Analysis of clinicopathological features of human papilloma virus-associated oropharyngeal squamous cell carcinoma

doi:10.19401/j.cnki.1007-3639.2022.01.006

Abstract

Abstract:

Background and purpose: Human papilloma virus-associated oropharyngeal squamous cell carcinoma (OPSCC-HPV) is a distinct entity with a significantly increasing incidence. This study aimed to observe the clinicopathological features of OPSCC-HPV. Methods: The clinical characteristics, histological morphology and immunohistochemical phenotypes of 64 cases of OPSCC-HPV who were diagnosed in Fudan University Shanghai Cancer Center from October 2013 to July 2019 were analyzed. The status of HPV and Epstein-Barr virus (EBV) in tumor tissue was detected respectively by polymerase chain reaction (PCR) and in situ hybridization. Results: There were 50 male and 14 female patients, with the age at presentation ranging from 33 to 76 years. The tonsil was the most frequently involved site, followed by the oropharyngeal wall and the base of tongue. A total of 36 patients presented with a progressively enlarged neck mass as an initial symptom, and 57 patients had cervical lymph node metastases (30 with cystic changes). The overall TNM clinical staging of American Joint Committee on Cancer (AJCC) were obtained in 55 cases. Compared to the 7th edition staging rules, the 8th edition overall clinical staging was significantly degraded. Fifty-two cases and 3 cases were diagnosed as stage Ⅰ-Ⅱ and Ⅲ, respectively. Proportion of stage Ⅰ-Ⅱ disease increased by 85.4%, and stage Ⅲ and Ⅳ diseases reduced by 52.7% and 32.7%, respectively. The consistency rate of the 7th and 8th edition clinical TNM staging was only 3.6% (2/55). During the follow-up time ranging from 2 months to 77 months, 2 patients developed local recurrence, 6 patients had cervical lymph node metastasis and 3 patients died. Sixty-three cases were non-keratinizing squamous cell carcinoma (SCC) and 1 case was adenosquamous carcinoma. Tumor cells displayed a high nuclear/cytoplasmic ratio and increased mitotic activity. Immunohistochemical staining showed that P16 was diffusely and strongly positive in 59 of 60 tested cases, and Ki-67 proliferation index was high in 24 cases. High-risk virus infection was found in all 39 patients with HPV-16 type accounting for 92.3%. A total of 35 patients underwent P16 and HPV tests simultaneously with a consistency of 97.1%. Conclusion: OPSCC-HPV has unique clinicopathological features. P16 or HPV detection should be performed on all primary OPSSC and cervical lymph node metastasis of unknown primary.

Key words: Human papilloma virus-associated oropharyngeal squamous cell carcinoma, P16, Diagnosis

CLC Number:

R739.63

ZHANG Yan, CHEN Tongzhen, ZHU Xiaoli, LI Xiaoqiu. Analysis of clinicopathological features of human papilloma virus-associated oropharyngeal squamous cell carcinoma[J]. China Oncology, 2022, 32(1): 47-53.

Figures/Tables 3

Tab. 1

Fig. 1

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References 24

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Variable	Case n (%)	Variable	Case n (%)
Age at diagnosis/year		Yes	33 (51.6)
≤60	40 (62.5)	Local recurrence
>60	24 (37.5)	No	60 (93.8)
Gender		Yes	2 (3.1)
Male	50 (78.1)	NA	2 (3.1)
Female	14 (21.9)	Follow-up
Location		Alive	61 (95.3)
Tonsil	44 (68.8)	Dead	3 (4.7)
Base of tongue	4 (6.3)	T stage
Other oropharynx	9 (14.1)	T₀	6 (9.4)
All of the above	7 (10.9)	T₁	14 (21.9)
Nodal metastases		T₂	33 (51.6)
No	5 (7.8)	T₃	4 (6.3)
Yes	57 (89.1)	T₄	2 (3.1)
NA	2 (3.1)	NA	5 (7.8)
Side of nodal metastases
Left	25 (43.9)	AJCC-8 N stage
Right	32 (56.1)	N₀	5 (7.8)
Cystic changes of nodal metastases		N₁	52 (81.3)
No	18 (31.6)	N₂	0 (0.0)
Yes	30 (52.6)	N₃	1 (1.6)
NA	9 (15.8)	NA	6 (9.4)
Tobacco/alcohol use		AJCC-7 N stage
No	19 (29.7)	N₀	5 (7.8)
Yes	40 (62.5)	N₁	36 (56.3)
NA	5 (7.8)	N₂	16 (25.0)
Oral sex		N₃	1 (1.6)
No	23 (35.9)	NA	6 (9.4)
Yes	23 (35.9)	AJCC-8 overall stage
NA	18 (28.1)	Ⅰ	48 (75.0)
Second primary malignancy		Ⅱ	4 (6.3)
No	55 (85.9)	Ⅲ	3 (4.7)
Yes	6 (9.4)	Ⅳ	0 (0.0)
NA	3 (4.7)	NA	9 (14.1)
Initial symptom		AJCC-7 overall stage
Neck mass	36 (56.3)	Ⅰ	2 (3.1)
Pharynx discomfort	18 (28.1)	Ⅱ	3 (4.7)
Both	2 (3.1)	Ⅲ	32 (50.0)
Other	4 (6.3)	Ⅳ	18 (28.1)
NA	4 (6.3)	Ki-67/%
P16 immunostaining		<60	4 (6.3)
Negative	1 (1.6)	≥60	24 (37.5)
Positive	59 (92.2)	HPV status
NA	4 (6.3)	Negative	0 (0.0)
Desmoplastic stromal reaction		Positive	39 (60.9)
No	48 (75.0)	NA	25 (39.1)
Yes	16 (25.0)	Tumor-infiltrating lymphocytes
Necrosis		No	19 (29.7)
No	31 (48.4)	Yes	45 (70.3)

Clinical stage	Ⅰ (AJCC-8)	Ⅱ (AJCC-8)	Ⅲ (AJCC-8)	Total
Ⅰ (AJCC-7)	2 (3.6)	0 (0.0)	0 (0.0)	2 (3.6)
Ⅱ (AJCC-7)	3 (5.5)	0 (0.0)	0 (0.0)	3 (5.5)
Ⅲ (AJCC-7)	29 (52.7)	3 (5.5)	0 (0.0)	32 (58.2)
Ⅳ (AJCC-7)	14 (25.4)	1 (1.8)	3 (5.5)	18 (32.7)
Total	48 (87.2)	4 (7.3)	3 (5.5)	55 (100.0)