HIV 感染者低的CD4/CD8 比值預示其癌症風險增加
資料來源：基思.奧爾康 / 2022 年 4 月 11 日 / aidsmap news / 財團法人台灣紅絲帶基金會編譯
圖片來源：Jarun Ontakrai/Shutterstock.com
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美國的一項大型研究確定了一種免疫系統信號，該信號警示HIV感染者在診斷罹患幾種常見癌症前兩年的風險增加。
該研究發現，低 CD4/CD8 比值與在未來 6 個月至 2 年的追蹤期間內發生任何形式癌症的風險增加有關。但在控制其他癌症風險因素後的更精確分析顯示，CD4/CD8 比值可能對識別需要更密集篩查肺癌或肛門癌的人特別有用。
與普通人群相比，HIV感染者罹患癌症的風險更高，不僅部分原因係免疫抑制，但也因為導致癌症之病毒的盛行率和吸煙更高。
已顯示低 CD4 計數可預測在某些非 AIDS 定義之癌症上有更高風險，但人們有興趣在識別上可能更敏感的其他生物標誌。一個潛在的標誌是 CD4/CD8 比值。
CD4/CD8 比值顯示 CD4 計數與 CD8 細胞計數的比率。在一般人群中，該比率通常高於 1。一項針對病毒載量受到抑制的 HIV 感染者的大型國際研究顯示，CD4/CD8 比值會隨著時間的推移而提高，但在CD4 計數低才開始治療的人群中，其CD4/CD8 比值不太可能接近正常水平。研究顯示，經過八年的治療，CD4/CD8 比值之中位數為 0.8。
低 CD4/CD8 比值顯示高水準的免疫激活、T 細胞衰竭和 T 細胞複製性衰老，其中 T 淋巴細胞失去對感染因子正確反應的能力。 T 細胞衰竭和 T 細胞複製性衰老是衰老的特徵，並且與癌症發展的風險增加有關。
與北美愛滋病世代研究與設計合作組織 (the North American AIDS Cohort Collaboration on Research and Design , NA-ACCORD) 相關的研究人員，想要了解HIV感染者之 CD4/CD8 比值是否為癌症風險增加有用的預測指標。他們的分析發表在《國家癌症研究所雜誌》上。
NA-ACCORD 結合了北美HIV感染者的世代。 15 個在 1998 年至 2016 年間收集癌症診斷信息的世代對分析做出了貢獻，其中包括最近 12 個月被追踪的所有世代成員。它排除了在加入世代研究時患有癌症或在加入世代後六個月內患上癌症的人。
研究人群主要是男性（86%），43% 是白人，37% 是黑人，11% 是拉丁裔。在研究開始時， CD4 細胞中位計數為 437， CD4/CD8之中位比值為 0.47。 21% 患有丙型肝炎，7% 患有乙型肝炎，29% 有大量飲酒史，33% 有吸煙史。
本研究中的大多數人在研究開始時正在接受抗反轉錄病毒治療或在追蹤期開始後不久開始治療。 58% 的人在追蹤期開始時檢測不到病毒載量。
在研究期間，對 83,893 名 HIV 感染者進行了 744,415 人年的追蹤，診斷出 5,628 例癌症（6.7% 的世代在中位追蹤 8.5 年期間患上了癌症）。
最常診斷的癌症是前列腺癌（801 例）、肺癌（755 例）、卡波西肉瘤（501 例）、非霍奇金淋巴瘤（497 例）、肛門癌（439 例）、肝癌（347 例）和結直腸癌（221 例）。
為了評估 CD4/CD8 比值對罹患癌症風險的影響，研究人員將兩個值（0.3 和 0.5）與 0.8 的比值進行了比較，並研究了在癌症診斷前 6 個月、12 個月、18 個月和 24 個月與低的 CD4/CD8 比值相關的不同風險，他們稱之為滯後的 CD4/CD8 比值。
6 個月滯後的 CD4/CD8 比值為 0.3 或更低，會使任何癌症的風險增加 24%。當考慮到 24 個月滯後的 CD4/CD8 比值，風險增加幾乎相同 (23%)。
在特定癌症方面，低 CD4/CD8 比值（0.3 或更低）與非霍奇金淋巴瘤、卡波西肉瘤、肺癌、肛門癌和結直腸癌的風險增加相關，而6月滯後的 CD4/CD8 比值和其他的時間點，在這幾種癌症之間的風險差異很小，除了非霍奇金淋巴瘤，其滯後 6 個月的比值比滯後的 24 個月比值與更高的風險相關。
但對於其他幾種癌症，低滯後 6 個月的 CD4/CD8 比值相較在其他任何時間點都不會增加罹患癌症的風險。宮頸癌、頭頸癌、前列腺癌、乳腺癌和肝癌的風險不受CD4/CD8比值的影響，霍奇金淋巴瘤的風險僅在考慮12個月和18個月滯後比值時才會增加.
