A new population-based study has demonstrated an association between a group of human papillomaviruses viruses and an increased incidence of squamous cell carcinomas, adding weight to the emerging body of evidence that one genus of HPV may play a role in nonmelanocytic skin cancers.

The findings, published online July 9 in BMJ (BMJ2010 July 9 [doi:10.1136/bmj.c2986]), showed that seropositivity to more than one of a host of 16 beta HPV types increased the likelihood of being diagnosed with a squamous cell carcinoma. Moreover, the risk increased with the number of beta-HPV types to which a person tested positive. No particular type among the 16 examined was found to increase the risk more than another; the risk merely increased with the number of infections.

People with antibodies to two or three types of beta-HPVs were 1.4 times more likely to have been diagnosed with a squamous cell carcinoma than were healthy controls, after adjustment for factors such as age, sex, and smoking. People positive for more than eight types of beta HPV were 1.7 times more likely to have been diagnosed with a skin SCC. However, no link was found between seropositivity to beta HPVs and basal cell cancers.

For their research, the largest study to date to associate beta HPV and squamous cell skin cancer in a general population, epidemiologist Margaret Karagas, Ph.D., of Dartmouth Medical School, Lebanon, New Hampshire, and colleagues identified and analyzed, from an existing cohort in and around the state, 663 previously diagnosed cases of squamous cell carcinoma and 898 cases of basal cell carcinoma, along with 805 randomly chosen healthy controls from the same region.

Study participants were aged between 25 and 75 years and nearly all were white. None of their carcinomas occurred in genital regions. All were interviewed and had venous blood drawn and analyzed for the presence of beta HPV antibodies. A handful of cases – seven squamous cell and two basal cell, along with seven healthy controls – could not be included in the analysis because of problems with their samples.

Dr. Karagas and colleagues performed subanalyses to identify confounding factors that would influence the risk of developing the cancers. “All risk estimates ultimately were adjusted for or stratified by age, sex, and sun sensitivity, and additionally for cigarette smoking for cases of squamous cell carcinoma,” they wrote. “No other factors appreciably influenced the results.”

Of particular interest to the investigators, though, was one subgroup of people taking glucocorticoids. Previous research had demonstrated links between immunosuppressed organ transplant recipients, beta HPV positivity, and another type of nonmelanocytic skin cancer (Transplantation 1996;61:715-21), so Dr. Karagas’ team identified cases and controls who had never had an organ transplant but had taken systemic glucocorticoids to treat other conditions to determine whether glucocorticoid use, and not transplantation, might be the factor affecting the association.

They found that people who reported having taken glucocorticoids for at least a month did in fact have a higher incidence of squamous cell carcinoma with beta HPV positivity. Notably, the investigators wrote, the odds ratio for squamous cell carcinoma with beta HPV positivity was 3.21 among participants with a history of prolonged glucocorticoid use, and 1.23 among those without such a history.

The finding, they wrote, “suggest that the known association between the human papillomavirus and occurrence of skin cancer in the presence of immunosuppression extends to drugs more commonly used by the general population.”

Another potential risk factor Dr. Karagas and colleagues identified was ultraviolet exposure. Though cases with a history of severe sunburn did not evidence higher cancer risk than that of controls with the same history, the findings that sun-sensitive people were at higher risk “provide some evidence of an interaction between exposure to ultraviolet light and human papillomavirus related risk of squamous cell carcinoma,” they wrote.

However, the investigators cautioned, the findings related to the sun-sensitive and glucocorticoid subgroups had limited statistical power. They also noted that because the vast majority of subjects were white, the findings could not necessarily be generalized further.

