World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 15, Number 1, February 2024, pages 90-99

Multicentricity and the Risk of Recurrence/Persistence After Laser Vaporization for High-Grade Vulvar and Vaginal Intraepithelial Neoplasia

Figure 1. Kaplan-Meier life table analysis of recurrence-free survival in high-grade VIN/VAIN patients following laser vaporization. VIN: vulvar intraepithelial neoplasia; VAIN: vaginal intraepithelial neoplasia.

Figure 2. Kaplan-Meier life table analysis of recurrence-free survival in high-grade VIN/VAIN patients following laser vaporization, comparing patients with multicentricity and patients with unicentricity (log-rank P = 0.00035). HR: hazard ratio; CI: confidence interval; VIN: vulvar intraepithelial neoplasia; VAIN: vaginal intraepithelial neoplasia.

Figure 3. Kaplan-Meier life table analysis of recurrence-free survival in high-grade VIN/VAIN patients following laser vaporization, comparing patients with multicentric intraepithelial neoplasia with unicentric intraepithelial neoplasia (log-rank P = 0.143). VIN: vulvar intraepithelial neoplasia; VAIN: vaginal intraepithelial neoplasia.

**Table 1.** Patient Characteristics
Characteristic	N (%)
^aTwo patients were diagnosed with high-grade VAIN and high-grade VIN at different times. ^bPrevious or concurrent high-grade IN of the lower genital tract. ^cHigh-grade IN or worse occurring synchronously or sequentially. ^dAny grade. ^eCombination therapy was defined as laser plus additional treatment(s). Anti-HIV: antibody to human immune deficiency virus; LSIL: low-grade squamous intraepithelial lesion; ASC-H: atypical squamous cells, high-grade squamous intraepithelial lesion cannot be excluded; ASC-US: atypical squamous cells of undetermined significance; VAIN: vaginal intraepithelial neoplasia; VIN: vulvar intraepithelial neoplasia; VAIN2: vaginal intraepithelial neoplasia grade 2; VAIN3: vaginal intraepithelial neoplasia grade 3; VIN2: vulvar intraepithelial neoplasia grade 2; VIN3: vulvar intraepithelial neoplasia grade 3; SD: standard deviation; IN: intraepithelial neoplasia.
Number of patients/number of laser-treated cases^a	63/65
Age at diagnosis: mean ± SD (range)	47.6 ± 12.2 (23 - 74)
Parity: median (range)	2 (0 - 8)
Smoking	1 (1.5)
Menopause	41 (63.0)
Positive anti-HIV test	9 (13.8)
Presenting symptoms
Mass/lesion/rash/ulcer	13 (19.6)
Itching	2 (3.0)
Abnormal cytology as presentation	47 (72.3)
LSIL/ASC-US	10 (15.3)
HSIL/ASC-H	33 (50.7)
Squamous cell carcinoma	4 (6.1)
Previous or concurrent neoplasia of the lower genital tract	44 (67.6)
Previous neoplasia	37 (56.9)
Concurrent neoplasia	7 (10.7)
Multicentric intraepithelial neoplasia of the lower genital tract^b	22 (33.8)
Metachronous	17 (26.1)
Synchronous	5 (7.6)
Previous or concurrent high-grade IN+ of the lower genital tract (multicentricity)^c	38 (58.4)
Metachronous	32 (49.2)
Synchronous	6 (9.23)
Previous or concurrent invasive cancer of the lower genital tract	16 (24.6)
History of pelvic radiation	9 (13.8)
History of hysterectomy	38 (58.4)
Concurrent VAIN/VIN^d	10 (15.3)
Concurrent high-grade VAIN/VIN	5 (7.6)
Multiple lesions	22 (33.8)
Number of lesions: median (range)	1 (1 - 6)
Final histopathologic diagnosis
VAIN2	7 (10.7)
VAIN3	44 (67.6)
VIN2	4 (6.1)
VIN3	15 (23.0)
Line of therapy
Laser as first-line therapy	59 (90.7)
Laser for recurrence after non-laser therapy	6 (9.2)
No previous laser therapy	56 (86.1)
Monotherapy or combination therapy
Laser as monotherapy	58 (89.2)
Laser as part of combination therapy^e	7 (10.7)

Table 1. Patient Characteristics

Characteristic

N (%)

^aTwo patients were diagnosed with high-grade VAIN and high-grade VIN at different times. ^bPrevious or concurrent high-grade IN of the lower genital tract. ^cHigh-grade IN or worse occurring synchronously or sequentially. ^dAny grade. ^eCombination therapy was defined as laser plus additional treatment(s). Anti-HIV: antibody to human immune deficiency virus; LSIL: low-grade squamous intraepithelial lesion; ASC-H: atypical squamous cells, high-grade squamous intraepithelial lesion cannot be excluded; ASC-US: atypical squamous cells of undetermined significance; VAIN: vaginal intraepithelial neoplasia; VIN: vulvar intraepithelial neoplasia; VAIN2: vaginal intraepithelial neoplasia grade 2; VAIN3: vaginal intraepithelial neoplasia grade 3; VIN2: vulvar intraepithelial neoplasia grade 2; VIN3: vulvar intraepithelial neoplasia grade 3; SD: standard deviation; IN: intraepithelial neoplasia.

