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Opinions in Pediatric and Adolescent Gynecology
J Pediatr Adolesc Gynecol (1998) 11:97-99
Opinions in Pediatric and Adolescent Gynecology Edited by Sally Perlm泊 ， MD , Division of Gynecology , Department of Surgery , Children's Hospital and the Department of Obstetrics , Gynecology , and Reproductive Medicine , Brigham and Women's Hospital , Harvard Medical School , Boston , Massachusetts; and by Mary Anne Jamieson , MD , Ki ngston , Ontario ,.Canada
This Opinions section, once again , is written by a single author but is meant to be provocative. It represents a sun1mary of a topic presented at a recent NASPAG conference. This issue did not result in a consensus of opinion at the end of the workshop. The ideologies presented represent the differing treatment philosophy that exists today among our peers who treat the abnormal pap smear in the adolescen t.
Treatment of the High-Grade Squamous Intraepithelial Lesion of the Cervix in Adolescents: Loop Electrical Excision Procedure or Cryotherapy In a 1997 Committee Opinion from ACOG , it was recommended that high-grade squamous intraepithelial lesion (HSIL) of the cervix should be considered a genuine cancer precursor.! These lesions should be treated within a reasonable time. However , the urgency with which the treatment should be offered and which treatment should be offered are less established. The progressive potential of HSIL in adult women is clearly and indisputably established. Two recent studies show this. In one study , a group of 60 women had highgrade atypia on their smear but refused biopsy or 仕eat ment. 2 After a mean interval of 5 years , 19 women had reported negative follow-up cytology. This is only by subjective repor t. However , invasive cancer had developed in 13 women , representing a 22% progression rate within a reasonably short period of time. In addition , a group from New Zealand reported on 300 women who had cytological evidence of high-grade preinvasive disease that were left untreated over a 20-year period. 2 A total of 369毛developed cervical cancer. Clearly , the risk of invasive cervical cancer in the adolescent is very low. Earlier age at first intercourse does seem to have an associated significant risk for invasive cancer in adults when separating those into sex before age 20 and those before age 30.3 When comparing national data between the 1970s and the 198郎 ， those adolescents that were sexually active before the age of 19 had almost doubled. 4 In addition , some investigators have postulated that , in some women , there may be an 1083-3188 © 1998 Lippincott-Raven Publishers
increased transit time to cervical cancer. 5 When this information is put together , it is easy to understand that , although rates of cervical cancer have leveled off, the rates of carcinoma in situ (CIS) in young women aged 20-29 years in this country and in others have increased. 6 ,7 Hence , at this juncture , most clinicians would agree that treatment of HSIL in the adolescent is warranted. The treatment modalities have evolved over the years because knowledge and understanding of the disease process have increased. Most clinicians today would agree that HSIL can be treated using conservative office or outpatient ablative or excisional procedures. Cryosurgery and loop electrical excision procedure (LEEP) are the most common treatment modalities used to treat HSIL in this country today. Is one method superior for the treatment of the adolescent with HSIL? Cryosurgery Cryosurgery involves freezing of cervical tissue using nitrous oxide (preferable) or carbon dioxide delivered to the lesion through a multisized probe attached to a delivery system? ,8 As with all other conservative therapeutic modalities , destruction of the entire transformation zone including epithelium in the lower portion of the endocervical canal is necessary. The aim is to minimize the risk of residual atypia or future development of disease in the lower endocervical cana l. Failure to destroy the entire transformation zone with adequate depth is the most common cause of cryotherapy failure. Residual or recurrent disease often occurs in the lower endocervical canal , occasionally escaping detection and proceeding to invasive cancer. The frequently used flat cryosurgery probes may predispose to this recurrence. The lower endocervical canal must be adequately treated. The training for performing this ablative treatment is much easier to effect than the excisional procedures. Hence , the clinician needs to be familiar with all of the equipment and select the correct probe that will ablate the entire lesion. Adequate treatment will frequently result in the squamocolumnar junction being inaccessible to colposcopic view after treatmen t. This finding is common and simply mandates adequate endocervical sampling in future screenIng.
