ORIGINAL RESEARCH ARTICLE: CERVIX AND HPV
Recurrence in Cervical High-Grade Squamous Intraepithelial
Lesion: The Role of the Excised Endocervical Canal Length—
Analysis of 2,427 Patients
Andresa Ines Foggiatto, MD,1 Newton Sergio de Carvalho, PhD, MD,1
Fernanda Villar Fonseca, PhD, MD,2,3 and Carlos Afonso Maestri, PhD, MD2,3
Objective: This study aimed to evaluate the influence of the excised canal
length on relapse rates of cervical high-grade squamous intraepithelial le-
sion (HSIL) treated by loop electrosurgical excision procedure and to find
a cut-off point, above which lower recurrence rates could be observed, with
low probability of compromising future obstetric outcome, and the rela-
tionship with other individual factors related to HSIL recurrence.
Method: This was a retrospective cohort study of 2,427 women diag-
nosed with cervical intraepithelial neoplasia CIN2+ who underwent cervi-
cal conization using the high-frequency loop electrosurgical excision pro-
cedure surgery technique, to analyze the role of endocervical canal length
associated with individual factors in the recurrent disease after CIN2+ treat-
ment and determine a cut-off point for the excised canal length needed to
decrease the risk of disease relapse.
Results: In 2,427 cases, the relapse rate of HSIL treated was 12%. Com-
promised margins of conization, HIV+, and endocervical canal length were
related directly to relapses ( p < .001). The cut-off point, by receiver oper-
ating characteristic curve, to calculate the endocervical canal length related
to relapses was 1.25 cm of canal excised. Canal length of less than 1.25 cm
increased the recurrence rate 2.5 times. Compromised margins and HIV+
increased recurrence rates by more than 5 times.
Conclusion: Cervical HSIL recurrence was directly related to the endo-
cervical canal length: excised canal length of 1.25 cm or more decreases re-
currence rate; HIV and compromised margins increase the chance of recur-
rence by more than 5 times.
Key Words: high-grade squamous intraepithelial lesion, conization,
loop electrosurgical excision procedure, recurrence,
cervical intraepithelial neoplasia, canal length
(J Low Genit Tract Dis 2023;27: 1–6)
C ervical cancer is a major public health problem in Brazil and
in developing countries and is associated with persistent in-
fection with human papillomavirus (HPV) oncogenic types, espe-
cially 16 and 18, responsible for approximately 70% of
cervical cancers.1,2
Cervical malignancies are preceded by a long phase of
preinvasive disease, jointly denominated as cervical intraepithelial
1
Gynecology and Obstetrics Department, Federal University of Parana, Curi-
tiba, Parana, Brazil; 2Gynecology Department, Positivo University, Curitiba,
Parana, Brazil; and 3Cervical Pathology Department, Erasto Gaertner Cancer
Center Hospital, Curitiba, Parana, Brazil
Reprint requests to: Fernanda Villar Fonseca, PhD, MD, R. Dr Ovande do
Amaral, 201-Jardim das Américas, Curitiba, Paraná, Brazil. CEP
81520-060. E-mail: fvfonseca74@gmail.com
The authors have declared they have no conflicts of interest.
Andresa Ines Foggiatto ORCID: 0000-0002-4733-0256.
Newton Sergio de Carvalho ORCID: 0000-0001-7561-4566.
Fernanda Villar Fonseca ORCID: 0000-0002-0162-9893.
Carlos Afonso Maestri ORCID: 0000-0003-0200-9802.
Ethics committee status: approved on March 28, 2017.
This study evaluated the predictive factors that could influence persistence or
recurrence of high-grade squamous intraepithelial lesion after treatment
with loop electrosurgical excision procedure in 2,427 women, including the
role of endocervical canal length.
© 2022, ASCCP
DOI: 10.1097/LGT.0000000000000708
Journal of Lower Genital Tract Disease • Volume 27, Number 1, January 2023
Copyright © 2022 ASCCP. Unauthorized reproduction of this article is prohibited.
neoplasia (CIN). Richart (1967) classified CIN as 1, 2, and 3 de-
pending on the proportion of epithelial thickness that presents ma-
ture and differentiated cells. The Bethesda System (1992) created
the term squamous intraepithelial lesion (SIL), which comprised
low-grade and high-grade (HSIL) lesions. Low-grade lesions in-
clude flat condylomatous changes (HPV) and low-grade CIN
(CIN1), whereas high-grade intraepithelial lesions (HSIL) com-
prise CIN 2 and 3.3,4
Most low-grade CIN regress in relatively short periods or do
not progress to high-grade lesions. High-grade CINs are more
likely to progress to invasive cancer.3
Studies show that persistence of high-risk oncogenic HPV
may determine progression to more severe stages of cervical dis-
ease. The risk for disease progression seems to be associated with
the host HPV cycle.3,5–9 The natural history of HPV in the human
host has some points not yet fully elucidated. Human papillomavi-
rus infection is very common among young women during sex