Number of patients/number of laser-treated cases^a

63/65

Age at diagnosis: mean ± SD (range)

47.6 ± 12.2 (23 - 74)

Parity: median (range)

2 (0 - 8)

Smoking

1 (1.5)

Menopause

41 (63.0)

Positive anti-HIV test

9 (13.8)

Presenting symptoms

Mass/lesion/rash/ulcer

13 (19.6)

Itching

2 (3.0)

Abnormal cytology as presentation

47 (72.3)

LSIL/ASC-US

10 (15.3)

HSIL/ASC-H

33 (50.7)

Squamous cell carcinoma

4 (6.1)

Previous or concurrent neoplasia of the lower genital tract

44 (67.6)

Previous neoplasia

37 (56.9)

Concurrent neoplasia

7 (10.7)

Multicentric intraepithelial neoplasia of the lower genital tract^b

22 (33.8)

Metachronous

17 (26.1)

Synchronous

5 (7.6)

Previous or concurrent high-grade IN+ of the lower genital tract (multicentricity)^c

38 (58.4)

Metachronous

32 (49.2)

Synchronous

6 (9.23)

Previous or concurrent invasive cancer of the lower genital tract

16 (24.6)

History of pelvic radiation

9 (13.8)

History of hysterectomy

38 (58.4)

Concurrent VAIN/VIN^d

10 (15.3)

Concurrent high-grade VAIN/VIN

5 (7.6)

Multiple lesions

22 (33.8)

Number of lesions: median (range)

1 (1 - 6)

Final histopathologic diagnosis

VAIN2

7 (10.7)

VAIN3

44 (67.6)

VIN2

4 (6.1)

VIN3

15 (23.0)

Line of therapy

Laser as first-line therapy

59 (90.7)

Laser for recurrence after non-laser therapy

6 (9.2)

No previous laser therapy

56 (86.1)

Monotherapy or combination therapy

Laser as monotherapy

58 (89.2)

Laser as part of combination therapy^e

7 (10.7)

**Table 2.** Recurrence-Free Survival (RFS) Rates in Patients Treated With Laser Vaporization
RFS time	RFS rate (%)	95% CI
CI: confidence interval.
6 months	80.1	69.9 - 90.2
1 year	65.3	52.9 - 77.6
2 years	52.4	38.0 - 66.7
3 years	46.2	31.3 - 61.0
5 years	41.6	25.7 - 57.4

Table 2. Recurrence-Free Survival (RFS) Rates in Patients Treated With Laser Vaporization

RFS time

RFS rate (%)

95% CI

CI: confidence interval.

6 months

80.1

69.9 - 90.2

1 year

65.3

52.9 - 77.6

2 years

52.4

38.0 - 66.7

3 years

46.2

31.3 - 61.0

5 years

41.6

25.7 - 57.4

Table 3. Risk Factors for High-Grade VAIN/VIN Recurrence/Persistence

Factor

Number of cases of recurrence or persistence/total number of cases (%)

Univariate

Multivariate

95% CI

P value

95% CI

P value

^at-test. ^bFisher’s exact test. ^cPrevious or concurrent high-grade IN of the lower genital tract. ^dHigh-grade IN or worse occurring synchronously or sequentially. ^eIn the case of multicentricity, the final diagnosis was based on the disease that was most severe. ^fRecurrence after non-laser therapy. Anti-HIV: antibody to human immune deficiency virus; IN2: intraepithelial neoplasia grade 2; IN3: intraepithelial neoplasia grade 3; VAIN: vaginal intraepithelial neoplasia; VIN: vulvar intraepithelial neoplasia.

Age

0.66^a

Smoking

Yes

0/1 (0)

1.00^b

22/49 (44.9)

Menopause

Yes

21/41 (51.2)

2.10

0.73, 5.98

0.16

8/24 (33.3)

Anti-HIV test

Reactive

5/9 (55.6)

1.66

0.40, 6.87

0.49^b

Non-reactive

24/56 (42.9)

Previous or concurrent neoplasia of lower genital tract

Yes

24/44 (54.5)

3.84

1.19, 12.32

0.02

5/21 (23.8)

Multicentric intraepithelial neoplasia of lower genital tract^c

Yes

11/22 (50)

1.33

0.47, 3.75

0.58

18/42 (42.8)

Time to occur

Metachronous

10/17 (58.8)

5.71

0.52, 62.65

0.31^b

Synchronous

1/5 (20.0)

Previous or concurrent high-grade IN+ of lower genital tract (multicentricity)^d

Yes

23/38 (60.5)

5.11

1.66, 15.67

0.003

4.16

1.56, 11.06

0.004

6/26 (23.1)

Time to occur

Metachronous

21/32 (65.6)

3.81

0.60, 24.22

0.18^b

Synchronous

2/6 (33.3)

Previous or concurrent invasive cancer of lower genital tract

Yes

12/16 (75.0)

5.47

1.52, 19.61

0.009

17/48 (35.4)

History of pelvic radiation

Yes

8/9 (88.9)

13.33

1.55, 114.24

0.008^b

6.33

2.39, 16.72

0.000

21/56 (37.5)

Concurrent VAIN/VIN

Yes

5/10 (50.0)

1.29

0.33, 4.97

0.74^b

24/55 (43.6)

Multiple lesions

Yes

10/22 (45.5)

1.01

0.33, 3.03

0.98

14/31 (45.2)

Final histologic diagnosis^e

IN3

26/56 (46.4)

1.73

0.39, 7.63

0.72^b

IN2

3/9 (33.3)

Line of therapy

Laser for recurrence^f

6/6 (100.0)

2.56

1.86, 3.53

0.006^b

5.34

2.00, 14.22

0.001

Laser as first-line therapy

23/59 (39.0)

Monotherapy or combination therapy

Laser as monotherapy

25/58 (43.1)

0.56

0.11, 2.77

0.69^b

Laser as part of combination therapy

4/7 (57.1)