cervical intraepithelial neoplasia was grade III in, respectively, 67.0 and 50% of cases, and associated with HPV in 92% of cases. These recurrences were treated by vaporisation (40%) and laser conisation (30%). One woman was treated by hysterectomy (10%) and two (20%) are currently being followed up, one of whom is pregnant and presenting CIN III. Worsening of neoplasia was very rapid in two women under 20 years of age who presented with a cervical HPV localisation (CIN I to CIN III within 4 and 5 months, respectively). No secondary involvement was diagnosed in this series. Overall, 15% of these women have had a pregnancy at term subsequent to treatment. Discussion Destruction or excision of noninvasive cervical neoplasia by laser action is a simple and rapid form of treatment which can be done in outpatient conditions and proves effective in terms of oncological results. The rates of cure after 1 and 2 vaporisations have been greater than 90 and 95% (reaching even 99%) in long series performed by a very limited number of operators [3,5,7,10,15]. These rates have

187

been the same after laser conisation performed with the hand-held apparatus [ll] or colposcopically guided [5,15]. The latter technique associates excision of a cervical cone (1.5 cm high and 0.6 mm thick), allowing histopathological study of the squamocolumnar junction and adjacent glands, with precise destruction of peripheral lesions of the cervix or vagina by vaporisation performed during the same operation. There are several reasons why conservative carbon dioxide laser therapy for CIN III should be considered preferable to radical treatments by total hysterectomy [13] and cold-knife conisation which require hemostatic sutures that can deform the cervix. First, young women (mean age: 31 years) with few children (mean: 1 child) generally wish to conserve their possibilities of procreation. Secondly, preserving the morphology of the cervix through the hemostatic effect of the carbon dioxide laser ensures more reliable oncological follow-up (smears, colposcopy, microbiopsies). Finally, and especially, the frequency of the spread of CIN and condylomatous lesions to the periphery of the cervix and/or to the fornix vaginae (9.3%) accounts for the not insignificant rates of failure of other techniques by ectocervical or vaginal section in a dysplastic or condylomatous zone. The therapeutic choice between vaporisation and laser conisation depends on the cervical situation, that is, on comparison of the data from endo- and ectocervical smears, colposcopy and 6 to 12 guided microbiopsies. Prevention of failure depends on the quality of the cervical topography and on respecting the rules of therapeutic procedure as outlined by Anderson (in Abdul-Karim et al. [l]) and Abdul-Karim and Nunez [2]. Destruction of lesions is contraindicated when the squamocolumnar junction cannot be totally examined, when the limits of the iodine-negative zone, the metaplastic zone and the viral lesions are not perfectly known; when biopsies show microinvasion of the chorion or high-risk of microinvasion (extensive lesions of the intraepithelial epithelioma; discordance among the three diagnostic methods); and when postoperative follow-up is uncertain. Vaporisation and conisation should be performed throughout the junction and metaplastic zones. All cervical tissue located less than 5 mm from the viral or dysplastic lesions or from the junction should be destroyed or removed. The publications of Baggish and Dorsey [4] and Wright et al. [14] on the use of the excisional-vaporisation laser technique under permanent colposcopic guidance changed our therapeutic approach for CIN III lesions [8,12]. Our rate of total destruction of lesions by laser vaporisation regressed from 51.8% for the period 1982-1986 to 27.9% for 1987. Since a surgical specimen cannot be obtained with the latter technique, our use of it is currently restricted to certain women presenting a very limited ectocervical focus of CIN III. Determination of therapeutic failures was based on two procedures. First, by histopathological study either of the cone or of smears or microbiopsies performed on the endocervix at the end of vaporisation. The presence of dysplastic lesions on or near the endocervical section of the cone, or in the smears or biopsies, is predictive of residual lesions, which were found by Abdul-Karim and Nunez [2] in 33 to 51% of cases, and even more frequently in our series. Their absence does not mean that residual lesions are inexistent, particularly in the case of an endocervical focus initially separated from the junction and from the main neoplastic focus

