International Journal of Clinical Oncology (2021) 26:770–776

https://doi.org/10.1007/s10147-020-01848-x

ORIGINAL ARTICLE

Prognostic outcomes and risk factors for recurrence after laser

vaporization for cervical intraepithelial neoplasia: a single‑center
retrospective study
Keisuke Kodama1 · Hideaki Yahata1   · Kaoru Okugawa1 · Hiroshi Tomonobe1 · Nobuko Yasutake1 ·
Sachiko Yoshida1 · Hiroshi Yagi1 · Masafumi Yasunaga1 · Tatsuhiro Ohgami1 · Ichiro Onoyama1 · Kazuo Asanoma1 ·
Emiko Hori1 · Mototsugu Shimokawa2 · Kiyoko Kato1

Received: 8 October 2020 / Accepted: 26 November 2020 / Published online: 4 January 2021
© Japan Society of Clinical Oncology 2021

Abstract
Background  Cervical intraepithelial neoplasia (CIN) is a precancerous lesion that may progress to invasive cervical cancer
without intervention. We aim to examine the prognostic outcomes and risk factors for recurrence after laser vaporization for
CIN 3, CIN 2 with high-risk human papillomavirus (HPV) infection, and CIN 1 persisting for more than 2 years.
Methods  Between 2008 and 2016, a total of 1070 patients underwent cervical laser vaporization using a carbon dioxide
laser. We performed a retrospective review of their medical records to assess their clinical characteristics, pathologic factors,
and prognostic outcomes.
Results  The mean patient age was 34 years (range 18–64 years). The preoperative diagnosis was CIN 1 in 27 patients, CIN
2 in 485 patients, and CIN 3 in 558 patients. Over a median follow-up period of 15 months, the 2-year recurrence rate was
18.9%, and the 5-year recurrence rate was 46.5%. The 2-year retreatment rate was 12.6%, and the 5-year retreatment rate
was 30.5%. We diagnosed 9 patients with invasive cancer after treatment; all patients underwent combined multidisciplinary
treatment, and there were no deaths during follow-up. The recurrence-free interval was correlated with patient age (hazard
ratio [HR], 1.028; 95% CI 1.005–1.051; P = 0.0167), body mass index (HR, 1.052; 95% CI 1.008–1.098; P = 0.0191), and
glandular involvement (HR, 1.962; 95% CI 1.353–2.846; P = 0.0004).
Conclusions  Cervical laser vaporization is effective and useful for patients with CIN who wish to preserve fertility. However,
patients with glandular involvement, older age, and higher body weight require close follow-up for recurrence.

Keywords  Cervical intraepithelial neoplasia · Laser vaporization · Recurrence-free interval

Introduction of the uterine cervix are caused by mucosal subtypes and

Cervical intraepithelial neoplasia (CIN) is caused by certain
subtypes of the human papillomavirus (HPV). It is a pre-
cancerous lesion that can progress to cervical cancer if not
treated [1]. Currently, more than 100 subtypes are known to
cause mucosal and cutaneous infectious in humans. Lesions
* Hideaki Yahata
hyahata@med.kyushu‑u.ac.jp
1
Department of Obstetrics and Gynecology, Graduate School
of Medical Sciences, Kyushu University, 3‑1‑1 Maidashi,
Higashi‑ku, Fukuoka 812‑8582, Japan
2 3 before it progresses to invasive cancer. The recommended
Department of Biostatistics, Graduate School of Medicine,
Yamaguchi University, 1‑1‑1 Minamikogushi, Ube,
Yamaguchi 755‑8505, Japan
progress from precancerous changes to cervical cancer over
5–10 years after infection [2]. The classification of CIN
divides the disease into reversible lesions (CIN 1, CIN 2)
that can revert to normal tissue, and precancerous lesions
(CIN 3, CIN 2 with high-risk HPV infection) that may pro-
gress to invasive cancer [3]. The probability of developing
invasive cancer is 1% for patients with CIN1, 5% for those
with CIN2, and 12% for those with CIN3 [4].
In recent years, the number of young patients with inva-
sive cervical cancer has been increasing [5–7]. Treatment
often requires radical hysterectomy and radiotherapy, result-
ing in loss of fertility. Therefore, it is important to treat CIN
treatment is cone resection, which removes a cone-shaped
portion of the cervix, with the base of the cone describing

