Berlin Grace V M, Niranjali Devaraj S, Radhakrishnan Pillai M, Devaraj Halagowder
Department of Biotechnology, KITS, Deemed University, Karunya Nagar, Coimbatore-641 114, India.
Gynecol Oncol. 2006 Oct;103(1):113-9. doi: 10.1016/j.ygyno.2006.01.057. Epub 2006 Mar 22.
In uterine cervical cancer, certain oncogenic HPV types are considered as key etiologic factor. But the progression of HPV associated cervical precancerous lesions depends on many other factors such as oncogenes, immune system, anti-viral factors etc. This study is therefore focused on the effect of an important dietary anti-viral factor called All Trans Retinoic Acid (ATRA) on the development of HPV associated cervical cancer as it is found higher in poor socioeconomic people.
We analyzed a total population of 130 including control subjects who have no complaints of uterine cervical lesions and the HPV-6/11, 16/18 infected cases of low grade squamous intraepithelial lesions [SIL], high grade squamous intraepithelial lesions [HSIL], and invasive cancers, for serum ATRA level. This study also focused to find out the association of serum ATRA level with the proliferation status in terms of proliferating cell nuclear antigen (PCNA) expression as it is an anti-proliferation agent and with the grades of cervical lesions, using SPSS statistical package.
The results showed a highly significant negative association for serum ATRA level with different stages of cervical lesions (F = 3.305; P = 0.000) by one-way ANOVA and with intensity of PCNA expression (r = -0.825; P < 0.01) by Pearson's correlation test. A highly significant association was observed for the PCNA expression with the grades of cervical lesions too (F = 37.89; P = 0.000). Further, we found from our data that all the invasive cancer cases were infected with HPV-16/18 and none with HPV-6/11. Hence, we analyzed the association of serum ATRA level with HPV-16/18 infected preinvasive cases in developing invasiveness, by Fisher's Exact Test, using Graph Pad Prism as shown in Table 1. The results show an odds ratio (OR) of 36.93 and a relative risk (RR) of 4.99 with an 95% interval being 2.896 to 8.603, which is significant at the level of P = 0.0001 for the reduced [<0.6 mug/ml] serum ATRA level in developing invasive cancer in HPV-16/18 infected preinvasive cases.
All these results suggest that the serum ATRA level highly influences the progression of cervical lesions to invasive cancer and can be therefore aimed as a marker for progression in combination with HPV-16/18, which helps to enhance the modalities of therapy towards cost effectiveness.
在子宫颈癌中，某些致癌性人乳头瘤病毒（HPV）类型被视为关键病因。但HPV相关宫颈上皮内瘤变的进展取决于许多其他因素，如癌基因、免疫系统、抗病毒因子等。因此，本研究聚焦于一种重要的饮食抗病毒因子——全反式维甲酸（ATRA）对HPV相关子宫颈癌发展的影响，因为在社会经济地位较低的人群中发现其含量较高。
我们分析了总共130人的样本，包括无子宫颈病变主诉的对照受试者以及HPV-6/11、16/18感染的低级别鳞状上皮内病变[SIL]、高级别鳞状上皮内病变[HSIL]和浸润癌病例，检测血清ATRA水平。本研究还使用SPSS统计软件包，旨在找出血清ATRA水平与增殖细胞核抗原（PCNA）表达所反映的增殖状态之间的关联，因为ATRA是一种抗增殖剂，同时分析血清ATRA水平与宫颈病变分级之间的关系。
单向方差分析结果显示，血清ATRA水平与宫颈病变的不同阶段呈高度显著的负相关（F = 3.305；P = 0.000），Pearson相关检验显示与PCNA表达强度呈负相关（r = -0.825；P < 0.01）。PCNA表达与宫颈病变分级也存在高度显著的关联（F = 37.89；P = 0.000）。此外，我们从数据中发现，所有浸润癌病例均感染HPV-16/18，无一感染HPV-6/11。因此，我们使用Graph Pad Prism软件，通过Fisher精确检验分析血清ATRA水平与HPV-16/18感染的癌前病例发展为浸润癌之间的关联，如表1所示。结果显示，对于HPV-16/18感染的癌前病例，血清ATRA水平降低[<0.6微克/毫升]时，发展为浸润癌的优势比（OR）为36.93，相对风险（RR）为4.99，95%置信区间为2.896至8.603，在P = 0.0001水平具有显著性。
所有这些结果表明，血清ATRA水平对宫颈病变发展为浸润癌有高度影响，因此可作为与HPV-16/18联合的进展标志物，这有助于提高治疗方式的成本效益。
