Chaturvedi Anil K, Madeleine Margaret M, Biggar Robert J, Engels Eric A
Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Blvd, EPS 7072, Rockville, MD 20852, USA.
J Natl Cancer Inst. 2009 Aug 19;101(16):1120-30. doi: 10.1093/jnci/djp205. Epub 2009 Jul 31.
Although risk of human papillomavirus (HPV)-associated cancers of the anus, cervix, oropharynx, penis, vagina, and vulva is increased among persons with AIDS, the etiologic role of immunosuppression is unclear and incidence trends for these cancers over time, particularly after the introduction of highly active antiretroviral therapy in 1996, are not well described.
Data on 499 230 individuals diagnosed with AIDS from January 1, 1980, through December 31, 2004, were linked with cancer registries in 15 US regions. Risk of in situ and invasive HPV-associated cancers, compared with that in the general population, was measured by use of standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). We evaluated the relationship of immunosuppression with incidence during the period of 4-60 months after AIDS onset by use of CD4 T-cell counts measured at AIDS onset. Incidence during the 4-60 months after AIDS onset was compared across three periods (1980-1989, 1990-1995, and 1996-2004). All statistical tests were two-sided.
Among persons with AIDS, we observed statistically significantly elevated risk of all HPV-associated in situ (SIRs ranged from 8.9, 95% CI = 8.0 to 9.9, for cervical cancer to 68.6, 95% CI = 59.7 to 78.4, for anal cancer among men) and invasive (SIRs ranged from 1.6, 95% CI = 1.2 to 2.1, for oropharyngeal cancer to 34.6, 95% CI = 30.8 to 38.8, for anal cancer among men) cancers. During 1996-2004, low CD4 T-cell count was associated with statistically significantly increased risk of invasive anal cancer among men (relative risk [RR] per decline of 100 CD4 T cells per cubic millimeter = 1.34, 95% CI = 1.08 to 1.66, P = .006) and non-statistically significantly increased risk of in situ vagina or vulva cancer (RR = 1.52, 95% CI = 0.99 to 2.35, P = .055) and of invasive cervical cancer (RR = 1.32, 95% CI = 0.96 to 1.80, P = .077). Among men, incidence (per 100 000 person-years) of in situ and invasive anal cancer was statistically significantly higher during 1996-2004 than during 1990-1995 (61% increase for in situ cancers, 18.3 cases vs 29.5 cases, respectively; RR = 1.71, 95% CI = 1.24 to 2.35, P < .001; and 104% increase for invasive cancers, 20.7 cases vs 42.3 cases, respectively; RR = 2.03, 95% CI = 1.54 to 2.68, P < .001). Incidence of other cancers was stable over time.
Risk of HPV-associated cancers was elevated among persons with AIDS and increased with increasing immunosuppression. The increasing incidence for anal cancer during 1996-2004 indicates that prolonged survival may be associated with increased risk of certain HPV-associated cancers.
尽管艾滋病患者患肛门、宫颈、口咽、阴茎、阴道和外阴的人乳头瘤病毒(HPV)相关癌症的风险增加,但免疫抑制的病因作用尚不清楚,而且这些癌症随时间的发病趋势,尤其是在1996年引入高效抗逆转录病毒治疗之后,并未得到充分描述。
将1980年1月1日至2004年12月31日期间诊断为艾滋病的499230人的数据与美国15个地区的癌症登记处相链接。通过使用标准化发病比(SIR)和95%置信区间(CI),测量原位和浸润性HPV相关癌症与普通人群相比的风险。我们通过使用艾滋病发病时测量的CD4 T细胞计数,评估了免疫抑制与艾滋病发病后4至60个月期间发病率的关系。比较了艾滋病发病后4至60个月期间三个时间段(1980 - 1989年、1990 - 1995年和1996 - 2004年)的发病率。所有统计检验均为双侧检验。
在艾滋病患者中,我们观察到所有HPV相关原位癌(SIR范围从宫颈癌的8.9,95%CI = 8.0至9.9,到男性肛门癌的68.6,95%CI = 59.7至78.4)和浸润癌(SIR范围从口咽癌的1.6,95%CI = 1.2至2.1,到男性肛门癌的34.6,95%CI = 30.8至38.8)的风险在统计学上显著升高。在1996 - 2004年期间,低CD4 T细胞计数与男性浸润性肛门癌风险在统计学上显著增加相关(每立方毫米CD4 T细胞每下降100个的相对风险[RR]=1.34,95%CI = 1.08至1.66,P = 0.006),与原位阴道或外阴癌风险非统计学显著增加相关(RR = 1.52,95%CI = 0.99至2.35,P = 0.055)以及与浸润性宫颈癌风险相关(RR = 1.32,95%CI = 0.96至1.80,P = 0.077)。在男性中,1996 - 2004年期间原位和浸润性肛门癌的发病率(每10万人年)在统计学上显著高于1990 - 1995年(原位癌增加61%,分别为18.3例对29.5例;RR = 1.71,95%CI = 1.24至2.35,P < 0.001;浸润癌增加104%,分别为20.7例对42.3例;RR = 2.03,95%CI = 1.54至2.68,P < 0.001)。其他癌症的发病率随时间保持稳定。
艾滋病患者中HPV相关癌症的风险升高,且随着免疫抑制的增加而增加。1996 - 2004年期间肛门癌发病率的增加表明,延长生存期可能与某些HPV相关癌症风险增加有关。