13
Vol:.(1234567890)
International Journal of Clinical Oncology (2021) 26:770–776 771
a 1- to 2-cm circle around the cervical os. Cone resection
allows for histologic examination, but postoperative cervi-
cal stenosis can cause dysmenorrhea, resection of cervical
secretory glands can cause infertility, and a shortened cervi-
cal length can lead to premature rupture of membranes and
preterm birth in future pregnancies [8].
Other treatments for CIN include cervical laser vaporiza-
tion, cryotherapy, and photodynamic therapy. Cervical laser
vaporization is effective, minimally invasive, and has a lower
rate of perinatal complications than other treatments. Its
minimal effect on fertility is useful given the current trend
toward later childbearing [9]. However, a histologic diag-
nosis is not possible after treatment, and there are reports
of invasive cancer being missed. In addition, recurrence of
CIN after laser treatment is often reported.
Because of the advantages and disadvantages of these
treatment methods, strategies for CIN need to be carefully
thought out [10]. The aim of this study is to evaluate the
prognostic outcomes in patients who undergo cervical laser
vaporization for CIN and to elucidate the risk factors for
recurrence.
Materials and methods
Patients
We retrospectively reviewed the medical records of patients
with pathologically confirmed CIN who were treated with
cervical laser vaporization between April 2008 and Decem-
ber 2016 at Kyushu University Hospital. The indications
for laser vaporization were CIN 3, CIN 2 with high-risk
HPV infection, and CIN 1 persisting for more than 2 years.
Cervical laser vaporization was performed in patients who
wished to preserve fertility and in whom the squamocolum-
nar junction was visible on colposcopy. We performed both
cervical cytology and histology before surgery; if there was a
discrepancy between cytology and histology, we performed
cervical conization. Preoperative diagnoses were confirmed
at a  weekly conference of gynecologic oncologists and
gynecologic pathologists. The treatment was performed on
an outpatient basis by gynecologic oncologists. This study
was approved by the institutional review board of Kyushu
University Hospital (No. 30–390), and written informed
consent was obtained from all patients.
Procedure
Laser vaporization was carried out under colposcopic visu-
alization, using a carbon dioxide laser (Laser 2­ 0Z®; MM
& NIIC Co. Ltd., Tokyo, Japan) with a power of 20 W in
pulsed or continuous mode. All patients received a paracer-
vical block using 1% mepivacaine hydrochloride. General
anesthesia was not employed. The squamocolumnar junction
was visualized in all patients before laser vaporization could
begin. Vaporization was performed to a depth of 8–10 mm,
with margins 5 mm away from either the abnormal finding
or the transformation zone.
Follow‑up and retreatment
All patients attended postoperative follow-up every 3 months
for the first year and every 6 months for the second year.
If any abnormal findings were detected, follow-up was
extended until the absence of abnormalities could be con-
firmed. All patients underwent cervical cytology, obtained
under colposcopic visualization, and targeted biopsy if
abnormal findings were present on colposcopy (e.g., ace-
towhite epithelium, punctuation, mosaicism) or if abnormal
findings were noted on cytology (e.g., atypical squamous
cells of undetermined significance [ASC-US], low-grade
squamous intraepithelial lesions [LSIL], high-grade squa-
mous intraepithelial lesions [HSIL], atypical squamous
cells—cannot exclude HSIL [ASC-H]). If there were no
abnormalities on colposcopy or cytology for 2 years after
treatment, patients were considered to have completed
follow-up and were advised to attend annual visits with a
primary care gynecologist.
Recurrence was defined as the detection of CIN 1 or
greater on histopathologic examination of cervical biopsy
tissue. Patients with CIN 1 after laser vaporization were
closely followed without additional treatment. Treatment
for recurrence was performed when CIN 2, CIN 3, or inva-
sive cancer was detected. Repeat laser vaporization, cervical
conization, or hysterectomy were offered to patients with
recurrent CIN, and multidisciplinary treatment was used for
patients with invasive cervical cancer. The recurrence-free
interval 1 (RFI 1) was defined as the period until diagnosis
of CIN 1 or greater, and the recurrence-free interval 2 (RFI
2) was defined as the period until diagnosis of CIN 2, CIN
3, or invasive cancer (a diagnosis requiring retreatment).
Analysis
We obtained data on patient age, body mass index (BMI),
parity, preoperative diagnosis, HPV infection status, glandu-
lar involvement, and postoperative invasive cancer from the
medical records, and descriptive statistics were applied. The
RFI 1 and RFI 2 were determined using the Kaplan–Meier
method. Kaplan–Meier curves and risk factors were ana-
lyzed using the Cox proportional hazards model (univariate
analysis and multivariate analysis). All statistical analyses
were performed using SAS software, version 9.4 (SAS Insti-
tute, Cary, NC). Statistical significance was defined at a P
value of less than 0.05.
13

