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Keywords:

  • Cervix biopsy;
  • cone volume;
  • laser;
  • LLETZ

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References

Please cite this paper as: Phadnis S, Atilade A, Young M, Evans H, Walker P. The volume perspective: a comparison of two excisional treatments for cervical intraepithelial neoplasia (laser versus LLETZ). BJOG 2010;117:615–619.

Objective  To compare two excisional treatments, laser cone biopsy and large loop excision of the transformation zone (LLETZ), in terms of the volume of tissue removed, and to determine the relation between the height and the total volume of the cone specimen.

Design  Retrospective cross-sectional study.

Setting  Large teaching hospital in London.

Population  A total of 1136 eligible excisional treatments (laser cone or large loop excision of the transformation zone, LLETZ).

Methods  Eligible excisional treatments (laser cone or LLETZ) performed between 1 January 2002 and 31 December 2007 in our colposcopy unit were identified using the Infoflex® database. The total volume of the cone biopsy was calculated mathematically using the data provided in the histopathology reports.

Main outcome measures  The volume of the cone biopsy was compared with the technique of excision and the histology grades.

Results  Three hundred and thirty-nine laser cone biopsies were performed, whereas 797 LLETZ biopsies were recorded, during the study period. There was no difference in the mean age in the two groups. However, there is a proportional increase in the volume of the cone as the height of the cone increases, and a significant number of the values are skewed, suggesting that the diameter of the base of the cone contributes significantly to the total volume. Laser cone biopsies (median volume 1.84 cm3, 95% CI 1.98–2.54 cm3) account for a larger volume of tissue excised compared with LLETZ (median volume 0.78 cm3, 95% CI 0.91–1.02 cm3) (< 0.0001). This relationship is not altered when the two procedures are stratified for grade of lesion, i.e. excision for low-grade cervical intraepithelial neoplasia (CIN) (laser median volume 1.55 cm3, 95% CI 1.46–2.06; LLETZ median volume 0.62 cm3, 95% CI 0.73–0.88 cm3) (< 0.0001) or high-grade CIN (laser median volume 1.84 cm3, 95% CI 2.11–2.53 cm3; LLETZ median volume 0.82 cm3, 95% CI 0.94–1.07 cm3) (< 0.0001).

Conclusions  The volume of cervical tissue removed during laser conisation is significantly more than that removed with LLETZ. The indication of the cone biopsy does influence the volume of tissue removed.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References

Laser conisation and large loop excision of transformation zone (LLETZ) are the two most common and preferred excisional methods for treatment of cervical intraepithelial neoplasia (CIN). A study by Bruinsma et al.1 suggested that diagnosis of precancerous change in the cervix, regardless of whether treatment was carried out, was associated with an increased risk of preterm birth. Furthermore, excisional treatment for CIN was associated with preterm birth. A meta-analysis by Kyrgiou et al.2 suggested adverse obstetric outcomes in women having excisional treatment compared with those having destructive treatment.

The exact aetiology of preterm birth after an excisional treatment to the cervix is unknown. Sadler et al.3 reported that women with a cone height of ≥1.7 cm have a three-fold increase in the risk of preterm prelabour rupture of membranes (PPROM) compared with a cohort of untreated women. It is assumed that there is a true relationship between the height of the cone and pregnancy-related complications. It is possible, however, that the total volume of the cone and not just the height could be related to the outcome. The height of the cone may not be a true representation of the volume of tissue removed during the excisional biopsy.

The objective of our study was to investigate the relationship between the height and the volume of the excisional specimen. We also compared two excisional treatments for CIN, laser cone biopsy and LLETZ biopsy, in terms of the total volume of tissue removed.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References

A retrospective cross-sectional study was performed using the Infoflex database® (Chameleon Information System, Rickmansworth, UK). This database contains the results of clinical evaluation and outcomes for women attending colposcopy clinics at The Royal Free Hospital, London, UK. Women included in the study were those who underwent a cervical excisional biopsy between January 2002 and December 2007, and where there was complete information on the histology of the biopsy (Figure 1).

image

Figure 1.  Study design.

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Women who had a laser or LLETZ excisional biopsy of the cervix were identified. The histology reports were accessed to determine the dimensions of the cone biopsy. The transverse diameter (a), longitudinal diameter (b) and depth (c) of the cone biopsy were noted. We postulated that the cone specimen obtained was a hemiellipsoid, as the parameters a, b and c were often unequal. Therefore, the volume of the specimen was calculated using the mathematical formula: 1/2 × 4/3 × π × a/2 × b/2 × c (as the height of the cone is a radius of the ellipsoid rather than a diameter).