98
Opinions in PAG
The efficiency of cryosurgery in the treatment of premalignant disease of the cervix has been extensi vely studied. Cure rates range from 27%-96%? It is generally accepted that the primary cure rate of cryosurgery for premalignant cervical disease is about 85%. After second or third treatment , the cure rate is more than 95%. The most important factor determining treatment outcome is the size of the lesion. Failure may occur because highgrade lesions are frequently larger , involving two or more quadrants of the cervix. Treatment failure also tends to occur in patients with scarred cervices or with lesions close to the endocervical cana l. Cryosurgery has high patient acceptability , which is important in effecting adequate therapy for the adolescen t. The technique requires no anesthesia. Uterine cramping and vasovagal phenomena may occur during the procedure. Bleeding is uncommon. Overall , significant complications are uncommon. This is very important in the adolescent population in which consistent compliance may be problematic. One can discuss results and effect treatment at the same visi t. The procedure requires little equipment and produces little discomfort and few side effects , thus minimizing any negative connotations that may inhibit the adolescent from returning. Finally , for the adolescent , the long-term side effects of cryosurgery even after repetitive procedures are much less profound than one aggressive or several repeated excisional procedures such as the LEEP. Several clinicians cite the advantage of cervical stenosis after repeated cryotherapy over a severely foreshortened cervix after one aggressive LEEP. 5 Loop Electrical Excision Procedure Cryosurgery , although simple and inexpensive , is associated with significant persistence or recurrence of all grades of cervical dysplasia. 2 Abnormal cytology after cryosurgery is worrisome particularly because often the endocervix is constricted and the squamocolumnar junction is inaccessible , requiring a second , most likely excision祉 ， procedure. Residual or recurrent disease in the endocervical canal posttreatment carries the potential for misdiagnosis because , by the time of diagnosis , it may have advanced to invasive cance r. This is particularly worrisome if the number of young women with CIS is IncreasIng. Hence , because the nU1l1ber of young women requiring colposcopy for SIL has increased to almost epidemic proportions , the need for more effective diagnostic and therapeutic modalities has spawned the introduction of the large loop excision of the transformation zone (LLETZ). 8 The entire transformation zone is excised using thin wire-loop electrodes and an electrosurgical generato r. In the United States , in part to promote consideration of wider usage beyond the cervical transformation zone , the ter 1l1 loop electrosurgical excision procedure , or LEEP , has been coined. Loop electrosurgical excision of the transformation
zone in the treatment of premalignant cervical disease combines the advantages of conservative ablative techniques with the safety of histopathological analysis of the entire specimen. Cartier9 developed wire electrodes , the precursor to our present modes of this therapy. Prendiville et al IOmodified the electrodes by developing larger electrodes and in1proved electrosurgical generators. The larger loop electrodes allow for excision of the entire transformation zone and the area of disease frequently in one pass. If the lesion is large or irregular or extends into the endocervical canal , several passes may be required with differing size or shape loop electrodes to adequately excise the lesion. The range of loop sizes and shapes permits considerable flexibility in tailoring the excision to the topography and the lesion. Typically , the LEEP is performed as an office procedure under local anesthetic. The significant discomfort associated with the earlier electrosurgical generators does not occu r. The amount of thermal damage to the specimen after LEEP is comparable with an expert excision using a continuous-wave CO 2 laser; however, the equipment is vastly less expensive and much simpler to use. Several distinct , theoretical advantages of LEEP over ablative approaches exis t. First , unlike cryosurgery or laser ablation , the affected tissue is removed rather than destroyed. Second , unsuspected invasive cancer will not be ablated. Last , submission of the entire specimen for histological evaluation adds an extra safety dimension to diagnosis of occult invasive cancer. Results to date regarding the efficacy of the LEEP are encouraging. Wright and Richart 9 tallied the results of 4 ,578 loop excision procedures. The overall success rate is 93.5% , similar to that for laser ablation and slightly better than that for a single cryosurgery treatment. Bigrigg et alII performed a 2-year follow-up study and reported a 5% rate of recurrence or persistence at 1 year of follow-up and 0.6% in the second yea r. Complications include perioperative discomfort or bleeding in 2%-7% of procedures. 9 Postoperatively , one can see hemorrhage in about 1%--4%; infection, discharge complaints similar to those reported with cryosurgery. 9 Rates of cervical stenosis and unsatisfactory colposcopy vary with the depth of the excision but range between 1%_9%.9 Effects on fertility and pregnancy are Ie
99
Opinions in PAG operating room given the constraints of our institution. This has lead to some difficulty with compliance and long lengths of time-to-procedure because parental consent is required. Other institutions have been able to avoid these problems by performing their procedures in an office setting adjacent to an acute care setting , in the event a complication arose. Another advantage of LEEP cited in the literature , to see and treat at one office visit , is strongly argued from the United Kingdom data. I I However , one must remember that there are several striking and relevant differences between the gynecologic practice ofthe United Kingdom and the United States. The availability of cervical smear screening is less in the United Kingdom. As such , the prevalence of high-grade cervical neoplasia is greater. Comparatively , in the United States , a larger majority of the patients referred for colposcopy have lower grades of disease. As such , the incidence of unsuspected invasive cancer in excised specimens in the United Kingdom is as high as 1%-29毛 ， an incidence that is much lower in the United States. In addition , the low incidence of invasive cancer in the United States that is missed by examination , cytology , or colposcopy also argues against such treatment even in the most noncompliant patient. The clinic settings that exist today in this country are such that one can easily schedule separate diagnostic and treatment visits , with the hope of improving patient education and understanding and , hence , compliance with follow-up examinations. In an adolescent practice setting , the risks of cervical stenosis and infertility after an inappropriate treatment may be greater than the risk of undetected cervical cancer.