772 International Journal of Clinical Oncology (2021) 26:770–776

Results Table 1  Patient characteristics (n = 1070)

Age (range), years 34 (18–64)

Patient characteristics BMI (range), kg/m2 20.3 (15.1–51.1)
Gravidity, n (%)
A total of 1070 patients underwent cervical laser vapori-  0 323 (30.2)
zation. No patients had undergone previous conization or  ≥ 1 747 (69.8)
laser vaporization. The median patient age was 34 years Parity, n (%)
(range 18–64 years). The median BMI was 20.3 kg/m2  0 448 (41.9)
(range 15.1–51.1 kg/m2). A total of 323 patients (30.2%)  ≥ 1 622 (58.1)
were nulligravid, and 448 were nulliparous. The preopera- Diagnosis, n (%)
tive diagnosis was CIN 1 in 27 patients (2.5%), CIN 2 in  CIN 1 27 (2.5)
485 patients (45.4%), and CIN 3 in 558 patients (52.1%).  CIN 2 485 (45.4)
Because HPV typing in patients with CIN 3 has not  CIN 3 558 (52.1)
been adopted by Japan National Health Insurance, HPV HPV infection, n (%)
testing was not performed in 589 patients (55%). A total of  Not examined 589 (55.0)
463 patients (43.3%) had HPV infection detected, and 18  Positive 463 (43.3)
patients (1.7%) had no HPV infection. Glandular involve-  Negative 18 (1.7)
ment was recognized in 639 patients (59.7%). Glandular involvement, n (%)
Perioperative complications were few: local infec-  Positive 639 (59.7)
tion occurred in 5 patients and postoperative bleeding  Negative 431 (40.3)
in 33 patients. A total of 22 patients were taking immu- Perioperative complications, n (%)
nosuppressant medication for autoimmune disease or  Local infection* 5 (0.5)
organ transplantation. The median follow-up period was  Bleeding* 33 (3.1)
15 months (range 0–131 months). The 2-year recurrence Immunosuppression** 22 (2.0)
rate was 18.9%, and the 2-year retreatment rate was 12.6% Follow-up (range), months 15 (0–131)
(Table 1). For patients with recurrence, the surgical proce- Recurrence, n (%) 202 (18.9)
dure was determined according to the individual features Recurrence requiring treatment, n (%) 139 (13.0)
of the case. Repeat cervical laser vaporization was per- Recurrence as invasive cancer, n (%) 9 (0.8)
formed when the squamocolumnar junction was visible on
colposcopy. Cervical conization was performed when the BMI body mass index, CIN cervical intraepithelial neoplasia, HPV
human papillomavirus
squamocolumnar junction was not visible on colposcopy
*Clavein-Dindo classification grade 2 or less
and when invasive cancer could not be ruled out. Either
simple, modified radical, or radical hysterectomy was per- **Transplantation, autoimmune disease
formed in patients diagnosed with invasive cancer.
involvement (HR, 1.812; 95% CI 1.257–2.613; P = 0.0014)
were significantly correlated with recurrence. The degree
Recurrence‑free interval of CIN did not affect the RFI. Multivariate analysis
showed a persistent effect of patient age (HR, 1.028; 95%
If there were no abnormalities on colposcopy or cytol- CI 1.005–1.051; P = 0.0167), BMI (HR, 1.052; 95% CI
ogy for 2 years after treatment, patients were considered 1.008–1.098; P = 0.0191), and glandular involvement (HR,
to have completed follow-up and were advised to attend 1.962; 95% CI 1.353–2.846; P = 0.0004).
annual visits with a primary care gynecologist. Therefore,
we decided to calculate the 2-year recurrence-free inter- Invasive cervical cancer
val. Figure 1 shows the Kaplan–Meier curves for RFI 1
and RFI 2. The 2-year RFI 1 rate was 78.5% (95% CI A total of 9 patients (0.8%) developed invasive cancer after
75.1–81.5%), and the 2-year RFI 2 rate was 85.3% (95% laser vaporization. The therapeutic options used, outcomes
CI 82.3–87.9%). Table 2 shows the results of univariate achieved, and clinicopathologic variables are listed in
and multivariate analysis of RFI according to patient age, Table 3. Of these 9 patients, 8 had an original diagnosis of
BMI, glandular involvement, complications, and CIN clas- CIN 3, and 1 had CIN 2. The FIGO (International Federation
sification. On univariate analysis, patient age (hazard ratio of Gynecology and Obstetrics) stage was IA1 in 1 patient,
[HR], 1.023; 95% CI 1.001–1.046; P = 0.0413), BMI (HR, IA2 in 2 patients, IB1 in 4 patients, IB2 in 1 patient, and IVB
1.051; 95% CI 1.008–1.095; P = 0.0197), and glandular in 1 patient. Four of the 9 patients experienced endocervical
recurrence, and 5 experienced ectocervical recurrence. All

