Tran D N L, Vo H N, Cung T T A, Tran N D, Cao H N
Department of Oncology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam.
International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Cancer Med. 2025 Jun;14(11):e70982. doi: 10.1002/cam4.70982.
Vulvar cancer (VC) is rare; however, its incidence has steadily increased, likely due to increased human papillomavirus (HPV) infections. HPV infection rates vary significantly with age and ethnicity. Data on the VC incidence in Vietnam are limited.
This study aimed to determine HPV infection rates and high-risk HPV types (HR-HPVs) and to model HPV causality in co-infections using a Proportional Attribution (PropAttr) model in Vietnamese VC patients.
We investigated primary VC cases (invasive carcinoma) diagnosed at our hospital during 2020-2021. Tumor samples were tested for HPV using quantitative polymerase chain reaction. Recurrent cases and poor-quality preserved tumor samples were excluded. HPV infection status, HR-HPV status, and relevant clinicopathological features were analyzed. To estimate the most likely causative HPV genotype in co-infected lesions, the PropAttr model was applied, attributing genotypes based on their prevalence in mono-infections. Model reliability was validated using Spearman's correlation analysis.
Of the 95 cases, 95% were squamous cell carcinoma, and 40% were clinical stage I. The HPV infection rate was approximately 77% (68.4-85.2), and HPV-16 was the most common subtype. Patients infected with HPV (mean age: 62.8) were younger than those who were not infected (mean age: 71.4) in univariate (p = 0.004) and multivariate (p < 0.001) analyses. While the vulvar pathohistological type was significantly associated with HPV infection in multivariate analysis (p < 0.001), no significant relationship was observed with other factors in univariate and multivariate analyses. The PropAttr model showed significant correlations between attribution estimates and mono-infection prevalence (HPV-16: ρ = 0.806, p < 0.001; HPV-18: ρ = 0.992, p < 0.001; 12 other HR-HPVs: ρ = 0.880, p < 0.001). A strong negative correlation between HPV-16 and 12 other HR-HPVs (ρ = -0.751, p < 0.001) suggested competitive interactions in genotype assignment.
The HPV infection rate in Vietnamese VC cases was substantially higher than in other Asian populations, indicating a significant public health burden. Our findings reinforce the importance of expanding national HPV vaccination programs and incorporating advanced attribution models to improve HPV-related cancer risk assessment.
外阴癌（VC）较为罕见；然而，其发病率呈稳步上升趋势，这可能归因于人乳头瘤病毒（HPV）感染的增加。HPV感染率随年龄和种族的不同而有显著差异。越南关于VC发病率的数据有限。
本研究旨在确定越南VC患者中HPV感染率及高危HPV类型（HR-HPVs），并使用比例归因（PropAttr）模型对合并感染中的HPV因果关系进行建模。
我们调查了2020 - 2021年在我院诊断的原发性VC病例（浸润性癌）。采用定量聚合酶链反应对肿瘤样本进行HPV检测。排除复发病例及保存质量差的肿瘤样本。分析HPV感染状态、HR-HPV状态及相关临床病理特征。为估计合并感染病变中最可能的致病HPV基因型，应用PropAttr模型，根据其在单一感染中的流行率来确定基因型。使用Spearman相关分析验证模型的可靠性。
95例病例中，95%为鳞状细胞癌，40%为临床I期。HPV感染率约为77%（68.4 - 85.2），HPV-16是最常见的亚型。在单因素分析（p = 0.004）和多因素分析（p < 0.001）中，感染HPV的患者（平均年龄：62.8岁）比未感染患者（平均年龄：71.4岁）年轻。在多因素分析中，外阴病理组织学类型与HPV感染显著相关（p < 0.001），但在单因素和多因素分析中与其他因素未观察到显著关系。PropAttr模型显示归因估计与单一感染流行率之间存在显著相关性（HPV-16：ρ = 0.806，p < 0.001；HPV-18：ρ = 0.992，p < 0.001；其他12种HR-HPVs：ρ = 于0.880，p < 0.001）。HPV-16与其他12种HR-HPVs之间存在强负相关（ρ = -0.751，p < 0.001），提示在基因型分配中存在竞争相互作用。
越南VC病例中的HPV感染率显著高于其他亚洲人群，表明存在重大的公共卫生负担。我们的研究结果强化了扩大国家HPV疫苗接种计划并纳入先进归因模型以改善HPV相关癌症风险评估的重要性。