life; approximately 70% of women will have contact and/or tran-
sient infection because of it. Despite these high rates of infection,
few infected women will develop cervical cancer.8
The treatment of high-grade lesions, when chosen, can be
performed by destructive methods such as cauterization or exci-
sion, with preference for excision by obtaining a surgical speci-
men that rules out the possibility of invasion. The most commonly
used surgical technique is conization, which can be performed by
cold scalpel method or by electrosurgery technique: the large loop
excision of the transformation zone and loop electrosurgical exci-
sion procedure (LEEP), also known in Brazil as excision
transformation zone.10
Studies consider residual disease that were identified during
the first year after conization or recurrence when it happens after
this period.11,12
Some known factors related to residual neoplasia or recur-
rence after conization are the degree of CIN, compromised exci-
sion margins and glandular involvement in the conization product,
age, race, number of pregnancies and deliveries, socioeconomic
status, smoking, marital status, nonvaccination against HPV, and
presence of high-risk HPV.5–15
The CIN relapse rates after conization by LEEP range from
5% to 30%, and patients need follow-up and sometimes retreatment
when lesions are identified.14–20 Major relapse-related complica-
tions are compromised margins and associated HIV infection.10
Some studies have shown that the main complications related to
the removal of the canal length would be an increase in future ob-
stetric comorbidities such as premature delivery, premature
amniorrhexis, and low birth weight.21,22
On review of the literature, no studies were found that evalu-
ated a cut-off point of the length of the resected canal with recur-
rence rates. On the other hand, there are many studies that demon-
strate the importance of canal length in those who underwent sur-
gery with later pregnancy. In these studies, there are data that
report that greater length of the removed canal related to the occur-
rence of premature birth.23,24 Thus, the objective here is to evalu-
ate the influence of the excised canal length on relapse rates of
1
Foggiatto et al. Journal of Lower Genital Tract Disease • Volume 27, Number 1, January 2023
disease and to find a cut-off point above which lower recurrence
rates could be observed associated with low probability of
compromising the obstetric outcome.
MATERIALS AND METHODS
This is an observational, descriptive, retrospective, longitudi-
nal study of women diagnosed with CIN2+ (CIN 2 or 3/HSIL)
who underwent cervical conization using the high-frequency
LEEP surgery technique at the Cervical Pathology Service at
Erasto Gaertner Cancer Center in Curitiba, Paraná, Brazil, from
January 2009 to December 2016. The project was approved by
the research ethics committee.
Patient Selection, Data Collection, and Sample
Patient Selection. From January 2009 to December 2016,
4,016 patients who underwent the cervical conical resection
process were included. In this population, the following criteria
were applied:
- Inclusion criteria: patients treated at the Cervical Pathology
Service, with cytohistological diagnosis through Pap smear
and subsequent colposcopy-directed biopsy confirming CIN 2
or 3. This cohort was submitted to a conical cervical
resection procedure.
FIGURE 1. Flowchart 1 - Disease cut-off point and recurrence analysis.
2 © 2022, ASCCP
Copyright © 2022 ASCCP. Unauthorized reproduction of this article is prohibited.
- Exclusion criteria: colposcopy-directed biopsy showing a dif-
ferent report of CIN 2 or 3 (excluding reports of cervicitis and
microinvasive cancer); patients with clinical follow-up shorter
than 18 months.
Data Collection. Epidemiological data were collected only by
the researcher group through a review of the electronic medical
records of the patients included in the study. Epidemiological
data (age, smoking, HIV seropositivity, clinical follow-up after
conization), histological data (histological diagnosis of cervical
biopsy), and data related to the treatment performed (conization
technique, conization analysis of the product margins, piece
volume, and canal length) were collected.
Study Design. The global sample of patients selected by the
inclusion and exclusion criteria resulted in 2,427 patients. This
can be seen in Flowchart 1 (global patient sample).
Conization Technique and Canal
Length Assessment
The conization technique was performed using LEEP in all
cases, according to the protocol of the Cervical Pathology Service,
in which lesions considered too large and/or deep were previously
determined for the classical technique. The procedure was
Journal of Lower Genital Tract Disease • Volume 27, Number 1, January 2023 Risk Factors to HSIL Recurrence