13
International Journal of Clinical Oncology (2021) 26:770–776 773

Fig. 1  Recurrence-Free Interval
1.0
(RFI). Dotted line: time to
diagnosis of recurrence of any 0.9
cervical intraepithelial neoplasia

Recurrent-free interval rate

(RFI 1). Solid line: time to diag- 0.8
nosis of recurrence of cervical 0.7
intraepithelial neoplasia requir-
ing retreatment (RFI 2) 0.6
0.5
0.4
0.3
0.2
0.1
0.0
0 1 2 3 4 5
Years
No. at risk
RFI1 1070 683 206 85 46 23
RFI2 1070 741 249 113 61 33

Table 2  Recurrence of CIN Univariate Multivariate

requiring retreatment (Cox
proportional hazards model) HR (95% CI) P value HR (95% CI) P value

Age 1.023 (1.001–1.046) 0.0413 1.028 (1.005–1.051) 0.0167

BMI 1.051 (1.008–1.095) 0.0197 1.052 (1.008–1.098) 0.0191
CIN 2 vs CIN 1 0.680 (0.290–1.591) 0.3734
CIN 3 vs CIN 1 1.017 (0.441–2.343) 0.9688
Complications 1.327 (0.543–3.245) 0.5352
Glandular involvement 1.812 (1.25–2.613) 0.0014 1.962 (1.353–2.846) 0.0004

BMI body mass index, CIN cervical intraepithelial neoplasia, HR hazard ratio

patients with endocervical recurrence had a tumor diameter
over 3 cm. One patient with stage IVB disease was diag-
nosed with recurrence 4 years after laser treatment. She
originally completed 2 years of follow-up at our hospital
without any evidence of disease, but she then neglected to
undergo further follow-up for cervical cytology. She visited
another hospital with edema of the left lower extremity and
was referred to us when a uterine tumor was noted. This
tumor consisted of nonkeratinizing squamous cell carcinoma
on cytology and histology. Computed tomography revealed
swelling of the left pelvic lymph nodes, para-aortic lymph
nodes, and left subclavian lymph nodes. Magnetic resonance
imaging revealed a 5-cm endophytic tumor in the endocer-
vix. She received chemotherapy followed by concurrent
chemoradiation. Two cases were diagnosed within 9 months
after laser vaporization. All patients received multidiscipli-
nary treatment including hysterectomy, tumor resection,
concurrent chemoradiation, and chemotherapy. One patient
with stage IA1 disease, 2 with stage IA2 disease, and 4 with
stage IB1 disease were alive with no evidence of disease
at the time of final follow-up. One patient with stage IB2
disease and the previously described patient with stage IVB
disease were alive with disease.
Discussion
There are many prospective and retrospective studies of laser
vaporization for CIN, beginning in the 1980s [11–15]. Laser
vaporization is considered useful because of its outpatient
nature and low rate of perinatal complications (e.g., preterm
delivery, low birthweight, cesarean delivery, perinatal mor-
tality). Laser therapy has fewer perioperative complications
than conization and is a useful treatment for young patients
who wish to preserve fertility [8, 9]. In our study population
of relatively young patients and many nulliparous patients,
laser therapy is a valid choice for treatment.
Treatment outcomes are extremely important when
choosing a treatment modality. Our data show that the recur-
rence rate is 18.9% and the retreatment rate is 12.6% after
laser vaporization, with an RFI 1 of 78.5% and an RFI 2
of 85.3%. Mariya et al. report a remission rate of 89.7% at