了解更多：CD4/CD8 比值
在一項控制 CD4 計數、吸煙、飲酒和體重的多變量分析中， 6 個月低的滯後 CD4/CD8 比值與任何癌症、非霍奇金淋巴瘤、肺癌和肛門癌的風險增加有關。
該研究的作者說，他們研究的優勢在於所研究的人口規模和記錄的大量癌症。他們說需要進一步的研究來確定 CD4/CD8 比值是如何、以及何時可用於 HIV 感染者的癌症篩查，但他們得出結論，CD4/CD8 比值「可能是篩查肺癌和肛門癌的有用生物標誌物」。HIV感染者的平均診斷年齡比一般人群年輕」。
參考文獻
Castilho JL等人：成年HIV感染者的 CD4/CD8 比值和癌症風險。美國國家癌症研究所雜誌，2022 年 3 月 16 日線上發表。
DOI：https://doi.org/10.1093/jnci/djac053
Low CD4/CD8 ratio predicts increased cancer risk in people with HIV
Keith Alcorn / 11 April 2022
Jarun Ontakrai/Shutterstock.com
A large US study has identified an immune system signal that warns of an increased risk of several common cancers in people living with HIV up to two years ahead of diagnosis.
The study found that a low CD4/CD8 ratio was associated with an increased risk of developing any form of cancer in future follow-up periods of between six months and two years. But more precise analysis that controlled for other risk factors for cancer shows that the CD4/CD8 ratio may be especially useful for identifying people who require more intensive screening for lung cancer or anal cancer.
People with HIV have a higher risk of cancer than the general population, due in part to immunosuppression but also because of higher prevalence of viruses that cause cancer and of smoking.
Low CD4 count has been shown to predict a higher risk of some non-AIDS-defining cancers but there is interest in identifying other biomarkers that might be more sensitive. One potential marker is the CD4/CD8 ratio.
The CD4/CD8 ratio shows the ratio of CD4 count to CD8 cell count. In the general population, the ratio will usually be above 1. A large international study of people with HIV with suppressed viral load shows that the CD4/CD8 ratio improves over time but is less likely to approach the normal level in people who started treatment with a low CD4 count. The study showed that after eight years on treatment, the median CD4/CD8 ratio was 0.8.
A low CD4/CD8 ratio indicates high levels of immune activation, T-cell exhaustion and T-cell replicative senescence, where T-lymphocytes lose the ability to respond correctly to infectious agents. T-cell exhaustion and T-cell replicative senescence are features of ageing and are associated with an increased risk of cancer development.
Researchers associated with the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) wanted to find out whether the CD4/CD8 ratio is a useful predictor of increased cancer risk in people with HIV. Their analysis is published in the Journal of the National Cancer Institute.
NA-ACCORD combines cohorts of adults with HIV in North America. Fifteen cohorts that collected information on cancer diagnoses between 1998 and 2016 contributed to the analysis, which included all cohort members who had been followed for at last 12 months. It excluded people who had cancer at the time they joined a cohort study or who developed cancer within six months of joining a cohort.
The study population was predominantly male (86%), 43% were White, 37% Black and 11% Latinx. The median CD4 cell count was 437 and the median CD4/CD8 ratio was 0.47 at study entry. Twenty-one percent had hepatitis C and 7% had hepatitis B, 29% had a history of heavy alcohol use and 33% had a history of smoking.
The majority of people in this study were taking antiretroviral therapy at study entry or began treatment soon after the follow-up period began. Fifty-eight percent had an undetectable viral load at the beginning of the follow-up period.
During the study period, 83,893 people with HIV were followed for 744,415 person-years and 5,628 cancers were diagnosed (6.7% of the cohort developed cancer during a median follow-up of 8.5 years).
The most frequently diagnosed cancers were prostate cancer (801 cases), lung cancer (755 cases), Kaposi’s sarcoma (501 cases), non-Hodgkin lymphoma (497 cases), anal cancer (439 cases), liver cancer (347 cases) and colorectal cancer (221 cases).
To assess the impact of CD4/CD8 ratio on the risk of developing cancer, the researchers compared two values (0.3 and 0.5) to the ratio of 0.8 and also looked at the differing risks associated with low CD4/CD8 ratios 6 months, 12 months, 18 months and 24 months prior to cancer diagnosis, which they term the lagged CD4/CD8 ratio.
A six-month lagged CD4/CD8 ratio of 0.3 or below increased the risk of any cancer by 24%. The increase in risk was almost identical (23%) when considering the 24-months lagged CD4/CD8 ratio.
In terms of specific cancers, a low CD4/CD8 ratio (0.3 or less) was associated with an increased risk for non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer and colorectal cancer, again with little difference in risk between the six-month lagged CD4/CD8 ratio and other time points, except for non-Hodgkin lymphoma, where the lagged six-month ratio was associated with a higher risk than the lagged 24-month ratio.
But for several other cancers, a low lagged six-month CD4/CD8 ratio did not increase the risk of cancer at any time point. The risks of cervical cancer, head and neck cancer, prostate cancer, breast cancer and liver cancer were not affected by CD4/CD8 ratio, and the risk of Hodgkin lymphoma was only increased when the 12-month and 18-month lagged ratios were considered.
Find out more: CD4/CD8 ratio
In a multivariable analysis that controlled for CD4 count, smoking, alcohol consumption and body weight, a low six-month lagged CD4/CD8 ratio was associated with an increased risk of any cancer, of non-Hodgkin lymphoma, lung cancer and anal cancer.
The study authors say that the strength of their study lies in the size of the population studied and the large number of cancers recorded. They say that further research is needed to define how and when the CD4/CD8 ratio can be used in cancer screening in people with HIV, but they conclude that CD4/CD8 ratio “may be a useful biomarker for screening for lung and anal cancer in people with HIV where the average age at diagnosis is younger than in the general population.”
References
Castilho JL et al. CD4/CD8 ratio and cancer risk among adults with HIV. Journal of the National Cancer Institute, published online 16 March 2022.
DOI: https://doi.org/10.1093/jnci/djac053