References 1. ACOG Committee Opinion: Role of loop electrosurgical
excision procedure in the evaluation of abnormal Pap test results, No. 195 , November 1997 2. Campion MJ: Modern Colposcopy: A Practical Approach. Treatment of Cervical Intraepithelial Neoplasia. Augusta, GA, Educational Systems, 1991 , chapter 14, p 1 3. Centers for Disease Control: Breast and cervical cancer surveillance-United States, 1973-1987. MMWR 1992~ 41:1 4. Centers for Disease Control: Premarital sexual experience among adolescent women-United States, 1978-1988. MMWR 1991~ 39:929
5. Brown RT, Hillard P: Adolescent Pap smear screening: yes or no. J Pediatr Adolesc Gynecol 1996~ 9:93 6. Crowther ME: Is the nature of cervical carcinoma changing in young women? Obstet Gynecol Surv 1994~ 50:71 7. LaVecchia C, Franceschi S, DeCarli A, et al: Sexual factors, venereal diseases and risk of intraepithelial and invasive cervical neoplasia. Cancer 1986~ 58:935 8. Townsend DE: Cryosurgery for CIN (review). Obstet Gynecol Surv 1979~ 34:828 9. Wright TC, Richart RM: Loop excision of the uterine cervix. CUff Opin Obstet Gynecol 1995~ 7:30 10. Prendiville W, Cullimore J, Norman S: Large loop excision of the transformation zone (LLETZ). Br J Obstet Gynaecol 1989~
96: 1054
11. Bigrigg MA, Codling BW, Pearson P, et al: Colposcopic
diagnosis and treatment of cervical dysplasia at a single clinic visit: experience of low voltage diathermy loop in 1000 patients. Lancet 1990~ 336:229
Opinions in Pediatric and Adolescent Gynecology Edited by Sally Perlm泊 ， MD , Division of Gynecology , Department of Surgery , Children's Hospital and the Department of Obstetrics , Gynecology , and Reproductive Medicine , Brigham and Women's Hospital , Harvard Medical School , Boston , Massachusetts; and by Mary Anne Jamieson , MD , Ki ngston , Ontario ,.Canada
This Opinions section, once again , is written by a single author but is meant to be provocative. It represents a sun1mary of a topic presented at a recent NASPAG conference. This issue did not result in a consensus of opinion at the end of the workshop. The ideologies presented represent the differing treatment philosophy that exists today among our peers who treat the abnormal pap smear in the adolescen t.
Treatment of the High-Grade Squamous Intraepithelial Lesion of the Cervix in Adolescents: Loop Electrical Excision Procedure or Cryotherapy In a 1997 Committee Opinion from ACOG , it was recommended that high-grade squamous intraepithelial lesion (HSIL) of the cervix should be considered a genuine cancer precursor.! These lesions should be treated within a reasonable time. However , the urgency with which the treatment should be offered and which treatment should be offered are less established. The progressive potential of HSIL in adult women is clearly and indisputably established. Two recent studies show this. In one study , a group of 60 women had highgrade atypia on their smear but refused biopsy or 仕eat ment. 2 After a mean interval of 5 years , 19 women had reported negative follow-up cytology. This is only by subjective repor t. However , invasive cancer had developed in 13 women , representing a 22% progression rate within a reasonably short period of time. In addition , a group from New Zealand reported on 300 women who had cytological evidence of high-grade preinvasive disease that were left untreated over a 20-year period. 2 A total of 369毛developed cervical cancer. Clearly , the risk of invasive cervical cancer in the adolescent is very low. Earlier age at first intercourse does seem to have an associated significant risk for invasive cancer in adults when separating those into sex before age 20 and those before age 30.3 When comparing national data between the 1970s and the 198郎 ， those adolescents that were sexually active before the age of 19 had almost doubled. 4 In addition , some investigators have postulated that , in some women , there may be an 1083-3188 © 1998 Lippincott-Raven Publishers
increased transit time to cervical cancer. 5 When this information is put together , it is easy to understand that , although rates of cervical cancer have leveled off, the rates of carcinoma in situ (CIS) in young women aged 20-29 years in this country and in others have increased. 