13

774

13
Table 3  Recurrence as invasive cancer
Age (years) BMI Diagnosis HPV subtype Glandular Pathology Location of Stage Tumor size Treatment **Treat- Outcome
(kg/m2) involve- recurrent ment period
ment tumor (months)

1 34 20.6 CIN 3 *  +  SCC Ectocervical IA2 4.5 mm deep, 5 mm mRAH 8 NED
wide
2 43 18.9 CIN 3 *  +  SCC Endocervical IVB 5 cm TC + Bev × 10, 56 AWD
CDDP + CPT-11 × 6,
CCRT, Etoposide × 3
3 27 17.8 CIN 3 16  +  ***Adenocarcinoma Ectocervical IB1 1 cm RAH →  32 NED
CDDP + CPT-11 × 6
4 28 20.8 CIN 3 *  +  SCC Ectocervical IA2 3.5 mm deep, 6 mm mRAT​ 57 NED
wide
5 39 27.2 CIN 3 *  +  SCC Endocervical IB1 3.5 cm RAH → CCRT​ 47 NED
6 35 21.6 CIN 3 18  +  SCC Ectocervical IB1 2 cm RAH + TC × 6 21 NED
7 34 19.6 CIN 3 *  +  SCC Endocervical IB1 3 cm LRH → CCRT​ 29 NED
8 47 18.2 CIN 2 *  +  SCC Ectocervical IA1 1 mm deep, 1 mm wide TAH + BSO 13 NED
9 43 22.4 CIN 3 *  +  SCC Endocervical IB2 5 cm CCRT, TC + Bev × 7, 9 AWD
tumor resection,
CCRT, TC + Bev × 4,
CDDP + CPT-11 × 6