The data in each of the two excisional biopsy groups was classified according to the grade of histology. The outcomes were compared in terms of volume of the cone biopsy between the subgroups using the Mann–Whitney U test. The correlation between the height and volume of cone biopsy was calculated. The analysis of data was performed using SPSS (Statistical Package for Social Sciences, Chicago, IL, USA) v13 for Windows®.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References

During the study period, 1250 excisional biopsies of the cervix were performed in our colposcopy unit. As a result of incomplete data, 114 (9%) were excluded from the study. A total of 797 (63.8%) LLETZ biopsies were performed under local anaesthesia, whereas 339 (27.1%) laser cone biopsies were performed under general anaesthesia. The indications for inpatient laser cone biopsy in our unit are: large-volume lesion, suspected microinvasion, cervical glandular lesions (CGIN), re-treatments and patient anxiety.

The median volume of the cone when a laser cone biopsy was performed was 1.84 cm3 (range 0.12–10.11 cm3, 95% CI 1.98–2.54 cm3), whereas the median volume of the cone biopsy obtained by performing an LLETZ was 0.78 cm3 (range 0.02–8.06 cm3, 95% CI 0.91–1.02 cm3). When a laser cone biopsy was performed for a low-grade CIN, the median volume of the cone was 1.55 cm3 (range 0.12–6.28 cm3, 95% CI 1.46–2.06 cm3), whereas the cone for an LLETZ biopsy was 0.62 cm3 (range 0.02–5.41 cm3, 95% CI 0.73–0.88 cm3). Comparing the two excisional techniques when performed for high-grade CIN, the median volume of a laser cone biopsy was 1.84 cm3 (range 0.21–2.53 cm3, 95% CI 2.11–2.53 cm3), whereas that of an LLETZ biopsy was 0.82 cm3 (range 0.06–7.85 cm3, 95% CI 0.94–1.74 cm3). There was a statistically significant difference in the volumes of the cones obtained by the two excisional techniques, regardless of the indication (whether a low-grade or a high-grade CIN) (< 0.0001) (Table 1). Thus, a laser cone biopsy accounts for a larger volume of tissue excised compared with an LLETZ cone biopsy. There was a statistically significant difference when the volume obtained in a laser cone biopsy performed for a patient anxious to have an outpatient procedure (median volume 1.25 cm3, range 0.23–9.11 cm3, 95% CI 1.37–2.82 cm3) was compared with the LLETZ group (median volume 0.78 cm3, range 0.02–8.06 cm3, 95% CI 0.91–1.02 cm3) (Mann–Whitney U = 8935, n1 = 35, n2 = 797, two-tailed P = 0.003). The median height of the laser biopsy cone was 2 cm (range 0.7–3 cm, 95% CI 1.92–2.01 cm), whereas it was 1.6 cm (range 0.6–3.4 cm, 95% CI 1.65–1.7 cm) for LLETZ. There was a statistically significant difference between the two groups (Mann–Whitney U = 81833, n1 = 339, n2 = 797, two-tailed < 0.001).

Table 1.   Cone height and volume according to the grade of cervical intraepithelial neoplasia (CIN)
Grade of CINMedian cone heightMedian cone volume
Laser
CIN11.8 cm, 95% CI 1.68–1.87 cm1.55 cm3 95% CI 0.91–1.02 cm3
CIN2–32.0 cm, 95% CI 1.95–2.06 cm1.84 cm3 95% CI 2.11–2.53 cm3
Loop
CIN11.5 cm 95% CI 1.55–1.64 cm0.62 cm3 95% CI 0.73–0.88 cm3
CIN2–31.6 cm 95% CI 1.66–1.73 cm0.82 cm3 95% CI 0.94–1.74 cm3

A scatter plot of cone volume (y-axis) in relation to cone height (x-axis) revealed a linear relation. The Spearman’s rank order correlation (ρ) was 0.65 [df = 1134, critical one-sided t-value (5%) = 1.65] indicating a strong correlation between the volume and height of the cone (Figure 2).

image

Figure 2.  A scatter plot showing the relationship between the height and the volume of the cone.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References