6 ,7 Hence , at this juncture , most clinicians would agree that treatment of HSIL in the adolescent is warranted. The treatment modalities have evolved over the years because knowledge and understanding of the disease process have increased. Most clinicians today would agree that HSIL can be treated using conservative office or outpatient ablative or excisional procedures. Cryosurgery and loop electrical excision procedure (LEEP) are the most common treatment modalities used to treat HSIL in this country today. Is one method superior for the treatment of the adolescent with HSIL? Cryosurgery Cryosurgery involves freezing of cervical tissue using nitrous oxide (preferable) or carbon dioxide delivered to the lesion through a multisized probe attached to a delivery system? ,8 As with all other conservative therapeutic modalities , destruction of the entire transformation zone including epithelium in the lower portion of the endocervical canal is necessary. The aim is to minimize the risk of residual atypia or future development of disease in the lower endocervical cana l. Failure to destroy the entire transformation zone with adequate depth is the most common cause of cryotherapy failure. Residual or recurrent disease often occurs in the lower endocervical canal , occasionally escaping detection and proceeding to invasive cancer. The frequently used flat cryosurgery probes may predispose to this recurrence. The lower endocervical canal must be adequately treated. The training for performing this ablative treatment is much easier to effect than the excisional procedures. Hence , the clinician needs to be familiar with all of the equipment and select the correct probe that will ablate the entire lesion. Adequate treatment will frequently result in the squamocolumnar junction being inaccessible to colposcopic view after treatmen t. This finding is common and simply mandates adequate endocervical sampling in future screenIng.
98
Opinions in PAG
The efficiency of cryosurgery in the treatment of premalignant disease of the cervix has been extensi vely studied. Cure rates range from 27%-96%? It is generally accepted that the primary cure rate of cryosurgery for premalignant cervical disease is about 85%. After second or third treatment , the cure rate is more than 95%. The most important factor determining treatment outcome is the size of the lesion. Failure may occur because highgrade lesions are frequently larger , involving two or more quadrants of the cervix. Treatment failure also tends to occur in patients with scarred cervices or with lesions close to the endocervical cana l. Cryosurgery has high patient acceptability , which is important in effecting adequate therapy for the adolescen t. The technique requires no anesthesia. Uterine cramping and vasovagal phenomena may occur during the procedure. Bleeding is uncommon. Overall , significant complications are uncommon. This is very important in the adolescent population in which consistent compliance may be problematic. One can discuss results and effect treatment at the same visi t. The procedure requires little equipment and produces little discomfort and few side effects , thus minimizing any negative connotations that may inhibit the adolescent from returning. Finally , for the adolescent , the long-term side effects of cryosurgery even after repetitive procedures are much less profound than one aggressive or several repeated excisional procedures such as the LEEP. Several clinicians cite the advantage of cervical stenosis after repeated cryotherapy over a severely foreshortened cervix after one aggressive LEEP. 5 Loop Electrical Excision Procedure Cryosurgery , although simple and inexpensive , is associated with significant persistence or recurrence of all grades of cervical dysplasia. 2 Abnormal cytology after cryosurgery is worrisome particularly because often the endocervix is constricted and the squamocolumnar junction is inaccessible , requiring a second , most likely excision祉 ， procedure. Residual or recurrent disease in the endocervical canal posttreatment carries the potential for misdiagnosis because , by the time of diagnosis , it may have advanced to invasive cance r. This is particularly worrisome if the number of young women with CIS is IncreasIng. Hence , because the nU1l1ber of young women requiring colposcopy for SIL has increased to almost epidemic proportions , the need for more effective diagnostic and therapeutic modalities has spawned the introduction of the large loop excision of the transformation zone (LLETZ). 8 The entire transformation zone is excised using thin wire-loop electrodes and an electrosurgical generato r. In the United States , in part to promote consideration of wider usage beyond the cervical transformation zone , the ter 1l1 loop electrosurgical excision procedure , or LEEP , has been coined. Loop electrosurgical excision of the transformation