BMI body mass index, CIN cervical intraepithelial neoplasia, HPV human papillomavirus, SCC squamous cell carcinoma, NED no evidence of disease, AWD alive with disease, TC pacli-
taxel plus carboplatin, CDDP + CPT-11 cisplatin plus irinotecan, Bev bevacizumab, CCRT​ concurrent chemoradiotherapy, BSO bilateral salpingo-oophorectomy, LRH laparoscopic radical hys-
terectomy, mRAH modified radical abdominal hysterectomy, mRAT​modified radical abdominal trachelectomy, RAH radical abdominal hysterectomy, TAH total abdominal hysterectomy
*Not tested
**Time required for radical treatment after laser vaporization
***Adenocarcinoma with small cell carcinoma
International Journal of Clinical Oncology (2021) 26:770–776
International Journal of Clinical Oncology (2021) 26:770–776 775
5 months after laser treatment [16], and Inaba et al. report a
recurrence-free rate of 77.4% at 12 months after laser ther-
apy [17]. Our outcomes are the same as those of these previ-
ous reports. It is important to keep in mind that about 10% to
20% of patients experience a recurrence after laser therapy,
so postoperative follow-up, including cervical cytology and
colposcopic examination, is important.
In our study, 9 patients developed invasive cervical cancer
after laser vaporization, an incidence that is the same as that
reported by Stentella et al. who found that the cumulative
rate of invasive cancer 8 years after treatment is 8.9 per 1000
women [18]. Soutter et al. report the cumulative rate of inva-
sive cancer 4 and 8 years after treatment is 2.9 and 4.6 per
1000 women, respectively [19, 20]. We previously found a
cumulative rate of invasive cancer 10 years after treatment of
8.4 per 1000 women [21, 22]. In the present study, 2 women
developed invasive cancer within 9 months of laser therapy.
It is generally thought that CIN 2 and CIN 3 require several
years to progress to cervical cancer [6]. Given this short
interval, our 2 patients might already have had cervical can-
cer at the time of laser treatment. The other 7 patients with
invasive cervical cancer were diagnosed between 13 and
56 months after laser vaporization. All had normal cervical
cytology and colposcopic findings after laser therapy. We
must assume, therefore, that their CIN lesions were cured
temporarily, and their cervical cancer appeared later. Fortu-
nately, the use of multidisciplinary treatment allowed all 9
patients to survive.
To minimize the number of patients experiencing invasive
cancer after treatment of CIN, treatment decisions should
be carefully made. Conization should be chosen for patients
with a discrepancy between the colposcopic findings and
the cytologic and histologic findings, so that a definitive
diagnosis can be made. Follow-up may also need modifi-
cation. Because five of our patients with invasive cancer
had a mass measuring greater than 2 cm at the intracervical
canal, adding transvaginal ultrasonography to the follow-up
examination that currently includes bimanual examination,
colposcopic examination, and cervical cytology could be
considered.
Our results demonstrate that glandular involvement is
a risk factor for recurrence of CIN after laser therapy. At
our center, we always check for glandular involvement on
biopsy specimens at the preoperative gynecologic oncol-
ogy–pathology conference. A retrospective study of 77
patients who underwent cold knife conization and 139
who underwent loop electrosurgical excisional proce-
dures found that glandular involvement is seen in 80.8%
of specimens with positive margins, while recurrence
occurs in 18.2% of patients with positive margins but no
glandular involvement (P < 0.001) [23]. In patients with
glandular involvement, the CIN lesion may be hidden deep
to the surface of the uterine cervix. Because glandular
involvement is a significant risk factor for recurrence, we
recommend that laser vaporization should be performed
more widely and deeply to prevent recurrence in patients
with this pathologic finding.
We also found that older age is a risk factor for recurrence
of CIN after laser therapy. Patients older than 40 years of age
have a risk for recurrence 1.75 times greater than younger
patients (95% CI 1.12–2.74) [24]. Older patients might be
infected with HPV for a longer period of time than younger
patients; if this is the case, older patients may be more likely
to experience recurrence after laser vaporization. In addi-
tion, the squamocolumnar junction typically regresses into
the cervical canal as age advances, meaning that CIN lesions
may remain hidden in the cervix after laser therapy.
Finally, we found that a higher BMI is a risk factor for
recurrence of CIN after laser therapy. There is no literature
exploring the relationship between BMI and recurrence after
laser vaporization. However, Bogani et al. report that the
complication rates in patients undergoing vaginal hyster-
ectomy increase as BMI increases (OR, 1.01 [1.00–1.02]
for a 1-unit increase in BMI; P = 0.05) and are higher than
in patients undergoing laparoscopic hysterectomy [25].
The higher recurrence rate we noted in patients with higher
body weight may be due to difficulty visualizing the field for
vaporization. We often experience difficulty with vaginal
examination due to extrusion of the vaginal side walls in
obese patients. In these patients, laser vaporization might
be better performed in the hospital with adequate anesthesia
rather than in the outpatient setting. This precaution may
help to prevent incomplete laser therapy in patients with
higher body weight.
Our study has several limitations. First, HPV typing was
not allowed by Japan National Health Insurance for patients
with CIN 3; therefore, more than half of our patients were
not tested for HPV infection. Byun et al. report 6 patients
with CIN 2 who had recurrent disease after cold knife coni-
zation or loop electrosurgical excision; all were HPV-posi-
tive after treatment, whereas all 114 patients without HPV
infection had no recurrence after treatment (P = 0.002). They
also note that patients with persistent HPV-16 infection after
treatment have a significantly higher risk for recurrence after
conization than patients with non-16 HPV infection (HR,
19.4; 95% CI 1.89–198.79; P = 0.012) [26]. We found no
association between HPV infection or HPV subtype and
recurrence after laser therapy.
Another limitation is our relatively short follow-up
period. After a median of only 15 months, the perinatal
outcomes of almost all our patients remain unclear. Mariya
et al. report that cervical cerclage was required in 3 of 14
women in their conization group, and no cerclages were
required in their vaporization group [16]. Laser vaporiza-
tion has a lower rate of perinatal complications than other
treatments [9], but longer follow-up is needed to prove the
13

