Division of Infectious Diseases, Department of Medicine, Weill Cornell Medical College, New York, NY; and.
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
J Acquir Immune Defic Syndr. 2023 Sep 1;94(1):73-81. doi: 10.1097/QAI.0000000000003231.
Persons with HIV (PWH) experience high rates of human papillomavirus (HPV)-associated cancers compared with the general population. Plasma HPV cell-free DNA (cfDNA) tests are sensitive in patients with known HPV-associated cancers. It is not known whether these tests can screen for invasive cancers in populations with high burdens of nonmalignant HPV disease such as PWH. It was not known whether HPV infection and/or noninvasive anal high-grade squamous intraepithelial lesions (HSIL) alone in this population would result in detectable HPV cfDNA, which would result in a high number of false positives if HPV cfDNA is used to screen for invasive cancers.
We conducted a prospective study of PWH in 2 cohorts: 20 without anal HSIL and 20 with anal HSIL. We tested anal and vaginal swabs for HPV infection, and HPV genotyped the biopsies of anal HSIL. Finally, we performed HPV cfDNA droplet digital polymerase chain reaction to test for HPV16/18/33 from plasma samples.
In the combined cohorts, the median age was 56 years, 12.5% were cisgender women, and none had detectable HIV. In total, 84.6% had prevalent anovaginal HPV infection, including 10 participants with HPV16, 13 with HPV18, and 2 with HPV33 infections. Five and 2 participants had HPV16 and HPV33 detected in anal HSIL, respectively. Despite the high prevalence of HPV infection and anal HSIL, no participant had HPV16/18/33 detectable cfDNA by droplet digital polymerase chain reaction.
These results provide a strong rationale for investigating the use of HPV cfDNA in a screening setting for suspected HPV-related invasive cancers in PWH.
与普通人群相比,人类免疫缺陷病毒(HIV)感染者(PWH)发生人乳头瘤病毒(HPV)相关癌症的几率较高。在已知 HPV 相关癌症患者中,血浆 HPV 游离 DNA(cfDNA)检测具有较高的敏感性。尚不清楚这些检测方法是否可以筛查 HPV 负担较高人群中的侵袭性癌症,如 PWH。也不清楚该人群中 HPV 感染和/或单纯非侵袭性肛门高级别鳞状上皮内病变(HSIL)是否会导致可检测的 HPV cfDNA,如果使用 HPV cfDNA 筛查侵袭性癌症,这将导致大量假阳性。
我们对 2 个队列中的 PWH 进行了前瞻性研究:20 例无肛门 HSIL 和 20 例有肛门 HSIL。我们检测了肛门和阴道拭子的 HPV 感染情况,并对肛门 HSIL 的活检标本进行了 HPV 基因分型。最后,我们对血浆样本进行了 HPV cfDNA 液滴数字聚合酶链反应,以检测 HPV16/18/33。
在联合队列中,中位年龄为 56 岁,12.5%为跨性别女性,均未检测到可检测的 HIV。共有 84.6%的人存在阴道肛门 HPV 感染,其中 10 人感染 HPV16,13 人感染 HPV18,2 人感染 HPV33。5 名和 2 名参与者的肛门 HSIL 中分别检测到 HPV16 和 HPV33。尽管 HPV 感染和肛门 HSIL 的患病率较高,但通过液滴数字聚合酶链反应未检测到任何参与者的 HPV16/18/33 可检测 cfDNA。
这些结果为在 PWH 疑似 HPV 相关侵袭性癌症的筛查环境中研究 HPV cfDNA 的应用提供了有力的依据。