zone in the treatment of premalignant cervical disease combines the advantages of conservative ablative techniques with the safety of histopathological analysis of the entire specimen. Cartier9 developed wire electrodes , the precursor to our present modes of this therapy. Prendiville et al IOmodified the electrodes by developing larger electrodes and in1proved electrosurgical generators. The larger loop electrodes allow for excision of the entire transformation zone and the area of disease frequently in one pass. If the lesion is large or irregular or extends into the endocervical canal , several passes may be required with differing size or shape loop electrodes to adequately excise the lesion. The range of loop sizes and shapes permits considerable flexibility in tailoring the excision to the topography and the lesion. Typically , the LEEP is performed as an office procedure under local anesthetic. The significant discomfort associated with the earlier electrosurgical generators does not occu r. The amount of thermal damage to the specimen after LEEP is comparable with an expert excision using a continuous-wave CO 2 laser; however, the equipment is vastly less expensive and much simpler to use. Several distinct , theoretical advantages of LEEP over ablative approaches exis t. First , unlike cryosurgery or laser ablation , the affected tissue is removed rather than destroyed. Second , unsuspected invasive cancer will not be ablated. Last , submission of the entire specimen for histological evaluation adds an extra safety dimension to diagnosis of occult invasive cancer. Results to date regarding the efficacy of the LEEP are encouraging. Wright and Richart 9 tallied the results of 4 ,578 loop excision procedures. The overall success rate is 93.5% , similar to that for laser ablation and slightly better than that for a single cryosurgery treatment. Bigrigg et alII performed a 2-year follow-up study and reported a 5% rate of recurrence or persistence at 1 year of follow-up and 0.6% in the second yea r. Complications include perioperative discomfort or bleeding in 2%-7% of procedures. 9 Postoperatively , one can see hemorrhage in about 1%--4%; infection, discharge complaints similar to those reported with cryosurgery. 9 Rates of cervical stenosis and unsatisfactory colposcopy vary with the depth of the excision but range between 1%_9%.9 Effects on fertility and pregnancy are Ie
99
Opinions in PAG operating room given the constraints of our institution. This has lead to some difficulty with compliance and long lengths of time-to-procedure because parental consent is required. Other institutions have been able to avoid these problems by performing their procedures in an office setting adjacent to an acute care setting , in the event a complication arose. Another advantage of LEEP cited in the literature , to see and treat at one office visit , is strongly argued from the United Kingdom data. I I However , one must remember that there are several striking and relevant differences between the gynecologic practice ofthe United Kingdom and the United States. The availability of cervical smear screening is less in the United Kingdom. As such , the prevalence of high-grade cervical neoplasia is greater. Comparatively , in the United States , a larger majority of the patients referred for colposcopy have lower grades of disease. As such , the incidence of unsuspected invasive cancer in excised specimens in the United Kingdom is as high as 1%-29毛 ， an incidence that is much lower in the United States. In addition , the low incidence of invasive cancer in the United States that is missed by examination , cytology , or colposcopy also argues against such treatment even in the most noncompliant patient. The clinic settings that exist today in this country are such that one can easily schedule separate diagnostic and treatment visits , with the hope of improving patient education and understanding and , hence , compliance with follow-up examinations. In an adolescent practice setting , the risks of cervical stenosis and infertility after an inappropriate treatment may be greater than the risk of undetected cervical cancer.
References 1. ACOG Committee Opinion: Role of loop electrosurgical
excision procedure in the evaluation of abnormal Pap test results, No. 195 , November 1997 2. Campion MJ: Modern Colposcopy: A Practical Approach. Treatment of Cervical Intraepithelial Neoplasia. Augusta, GA, Educational Systems, 1991 , chapter 14, p 1 3. Centers for Disease Control: Breast and cervical cancer surveillance-United States, 1973-1987. MMWR 1992~ 41:1 4. Centers for Disease Control: Premarital sexual experience among adolescent women-United States, 1978-1988. MMWR 1991~ 39:929
5. Brown RT, Hillard P: Adolescent Pap smear screening: yes or no. J Pediatr Adolesc Gynecol 1996~ 9:93 6. Crowther ME: Is the nature of cervical carcinoma changing in young women? Obstet Gynecol Surv 1994~ 50:71 7. LaVecchia C, Franceschi S, DeCarli A, et al: Sexual factors, venereal diseases and risk of intraepithelial and invasive cervical neoplasia. Cancer 1986~ 58:935 8. Townsend DE: Cryosurgery for CIN (review). Obstet Gynecol Surv 1979~ 34:828 9. Wright TC, Richart RM: Loop excision of the uterine cervix. CUff Opin Obstet Gynecol 1995~ 7:30 10. Prendiville W, Cullimore J, Norman S: Large loop excision of the transformation zone (LLETZ). Br J Obstet Gynaecol 1989~
96: 1054
11. Bigrigg MA, Codling BW, Pearson P, et al: Colposcopic
diagnosis and treatment of cervical dysplasia at a single clinic visit: experience of low voltage diathermy loop in 1000 patients. Lancet 1990~ 336:229