776
advantage of laser therapy for young patients who desire
future fertility.
In conclusion, cervical laser vaporization for CIN is
effective and useful for patients who wish to preserve fertil-
ity. However, patients with glandular involvement, older age,
and higher body weight require close follow-up for recur-
rence. Large, prospective, randomized, multicenter studies
are required to better assess the value of various therapeutic
strategies.
Acknowledgements  This study was supported in part by a Grant-in-
Aid for Scientific Research from the Japan Society for the Promotion
of Science (Number JP19K09804).
Compliance with ethical standards  42(12):1808–1813. https​://doi.org/10.1111/jog.13113​
Conflict of interest  The authors declare that they have no conflicts of
interest.
References
1. Parkin DM, Bray F, Ferlay J et al (2002) (2005) Global cancer
statistics. CA Cancer J Clin 55(2):74–108. https:​ //doi.org/10.3322/
canjc​lin.55.2.74
2. International Agency for Research on Cancer Multicenter Cervical
Cancer Study G, Munoz N, Bosch FX, de Sanjose S et al (2003)
Epidemiologic classification of human papillomavirus types asso-
ciated with cervical cancer. N Engl J Med 348(6):518–527. https​
://doi.org/10.1056/NEJMo​a0216​41
3. Brianti P, De Flammineis E, Mercuri SR (2017) Review of HPV-
related diseases and cancers. New Microbiol 40(2):80–85
4. Ostör AG (1993) Natural history of cervical intraepithelial neo-
plasia: a critical review. Int J Gynecol Pathol 12(2):186–192
5. Ginsburg O, Bray F, Coleman MP et al (2017) The global bur-
den of women’s cancers: a grand challenge in global health. The
Lancet 389(10071):847–860. https ​ : //doi.org/10.1016/s0140​
-6736(16)31392​-7
6. Sawaya GF, Smith-McCune K, Kuppermann M (2019) Cervical
cancer screening: more choices in 2019. JAMA 321(20):2018–
2019. https​://doi.org/10.1001/jama.2019.4595
7. Kocken M, Helmerhorst TJM, Berkhof J et al (2011) Risk of
recurrent high-grade cervical intraepithelial neoplasia after suc-
cessful treatment: a long-term multi-cohort study. Lancet Oncol
12(5):441–450. https​://doi.org/10.1016/s1470​-2045(11)70078​-x
8. Sadler L, Saftlas A, Wang W et al (2004) Treatment for cervi-
cal intraepithelial neoplasia and risk of preterm delivery. JAMA
291(17):2100–2106. https​://doi.org/10.1001/jama.291.17.2100
9. Kyrgiou M, Koliopoulos G, Martin-Hirsch P et al (2006) Obstet-
ric outcomes after conservative treatment for intraepithelial or
early invasive cervical lesions: systematic review and meta-anal-
ysis. Lancet 367(9509):489–498. https​://doi.org/10.1016/s0140​
-6736(06)68181​-6
10. Mathevet P, Chemali E, Roy M et al (2003) Long-term outcome
of a randomized study comparing three techniques of conization:
cold knife, laser, and LEEP. Eur J Obstet Gynecol Reprod Biol
106(2):214–218. https:​ //doi.org/10.1016/s0301-​ 2115(02)00245-​ 2
11. Anderson MC, Hartley RB (1979) Cervical crypt involvement by
intraepithelial neoplasia. Obstet Gynecol Surv 34(11):852–853.
https​://doi.org/10.1097/00006​254-19791​1000-00031​
12. Jordan JA, Woodman CB, Mylotte MJ et  al (1985) The
treatment of cervical intraepithelial neoplasia by laser
13
International Journal of Clinical Oncology (2021) 26:770–776
vaporization. Br J Obstet Gynaecol 92(4):394–398. https​://doi.
org/10.1111/j.1471-0528.1985.tb011​14.x
