Park Nora Jee-Young, Park Claire Su-Yeon, Jeong Ji Yun, Kim Moonsik, Yoo Su Hyun, Chong Gun Oh, Hong Dae Gy, Park Ji Young
Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 41404, Korea.
Clinical Omics Research Center, School of Medicine, Kyungpook National University, Daegu 41405, Korea.
Diagnostics (Basel). 2022 Jul 31;12(8):1855. doi: 10.3390/diagnostics12081855.
Infection with high-risk (HR) Human Papillomavirus (HPV) is associated with the development of precancerous lesions or invasive carcinoma of the uterine cervix. Thus, the high viral load (VL) of HR-HPV DNA currently serves as a representative quantitative marker for cervical cancer. However, the clinical significance of low HPV DNA VL remains undetermined. This study aimed to evaluate the clinical association between the low HPV DNA VL and cytology/histologic diagnosis of cervical samples. We searched the electronic medical databases for the resultant analyses of HPV genotyping among patients who underwent treatment for any cervical lesion or who had undergone gynecological examinations with any positive HPV results according to the national cancer screening service between 2015 and 2016. HPV testing with genotyping and semi-quantitative VL measurement was conducted using an Anyplex II H28 Detection assay (H28 assay, Seegene, Seoul, Republic of Korea). The H28 assay is a multiplex semi-quantitative real-time PCR test using the tagging of oligonucleotide cleavage and extension (TOCE) technology. The VL was semi-quantified as high (3+; positive signal before 31 PCR cycles), intermediate (2+; positive between 31 and 39 PCR cycles), or low (1+; positive after 40 PCR cycles). Out of 5940 HPV VL analyses, 356 assays (5.99%) were reported as low VL (1+) of HPV DNA. Matched cytology diagnoses were mostly negative findings (n = 347, 97.5%), except for seven cases of atypical squamous cells of undetermined significance (1.9%) and two cases of atypical glandular cells (0.6%). During the follow-up periods, abnormal cytologic diagnoses were identified, including one case of high-grade squamous intraepithelial lesion (HSIL) and two low-grade squamous intraepithelial lesions (LSILs). The matched, confirmative histologic diagnosis of HSIL cytology was compatible with chronic inflammation, wherein the two LSILs had regular check-ups. None revealed clinically concerned outcomes associated with HPV-related squamous lesions. The cytology was most likely negative for malignancy when the VL of HPV DNA was low (1+). Additional strategic monitoring and management may thus be unnecessary.
高危（HR）人乳头瘤病毒（HPV）感染与子宫颈癌前病变或浸润性癌的发生有关。因此，目前HR-HPV DNA的高病毒载量（VL）作为宫颈癌的代表性定量标志物。然而，低HPV DNA VL的临床意义仍未确定。本研究旨在评估低HPV DNA VL与宫颈样本细胞学/组织学诊断之间的临床关联。我们检索了电子医学数据库，以获取2015年至2016年间根据国家癌症筛查服务接受任何宫颈病变治疗或HPV检测结果呈阳性的妇科检查患者的HPV基因分型分析结果。使用Anyplex II H28检测法（H28检测法，Seegene，韩国首尔）进行HPV基因分型检测和半定量VL测量。H28检测法是一种使用寡核苷酸切割和延伸（TOCE）技术标记的多重半定量实时PCR检测方法。VL被半定量为高（3+；31个PCR循环前呈阳性信号）、中（2+；31至39个PCR循环之间呈阳性）或低（1+；40个PCR循环后呈阳性）。在5940次HPV VL分析中，356次检测（5.99%）报告为HPV DNA的低VL（1+）。匹配的细胞学诊断大多为阴性结果（n = 347，97.5%），除了7例意义不明确的非典型鳞状细胞（1.9%）和2例非典型腺细胞（0.6%）。在随访期间，发现了异常的细胞学诊断，包括1例高级别鳞状上皮内病变（HSIL）和2例低级别鳞状上皮内病变（LSIL）。HSIL细胞学的匹配、确诊组织学诊断与慢性炎症相符，其中2例LSIL进行了定期检查。均未发现与HPV相关鳞状病变相关的临床关注结果。当HPV DNA的VL较低（1+）时，细胞学最有可能为恶性阴性。因此，可能无需额外的战略监测和管理。