A cone, by definition, is a three-dimensional geometric shape consisting of all line segments joining a single point (the apex or the vertex) to every point of a two-dimensional figure (the base). The axis of a cone is the line joining the apex to the centre of the base. In elementary geometry, the base is a circle and the axis is perpendicular to the plane of the base, and therefore cones are assumed to be right circular. In an oblique cone, the line that joins the apex to the centre of the circular base is not the axis. A cone with its apex cut off by a plane parallel with its base is called a truncated or a frustum cone. In general, the base of the cone may take any shape and the apex may lie anywhere. However, it is often assumed that the base is bounded and has a non-zero area, and that the apex lies outside of the plane of the base. Circular cones and elliptical cones have, respectively, circular and elliptical bases. If the axis of the cone is at right angles to its base then it is said to be a right cone, otherwise it is an oblique cone. The base radius of a circular cone is the radius of its base; often this is simply called the radius of the cone. The volume (V) of any conic solid is one-third the area of the base (b) times the height (h, the perpendicular distance from the base to the apex), expressed as V = 1/3 × b × h. For a circular cone with a radius (r) and height (h), the formula for volume becomes V = 1/3 × π × r2 × h.4,5

In practice, we observed that various shapes of cone biopsies can be obtained dependant on the clinical indication. Whereas it is common to perform a ‘saucer-shaped’ cone biopsy for a low-grade CIN, particularly in young women with a wide ectocervical lesion, a ‘cylindrical’ cone biopsy may be performed if a cervical glandular intraepithelial neoplasia (CGIN) or a microinvasive carcinoma of the cervix is suspected. However, most cone biopsies obtained in clinical practice are circular cones: often the transverse diameter and the longitudinal diameter of the specimen are of an unequal size. Therefore, we postulated that a cone biopsy of the cervix is geometrically a hemiellipsoid rather than a right circular cone. We calculated the volume of the specimens, irrespective of the technique used, using the formula: 1/2 × 4/3 × π × a/2 × b/2 × c/2 (where a = transverse diameter, b = longitudinal diameter and c = depth of the specimen).

There is emerging evidence in the literature suggesting pregnancy-related morbidity after excision treatment for CIN. Although the exact aetiology is not known, the height of the cone biopsy has been shown to be directly related to the risk of PPROM and preterm labour. This may seem logical, as the deeper the cone biopsy, the greater the risk of damage to the internal os of the cervix, and thus the greater the risk of preterm labour. Bruinsma et al.1 reported 11.5% of women had a preterm delivery in a cohort of 1951 treated women, and 3.5% of treated women delivered before 32 weeks. Therefore, in terms of burden on health resources, this relationship seems to be significant. Kyrgiou et al. found that excisional treatments for CIN were significantly associated with adverse obstetric outcomes. In their meta-analysis, LLETZ had a relatively higher risk of pregnancy-related morbidity than laser conisation.2 There is a paucity of knowledge regarding the calculation of cone biopsy volume, and also its influence on pregnancy-related complications. Leiman et al.6 estimated the cone volume and found that there was an increased incidence of spontaneous miscarriage and preterm labour when the volume of the cone was more than 4 cm3. Sadler et al.3 found no difference between laser and LLETZ biopsy in the height of the cones obtained, but did find that preterm labour was more common after laser cone biopsy. Acharya et al.7 report an increase in total preterm birth among women treated with a 25-mm loop compared with controls. Arbyn et al.8 reported that all excisional treatments raise the risk of perinatal morbidity, but that the risk is significantly greater in the cold-knife conisation group, and there may be an increased risk after LLETZ. There have been numerous reports following the meta-analysis by Kyrgiou et al. supporting the evidence that excisional treatments for CIN raise the risk of preterm labour and delivery, low-birthweight neonates and neonatal complications.9–12 We need a clear understanding of the aetiology of this morbidity in relation to an excision biopsy of the cervix.

It might be suggested that the total volume of the cone biopsy may be as significant as the height. In this retrospective study, we compared the two common excision techniques, laser cone biopsy and LLETZ biopsy, in terms of the total volume of tissue removed. Our study revealed that in comparison with LLETZ biopsy, the laser cone biopsy tends to excise significantly more tissue (P < 0.0001). This relation is not altered when the cone volume is graded for the degree of CIN excised. As described earlier, in our colposcopy unit, a laser cone biopsy is performed under general anaesthesia. The indications for laser cone biopsy are a large transformation zone, a large lesion, or suspicion of CGIN or microinvasive carcinoma of the cervix, all of which might imply the requirement for an increased volume of cone biopsy. Re-treatment might well require a larger volume, and anxiety should not affect the volume of removed tissue. When we compared a subgroup of laser conisation performed for women who were perceived to be too anxious to have an outpatient procedure with the LLETZ group, we observed a statistically significant difference in the cone volumes, with laser conisation associated with a larger volume compared with LLETZ. Although it seems that laser cone biopsy as a technique is responsible for the removal of a large volume of cervical tissue, the indications for which this procedure is performed may influence this result.