TABLE 1. Global Sample Epidemiological Data (n = 2,427 TABLE 3. Relationship of Data Related to the Surgical Specimen
Cases) With HSIL Relapses/Recurrence

Age, y 40 ± 11 (18–93) Recurrence

Parity 2 ± 1.8 children (0–13) NO YES
Smokinga Yes 668 (27.5%) Average DP Average DP p
No 1,755 (72.4%)
HIVa Yes 56 (2.6%) Excised canal length, cm 2.75 0.78 2.57 0.86 0.01
No 2,317 (97.3%) Total volume of the 5.28 4.44 4.88 3.63 0.16
excised piece, cm3
Biopsy histology CIN 2 1,288/1,699 (75.8%)
CIN 3 411/1,699 (24.2%) Data source: the authors (n = 2,427 cases).

Data source: the authors.

Global sample: n = 2,427 cases.
a
In 0.1% of cases, these data were not accessible, as this was a retrospective
study.
performed using the LEEP classical technique described by
Prendiville et al.24 in 1989, under local anesthesia in all cases.
Surgery was performed in an outpatient setting, and the pa-
tients returned for postoperative review within 20 days and there-
after, semestral clinical follow-up.
The canal length was measured with a millimeter ruler by cal-
culating the upper edge of the outer margin with the lower edge.
The volume of uterine cervix removed was calculated by mul-
tiplying the length by the height by the width of the removed piece.
relapse, a descriptive analysis was performed. Data were
presented by distribution of absolute and relative fre-
quencies, and comparisons between relapses and
nonrelapses were performed with the χ 2 test.
3. Cut-off point for analysis: the receiver operating characteris-
tic (ROC) curve was used to estimate a cut-off point where the
chance of relapse could be higher.
4. Association: possible associations between canal length and
relapse were verified by binary logistic regression. For the ad-
justed analyses, factors such as age, parity, and smoking
were included.

