Cervical squamous intraepithelial lesions grades 1 and 2: value of an alternative morphological classification and of p16 immunohistochemistry in the prediction of clinical outcome

Salim, Rafael C.; Lima, Tatiana M.; Heinke, Thais; Prigenzi, Karla C. K.; Speck, Neila Maria G.; Focchi, Gustavo R. A.

doi:10.5935/1676-2444.20170050

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PATHOLOGY, Original article • J. Bras. Patol. Med. Lab. 53 (5) • Sep-Oct 2017 • https://doi.org/10.5935/1676-2444.20170050 copy

Cervical squamous intraepithelial lesions grades 1 and 2: value of an alternative morphological classification and of p16 immunohistochemistry in the prediction of clinical outcome

Lesões intraepiteliais escamosas cervicais graus 1 e 2: valor de uma classificação morfológica alternativa e do estudo imuno-histoquímico com p16 na predição do desfecho clínico

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Introduction:

Diagnostic reproducibility and determination of prognostic factors in cervical intraepithelial neoplasias grades 1 and 2 are still relevant problems in the daily practice of gynecological histopathology.

Objective:

To correlate the value of morphological reclassification and of p16 immunoexpression in cervical intraepithelial neoplasias grades 1 and 2 with clinical outcome.

Materials and methods:

Sixty-six patients were included (34 with cervical intraepithelial neoplasia grade 1, and 32 with grade 2); an immunohistochemical study with p16 and reclassification according to the Lower Anogenital Squamous Terminology (LAST) Consensus and by the alternative proposal of Herfs and Crum were done; unfavorable outcome was defined as a subsequent histologic diagnosis of cervical intraepithelial neoplasia grade 3 or invasive squamous cell carcinoma.

Results:

We observed superior performance of the alternative morphological classification (p = 0.002) to determine unfavorable outcome. We also detected superior performance of p16 in the same determination (p = 0.002).

Conclusion:

The use of an alternative morphological classification is promising; in the context of the use of immunohistochemical antibodies as biomarkers, p16 showed good sensitivity and negative predictive value in the determination of cases in which the outcome was unfavorable.

Key words:
cervical intraepithelial neoplasia; cyclin-dependent kinase inhibitor p16; outcome assessment (health care)

	n	Age (mean ± SD)	Unfavorable outcome
CIN 1	34	32.46 ± 8.47	2
CIN 2	32	32.06 ± 8.82	7
Total	66	32.27 ± 8.58	9

General frequency of p16 immunoexpression
							Positive p16
Richart's classification (n = 66)
		CIN 1						5/34
		CIN 2						21/32
		Total						26/66
Alternative classification (n = 62)
		LSIL						4/33
		QSIL						10/18
		HSIL						9/11
		Total						23/62
Specific frequency of p16 immunoexpression
		LSIL	QSIL	HSIL				Total	P
CIN 1
P16
Negative	28	90.3%	-	-	-	-	28	84.8%	0.019^a a Fisher's exact test or its extension.
Positive	3	9.7%	2	100%	-	-	5	15.2%
Total	31	100%	2	100%	-	-	33	100%
CIN 2
P16
Negative	1	50%	8	50%	2	18.2%	11	37.9%	0.195^a a Fisher's exact test or its extension.
Positive	1	50%	8	50%	9	81.8%	18	62.1%
Total	2	100%	16	100%	11	100%	29	100%

		Outcome
		Favorable	Unfavorable		Total	p-value	S	Sp
p16	Negative	39 68.4%	1 11.1%	40	60.6%	0.002^a a Fisher's exact test.	0.889	0.684
	Positive	18 31.6%	8 88.9%	26	39.4%
	Total	57 100%	9 100%	66	100%

Outcomes
	Favorable		Unfavorable		Total		p -value
Richart's classification
CIN 1	32	94.1%	2	5.9%	34	100%	0.079^a a Fisher's exact test or its extension.
CIN 2	25	78.1%	7	21.9%	32	100%
Total	57	86.4%	9	13.6%	66	100%
LAST Consensus
LSIL	41	93.2%	3	6.8%	44	100%	0.051^a a Fisher's exact test or its extension.
HSIL	16	72.7%	6	27.3%	22	100%
Total	57	86.4%	9	13.6%	66	100%
Alternative classification
LSIL	32	97%	1	3%	33	100%	0.002^a a Fisher's exact test or its extension.
QSIL	15	83.3%	3	16.7%	18	100%
HSIL	6	54.5%	5	45.5%	11	100%
Total	53	85.5%	9	14.5%	62	100%

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E-mail: jbpml@sbpc.org.br

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[1] CORRESPONDING AUTHOR: Thais Heinke, Rua Muniz de Sousa, 492, apto 81, Edifício Florae; Aclimação; CEP: 01534-001; São Paulo-SP, Brasil; e-mail: thaish1978@gmail.com.