13. Partington CK, Turner MJ, Soutter WP et al (1989) Laser vapori-
zation versus laser excision conization in the treatment of cervical
intraepithelial neoplasia. Obstet Gynecol 73:775–779
14. Alvarez RD, Helm CW, Edwards RP et al (1994) Prospective
randomized trial of LLETZ versus laser ablation in patients with
cervical intraepithelial neoplasia. Gynecol Oncol 52(2):175–179.
https​://doi.org/10.1006/gyno.1994.1027
15. Dey P, Gibbs A, Arnold DF et al (2002) Loop diathermy exci-
sion compared with cervical laser vaporisation for the treatment
of intraepithelial neoplasia: a randomised controlled trial. BJOG
109(4):381–385. https:​ //doi.org/10.1111/j.1471-0528.2002.01277​
.x
16. Mariya T, Nishikawa A, Sogawa K et al (2016) Virological and
cytological clearance in laser vaporization and conization for cer-
vical intra-epithelial neoplasia grade 3. J Obstet Gynaecol Res
17. Inaba K, Nagasaka K, Kawana K et al (2014) High-risk human
papillomavirus correlates with recurrence after laser ablation for
treatment of patients with cervical intraepithelial neoplasia 3: a
long-term follow-up retrospective study. J Obstet Gynaecol Res
40(2):554–560. https​://doi.org/10.1111/jog.12196​
18. Stentella P, Pace S, Villani C et al (1995) Cervical intraepithelial
neoplasia: carbon dioxide laser vaporization and conization. Our
Exp Eur J Gynaecol Oncol 16(4):282–289
19. Soutter WP, de Barros LA, Fletcher A et al (1997) Invasive cervi-
cal cancer after conservative therapy for cervical intraepithelial
neoplasia. Lancet 349(9057):978–980. https​://doi.org/10.1016/
s0140​-6736(96)08295​-5
20. Soutter WP, Sasieni P, Panoskaltsis T (2006) Long-term risk of
invasive cervical cancer after treatment of squamous cervical
intraepithelial neoplasia. Int J Cancer 118(8):2048–2055. https​://
doi.org/10.1002/ijc.21604​
21. Chew GK, Jandial L, Paraskevaidis E et al (1999) Pattern of CIN
recurrence following laser ablation treatment: long-term follow-
up. Int J Gynecol Cancer 9(6):487–490. https​://doi.org/10.104
6/j.1525-1438.1999.99066​.x
22. Persad VL, Pierotic MA, Guijon FB (2001) Management of
cervical neoplasia: a 13-year experience with cryotherapy and
laser. J Low Genit Tract Dis 5(4):199–203. https​://doi.org/10.10
46/j.1526-0976.2001.54002​.x
23. Chen JY, Wang ZL, Wang ZY et  al (2018) The risk factors
of residual lesions and recurrence of the high-grade cervical
intraepithelial lesions (HSIL) patients with positive-margin after
conization. Medicine (Baltimore) 97(41):e12792. https​://doi.
org/10.1097/MD.00000​00000​01279​2
24. Melnikow J, McGahan C, Sawaya GF et  al (2009) Cervical
intraepithelial neoplasia outcomes after treatment: long-term fol-
low-up from the British Columbia Cohort Study. J Natl Cancer
Inst 101(10):721–728. https​://doi.org/10.1093/jnci/djp08​9
25. Bogani G, Cromi A, Serati M et al (2015) Laparoscopic and
vaginal approaches to hysterectomy in the obese. Eur J Obstet
Gynecol Reprod Biol 189:85–90. https​://doi.org/10.1016/j.ejogr​
b.2015.02.035
26. Byun JM, Jeong DH, Kim YN et al (2018) Persistent HPV-16
infection leads to recurrence of high-grade cervical intraepithe-
lial neoplasia. Medicine (Baltimore) 97(51):e13606. https​://doi.
org/10.1097/MD.00000​00000​01360​6
Publisher’s Note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.