There was a strong correlation between the height and volume of a cone biopsy, but there were some values that were skewed. This meant that although the height of the cone was a significant determinant of the volume, the surface area of the base of the cone was equally contributory. Thus, although the height of the cone may be used as a surrogate value for the volume, in many cases it will not be an accurate substitute. However, it remains to be seen whether the height of the cone or the volume removed is more important in relation to future pregnancy outcome. Given the close correlation between these measurements it is unlikely that any study will be large enough to separate these effects. What is important is that when treatment is required it should be effective, and sufficient tissue must be removed to achieve this objective. If cone volume proves to be a significant variable in the risk of preterm labour and pregnancy-related complications, then it may be necessary to review the use of excisional treatment, particularly for low-grade lesions.

The retrospective analysis of data limits the scope of this study. Data was not collected in terms of future pregnancy outcomes of the patients included in this study. Such data collection is often difficult, and population mobility restricts accurate analyses. A further longitudinal study will be required to prove the exact relationship between volume of the cone and pregnancy-related morbidity.

In conclusion, the volume of cervical tissue removed during laser conisation is significantly more than with an LLETZ biopsy. The indication of the cone biopsy does influence the volume of tissue removed. It is important that current studies on future pregnancy-related complications stratify for cone volume and technique. We are attempting to do this via a national study, which is being designed at this time.

Contribution to authorship

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References

PGW, HE and MPAY conceived the idea and design. SP and AA collected and analysed the data. SP prepared the manuscript under the supervision of PGW.

Details of ethics approval

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References

Ethics approval was not sought as this was a retrospective analysis of data.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References
  • 1
    Bruinsma F, Lumley J, Tan J, Quinn M. Precancerous changes in the cervix and risk of subsequent preterm birth. BJOG 2007;114:7080.
  • 2
    Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, Prendiville W, Paraskevaidis E. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet 2006;367:48998.
  • 3
    Sadler L, Saftlas A, Wang W, Exeter M, Whittaker J, McCowan L. Treatment for cervical intraepithelial neoplasia and risk of preterm delivery. JAMA 2004;291:21006.
  • 4
    Harris JW, Stocker H “Cone”. Handbook of Mathematics and Computational Science. New York: Springer-Verlag; 1998. pp. 1045.
  • 5
    Hilbert D, Cohn-Vossen S “The Cylinder, the Cone, the Conic Sections,and Their Surfaces of Revolution”. Geomtery and Imagination. New York: Chelsea; 1999. pp. 711.
  • 6
    Leiman G, Harrison NA, Rubin A. Pregnancy following conisation of the cervix: complications related to cone size. Am J Obstet Gynecol 1980;136:148.
  • 7
    Acharya G, Kjeldberg I, Hansen SM, Sorheim N, Jacobsen BK, Maltau JM. Pregnancy outcome after loop electrosurgical excision procedure for the management of cervical intraepithelial neoplasia. Arch Obstet Gynecol 2005;272:10912.
  • 8
    Arbyn M, Kyrgiou M, Simeons C, Raifu AO, Koliopoulos G, Martin-Hirch P, et al. Perinatal morbidity and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: a meta-analysis. BMJ 2008;337:a1284.
  • 9
    Albrechtsen S, Rasmussen S, Thoresen S, Irgens LM, Iversen OE. Pregnancy outcome in women before and after cervical conisation: population based cohort study. BMJ 2008;337:a1343.
  • 10
    Jakobsson M, Gissler M, Sainio S, Paavonen J, Tapper AM. Preterm delivery after surgical treatment for cervical intraepithelial neoplasia. Obstet Gynecol 2007;109:30913.
  • 11
    Sjoborg KD, Vistad I, Myhr SS, Svenningsen R, Herzog C, Kloster-Jensen A, et al. Pregnancy outcome after cervical cone excision: a case control study. Acta Obstet Gynecol Scand 2007;86:4238.
  • 12
    Nohr B, Tabor A, Frederiksen K, Kjaer SK. Loop electrosurgical excision of the cervix and the subsequent risk of preterm delivery. Acta Obstet Gynecol Scand 2007;86:596603.