Statistical Data Analysis RESULTS

Statistical procedures were performed using software SPSS From January 2009 to December 2016, 4,016 conizations
version 24.0 (IBM, Armonk, NY) and STATA version 13.0 were performed at the Cancer Center. After exclusion criteria were
(StataCorp LLC, College Station, TX), with p set at 0.05, follow- applied, 2,427 patients were selected.
ing these strategies: Of the 2,427 patients, 311 (12.8%) relapsed and 2,116
(87.2%) did not relapse, as shown in Flowchart 1 (Figure 1).
1. Data normality: verified by the Kolmogorov-Smirnov test. The average age was 40 ± 11.5 years (18–93), the parity was
2. To observe if there was any relationship between the 2 ± 1.8 children (0–13). Smoking was present in 668 women and
length of the cervical canal removed and the chance of HIV was positive in 2.6% (56) of the patients.
Free margins were found in 87.3% (2,119) of the cases and
compromised in 12.6% (308). Of the compromised margins,
TABLE 2. Relationship of Data Related to the Surgical Specimen 42.85% were ectocompromised, 43.83% endocompromised, and
With HSIL Relapses/Recurrence ( p Value to Recurrence) in 12.33% of them, both margins were compromised. In patients
Variable Results p
Age, y 40 ± 11 (18–93) 0.01 TABLE 4. Comparative Data Between Cases of Recurrence and
Parity 2 ± 1.8 children 0.06 Nonrecurrence in Relation to the Canal Length Excised
(0–13)
Smokinga Yes 668 (27.5%) 0.45 Recurrence Recurrence rate
Excised canal
No 1,755 (72.4%) length Yes No (%)
HIVa Yes 56 (2.6%) 0.001 <1.25 cm 17/61 44/61 28%
No 2,317 (97.3%) 1.25–2 cm 64/390 326/390 16%
Biopsy histology CIN 2 1,288/1,699 (75.8%) 0.34 2–2.5 cm 71/663 592/663 11%
CIN 3 411/1,699 (24.2%) >2.5 cm 160/1,313 1,154/1,313 12%
Conization Free 2,116 (87.3%) 0.001
margins
Note: Using ROC curve, 1.25 cm was the cut-off point where the
Involved 308 (12.6%) chance of recurrence rates can be higher.
Average length 2.7 cm ± 0.8 cm 0.01 Recurrence rate
of the
excised canal No Yes p All
Average volume 5.2 cm3 ± 4.3 cm3 0.16 n % n % N %
of the Excised canal <1.25 cm 44 1.8 17 0.7 0.001 60 2.5
excised piece length
a
≥1.25 cm 2,072 85.4 295 12.2 2,367 97.5
In 0.1% of cases, these data were not accessible, as this was a retrospec-
tive study. Data source: the authors.

© 2022, ASCCP 3

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Foggiatto et al. Journal of Lower Genital Tract Disease • Volume 27, Number 1, January 2023

FIGURE 2. The ROC curve for all sample/cut-off point for the canal length from which the HSIL recurrence rate increases.

with compromised margins, relapses occurred in 116 (37.7%) and
in 196 (9.2%) in those with free margins, and it was statistically
significant ( p < .001).
The epidemiological data and those related to the product of
conization can be seen in Table 1.
Epidemiological data show that age and parity were sta-
tistically significant to disease recurrence, whereas smoking
was not. The presence of HIV was demonstrated to be highly
significant in association with relapsing. Regarding the ex-
cised specimen data, it was observed that the biopsy histolog-
ical report and volume were not related to recurrence rates. On
the other hand, margin impairment and canal length were directly
related to the chance of relapse. All these data can be seen in
Table 2.
Recurrence occurred in 311 of the 2,427 patients, repre-
senting 12.8%. The average time to relapse was 13 months
±12.5 months. Relapse was 52% at 10 months, 62.5% at
12 months, and 80.4% at 18 months, considering that only pa-
tients who had follow-up beyond 18 months were included.
The positivity of HIV was a significant factor for recurrence
( p < .001), with relapse occurring in 12% of seronegative and
43% of seropositive patients.
The study showed that there was a significant difference
between relapses and nonrelapses in relation to canal length,

TABLE 5. The Recurrence Probability (OR) for Treated HSIL in Relation to Canal Length, HIV Seropositivity, and Margins of the
Conization Product

Raw analysis Adjusted analysis

OR 95% CI p OR 95% CI p
Canal length ≥1.25 cm 1 — — 1 — —
<1.25 cm 2.55 1.42 – 4.58 0.002 2.40 1.26 – 4.56 0.007
HIV Negative 1 — — 1 — —
Positive 6.67 3.93 – 11.29 0.001 5.65 3.20 – 9.97 0.001
Compromised margin Free 1 — — 1 — —
Compromised 0.99 4.55 – 7.87 0.001 5.83 4.38 – 7.76 0.001
Adjusted analysis for all factors: p < .05.
OR indicates odds ratio.
Data source: the authors.