188

diagnosed [2,9]. Secondly, by repetition of the three diagnostic methods (ecto- and endocervical smears, colposcopy and guided microbiopsies) 3 months after laser treatment. Falcone and Ferenczy [6] have demonstrated that isolated performance of each of these examinations is subject to a high false-negative rate (respectively, 19, 8 and 5%), whereas their association during the same consultation 3 months after laser treatment lowers this rate enormously (1.5%) and permits continued follow-up by smears alone. This approach, which we have adopted, should limit the incidence and consequences of dropouts. Prevention of recurrences depends on several factors. A first consideration is the quality of colposcopic study at the time of pretherapeutic examination and during laser treatment. This affects the quality of treatment to be carried out on all dysplastic lesions and the metaplastic zone as well as on all viral lesions to be searched for along the entire endocervical canal, the urinary meatus and the perianal (indeed intra-anal) region. Secondly, an effort should be made to detect viral lesions in sexual partners by peniscopic examination. Finally, viral reinfestation should be prevented by use of condoms during at least 3 months following treatment. Diagnosis of recurrences should be based on uninterrupted repetition of ectoand endocervical smears every 3 months during the first year, then every 6 months and finally every year. Some dysplasias, particularly those associated with HPV serotypes 16, 18 or 33, are likely to worsen rapidly, as noted in our series for two adolescents who presented no known immunodeficiency factor. Conclusion

The carbon dioxide laser offers two types of conservative treatment of noninvasive cervical neoplasias: destruction of lesions by vaporisation and excisional conisation. These two techniques can be associated and performed under permanent colposcopic guidance for precise destruction of any dysplastic or peripheral viral lesion and to provide a surgical specimen containing the squamocolumnar junction and adjacent glands. They ensure preservation of cervical morphology as well as more reliable oncological follow-up. However, as for all types of conservative oncological treatment, their use implies respect for contraindications and the modalities of treatment and follow-up. References 1 Abdul-Karim FW, Fuys S, Reagan JW, Budd Wentz R. Morphometric study of intraepithelial neoplasia of the uterine cervix. Obstet Gynecol 1982;60:210-214. 2 Abdul-Karim FW, Nunez C. Cervical intraepithelial neoplasia after conization: a study of 522 consecutive cervical cones. Obstet Gynecol 185;65:77-81. 3 Ali SW, Evans AS, Monaghan JM. Results of carbon diaxide laser cylinder vaporisation of cervical intraepithelial disease in 1,234 patients. An analysis of failures. Br J Obstet Gynaecol 1986;93:75-78. 4 Baggish MS, Dorsey JH. Carbon dioxide laser for combination excisional-vaporization for the treatment of cervical intraepithelial neoplasia. Am J Obstet Gynecol 1985;151:23-27. 5 Baggish MS. A comparison between laser excisional conization and laser vaporization for the treatment of cervical intraepithelial neoplasia. Am J Obstet Gynecol 1986;155:39-44. 6 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.

189 7 Jordan JA, Woodman BJ, Mylotte MJ, Eman JM, Wilhams DR, Macalary M, Wade-Evans T. The treatment of cervical intraepithelial neoplasia by laser vaporisation. Br J Obstet Gynaecol 1985;92,394-398. 8 Lopes P, Sagot P. Petit-on proposer un traitement conservateur des dysplasies s&&es du co1 uterm? Dans quelles conditions7 Entrettens de Bichat Therapeutique. Besancon Fed. Paris: Expansion Scientifique Franqatse, 1988; 46-49. 9 Ostergard DR. Prediction of clearance of cervical mtraepithelial neoplasia. Am J Obstet Gynecol 1987;156:628-631. 10 Rylander E, Isberg A, Joelsson I Laser vaponsation of cervical mtraepithehal neoplasia. Acta Obstet Gynecol Stand Suppl 1984;125:33-36. 11 Sadoul GD. Beuret TM. Management of 633 cervical intraepithehal neoplasias by carbon dioxide laser: persistent diseases and recurrences. Lasers Surgery Medicine 1986;6: 110-118. 12 Sagot P, Lopes P, Audom AF, Dantal F, Anger P, Lerat MF. Traitements conservateurs des CIN III. Etude comparative des vaporisattons laser, des comsations laser et des conisations au btstoun frond. A propos de 141 cas. J Gynecol Obstet Biol Reprod 1988;17:661-674. 13 Van Nagell JR, Hanson MB, Donaldson ES, Gallion HH. Treatment of cervical intraeptthehal neoplasia III by hysterectomy without intervening conization in patients with adequate colposcopy. Cancer 1985;56:2737-2739. 14 Wnght VC, Davies E, Rtopelle MA, Laser surgery for cervical intraepithelial neoplasta: prmciples and results. Am J Obstet Gynecol 1983;145:181-184. 15 Wright VC. Laser surgery for cervical intraepnhelial neoplasia. Acta Obstet Gynecol Stand Suppl 1984:125:17-23.