Neither Dr. Karagas nor her colleagues declared any conflicts of interest.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

一项新的基于人群的研究表明，一组人乳头状瘤病毒(HPV)与鳞状细胞癌的发生率增加相关，这在原有证据的基础上进一步证明了某种类别的HPV可能在非黑色素瘤性皮肤癌的发病过程中起到了一定的作用。

 

7月9日，《英国医学杂志》(BMJ)在线发表了上述研究结果(BMJ2010 July 9 [doi:10.1136/bmj.c2986])。结果显示，在多达16种β-HPV的血清检测中若不止1种呈阳性，那么被确诊为鳞状细胞癌的几率将会增加。而且，血清检测呈阳性的β-HPV种类越多，出现鳞状细胞癌的风险就越大。在所检测的16种β-HPV中没有特别发现哪一种使风险增加的程度高于其他几种；风险只是随着感染数量的增加而上升。

 

在对年龄、性别和吸烟等因素进行校正后，存在2种或3种β-HPV抗体者被确诊为鳞状细胞癌(SCC)的几率比健康对照者高1.4倍。对于8种以上β-HPV检测呈阳性者，被确诊为皮肤SCC的几率比健康对照者高1.7倍。但β-HPV血清检测呈阳性与基底细胞癌之间不存在相关性。

 

这是到目前为止在一般人群中评价β-HPV与鳞状细胞皮肤癌相关性的规模最大的一项研究。为此，美国新罕布什尔州Lebanon达特茅斯医学院的流行病学专家Margaret Karagas博士及其同事基于新罕布什尔州州内及周边地区的现有队列，确定了663例先前已被确诊为鳞状细胞癌的病例、898例先前已被确诊为基底细胞癌的病例以及805例从该地区随机选取的健康对照者，并对上述人群进行了分析。

 

受试者的年龄介于25~75岁，几乎所有受试者都是白种人。无1例患者的癌症发生于生殖器官区域。对所有受试者进行了采访，并抽取了静脉血样以分析是否存在β-HPV抗体。一小部分病例因血样问题而不能被纳入分析，包括7例鳞状细胞癌患者，2例基底细胞癌患者和7例健康对照者。

 

Karagas博士及其同事开展了亚组分析以确定可能影响癌症发病风险的混杂因素。他们写道：“所有风险估值最终都基于年龄、性别和阳光敏感性进行了校正或分层，对于鳞状细胞癌病例还基于吸烟进行了校正或分层。无其他任何因素会明显影响研究结果。”

 

但研究者尤其感兴趣的是一个服用了糖皮质类固醇的亚组。既往研究表明，免疫抑制的器官移植受者、β-HPV阳性与另一种类型的非黑色素瘤性皮肤癌之间存在相关性 (Transplantation 1996;61:715-21)，于是Karagas博士领导的研究小组确定了从未接受过器官移植但接受过全身性糖皮质类固醇以治疗其他疾病的患者和对照者，以确定糖皮质类固醇的使用，而非器官移植，是否可能是影响这种相关性的因素所在。

 

研究者发现，在自称服用了糖皮质类固醇至少1个月的受试者中，β-HPV阳性鳞状细胞癌的发生率的确较高。研究者写道，值得注意的是，在有糖皮质类固醇长期使用史的受试者中，β-HPV阳性鳞状细胞癌的比值比为3.21；而在没有这一药物使用史的受试者中，比值比为1.23。

 

研究者写道，已知存在免疫抑制时人乳头状瘤病毒与皮肤癌的发病之间存在相关性，以上发现“表明这种相关性可外推至一般人群较常用的一些药物。”

 

Karagas博士及其同事发现的另一个潜在危险因素是紫外线暴露。研究者写道，虽然有重度晒伤史的癌症患者并没有表现出比那些有着同样病史的对照者更高的癌症风险，但对阳光敏感的受试者癌症风险更高“这在一定程度上说明了紫外光暴露与人乳头状瘤病毒相关性鳞状细胞癌风险之间存在某种相互作用。”

 

不过，研究者也提醒道，与阳光敏感性和糖皮质类固醇亚组相关的研究发现的统计学效能有限。研究者还指出，由于绝大部分受试者都是白种人，因此该研究结果不一定适用于其他人种。

 

Karagas博士及其同事均声明无相关利益冲突。

 

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