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Journal of Lower Genital Tract Disease • Volume 27, Number 1, January 2023
although the analysis of the total volume of the piece did not
show such association, as can be seen in Table 3.
As evidenced in the literature that the chance of relapsing is
higher in patients with compromised margins and HIV,11 based
on the analysis of the canal length as a function of the relapse rate,
these patients were excluded, comprising a population that was
called “purified population.” It could be argued that the possibility
of greater margin compromise would be associated with the
shorter length of the removed canal. After statistical analysis, it
was shown that there was a correlation between excised cervical
canal length and chance of relapsing.
We observed that the resected volume of the piece was not
statistically significant; therefore, we focused on the length of
the canal, and that was the main object of the study analysis as
shown in Table 4.
To evaluate if there was a certain cut-off point of the excised
canal length that was associated with higher chance of recurrence,
the data were analyzed using an ROC curve, as can be seen in
Figure 2. The graph shows the ROC curve of the general popula-
tion showing that 1.25 cm or longer of canal resection would have
a lower chance of recurrence.
In an attempt to evaluate the chance of relapse in relation to
the factors listed in Table 5, we observed the odds ratio of each
factor as a function of recurrence. The study demonstrated that
the presence of compromised margins increases the risk of relapse
by 5.99 times ( p < .001; 95% CI = 4.55–7.87). The presence of
HIV increases the risk of relapse by 6.67 times ( p < .001; 95%
CI = 3.93–11.29). When the length of the excised canal is shorter
than 1.25 cm, the risk of recurrence increases by 2.55 times (95%
CI = 1.42–4.58).
As limiting factors, we suggest that this was a retrospective
study, in which the pieces were evaluated and the canal length
was measured without a planned association with recurrence rates.
Moreover, the fact that we did not link to the location of the le-
sions, if ectocervical or endocervical (intracanal), may suggest
to us that in the latter, canal length value may be underestimated.
The procedures were performed by various health profes-
sionals, and the anatomopathological specimen was evaluated by
different sets of pathologists; this interoperator/interobserver
“bias” is likely overcome by sample size.
DISCUSSION AND CONCLUSIONS
Because of the dilemma between the lower chance of recur-
rence of cervical lesion (CIN) and the possibility of increasing
the rate of prematurity, the excision of the canal should not be less
than that sufficient to prevent recurrence of the lesion (high-grade
CIN) and not greater than that which could increase the risk of
prematurity rate.
Therefore, based on this rationale, the goal of this study and
as-found novelties has shown the direct relationship between the
measurement of the excised (resected) canal length and the recur-
rence after conization.
Among the excised canal measurements, the cut-off point of
1.25 cm was obtained, below which recurrence rates increased by
2.55 times, and these data have not yet been found in the literature.
Among the perspectives, it is important to highlight that be-
sides countless variables already shown in the literature, which in-
crease recurrence after conization, the length of the canal also pre-
sents this assertion.
This study opens perspectives so others can evaluate this
finding in other samples and other populations (the canal length
cut-off point).
In addition, because we know that the shorter the excised ca-
nal length, the better the obstetric future, we believe that with this
© 2022, ASCCP
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Risk Factors to HSIL Recurrence
defined cut-off point, we may have contributed to the reduction of
obstetric comorbidities and lower recurrence rates.
In addition to these main data found on the minimum length
of the excised canal, we found a direct relationship between HIV
and margin impairment (6.67 and 5.99 times, respectively) and re-
currence rate, demonstrating the credibility of the data presented
in agreement with the literature regarding these factors (HIV and
margins impairment) and relapse rates.
Within the same reasoning, it could be inferred that in
manufacturing the handles used in these procedures, it ideally
could be calibrated for confection higher than 1.25 cm in relation
to their height.
At this time, after data analysis, the study concluded that:
1. The excised canal length is directly related to the relapse rates;
2. An excised canal length of 1.25 cm or longer was associated
with a lower recurrence rate;
3. Human immunodeficiency virus and compromised mar-
gins presented with 6.67 and 5.99 times higher chance of
recurrence, respectively.
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