宫颈上皮内瘤变（CIN）是一组与宫颈浸润癌密切相关的癌前病变的统称。包括宫颈不典型增生和宫颈原位癌，反映了宫颈癌发生中连续发展的过程，即由宫颈不典型增生（轻→中→重）→原位癌→早期浸润癌→浸润癌的一系列病理变化。CIN一般无明显症状和体征，部分有白带增多、白带带血、接触性出血及宫颈肥大、充血、糜烂、息肉等慢性宫颈炎的表现，正常外观宫颈也占相当比例（10%～50%），故单凭肉眼观察无法诊断CIN。随CIN级别的增高，发展到浸润癌的几率增加，大体上CIN有15%可发展为宫颈癌，其中CINⅠ、Ⅱ、Ⅲ级发展到癌的危险性分别为15%、30%和45%。宫颈上皮内瘤变预后好，经过标准的诊治，能阻断进一步发展至宫颈癌的可能。HPV疫苗对宫颈上皮内瘤变及宫颈癌有一级预防意义。细胞学筛查的广泛开展，联合阴道镜检查及镜下活检有助于早期发现、早期诊断宫颈上皮内瘤变。

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美国《临床肿瘤杂志》2017年5月25日在线先发

http://ascopubs.org/doi/full/10.1200/JCO.2016.71.4543

3 级宫颈上皮内瘤变后 人乳头状瘤病毒相关性癌变 与癌前病变 风险长期持续增加 ：一项以人群为基础的队列研究

目的

本研究旨在了解在诊断为宫颈上皮内瘤变3级（CIN3）的女性中人乳头状瘤病毒（HPV）相关性癌与癌前病变的风险，对这种风险的了解和认识对预防其它HPV相关性癌前病变和癌的发生发展至关重要，了解这种风险就可考虑进行HPV预防性接种，并且一旦甄别出3级宫颈上皮内瘤变（CIN3），就应高度关注其它HPV相关性癌和癌前病变。

方法

我们从荷兰全国组织学病理和细胞学病理登记中心甄别出1990至2010年诊断为宫颈上皮内瘤变3级（CIN3）的女性，并与没有3级宫颈上皮内瘤变的女性对照组匹配。随后，提取出1990至2015年在肛门生殖器区和口咽部有高风险HPV相关性癌和高级别病变的所有患者，对外阴、阴道、肛门和口咽部的癌变和癌前病变发生率的比值进行估算。

结果

共甄别出178036名女性：89018名既往诊断为宫颈上皮内瘤变3级（CIN3）、89018名匹配无3级宫颈上皮内瘤变史的对照。有3级宫颈上皮内瘤变（CIN3）病史的女性表现出HPV相关性癌变、癌前病变的风险增加，肛门癌发生率的比值为3.85（95%CI，2.32-6.37），肛门3级上皮内瘤变发生率的比值6.68（95%CI，3.64-12.25），外阴癌比值4.97（95%CI，3.26-7.57），外阴3级上皮内瘤变13.66（93%CI，9.69-19.25），阴道癌86.08（95%CI，11.98-618.08），阴道3级上皮内瘤变25.65（95%CI，10.50-62.69），口咽癌5.51（95%CI，1.22-24.84）。甚至在长期随访长达20年后，这种风险仍持续显著增加。

结论

这项以人群为基础的研究表明，3级宫颈上皮内瘤变诊断后，肛门与生殖器区域、口咽部HPV相关性癌变及癌前病变的风险长期持续增加。在这类患者中，需要进行诸如密集筛查或强化接种来预防这种风险增加的研究。

《壹篇》南南和北北

Long-Lasting Increased Risk of Human Papillomavirus–Related Carcinomas and Premalignancies After Cervical Intraepithelial Neoplasia Grade 3: A Population-Based Cohort Study

DOI: http://dx.doi.org/10.1200/JCO.2016.71.4543

Purpose

The aim of this study was to determine the risk of human papillomavirus (HPV)–related carcinomas and premalignancies in women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3). Knowledge of this risk is important to preventing the development and progression of other HPV-related premalignancies and carcinomas, by considering prophylactic HPV vaccination and/or by paying increased attention to other HPV-related carcinomas and premalignancies when CIN3 is identified.

Methods

Women diagnosed with a CIN3 between 1990 and 2010 were identified from the Dutch nationwide registry of histopathology and cytopathology (PALGA) and matched with a control group of women without CIN3. Subsequently, all cases of high-risk (hr) HPV–associated high-grade lesions and carcinomas in the anogenital region and oropharynx between 1990 and 2015 were extracted. Incidence rate ratios were estimated for carcinomas and premalignancies of the vulva, vagina, anus, and oropharynx.

Results

A total of 178,036 women were identified: 89,018 with a previous diagnosis of CIN3 and 89,018 matched control subjects without a history of CIN3. Women with a history of CIN3 showed increased risk of HPV-related carcinomas and premalignancies, with incidence rate ratios of 3.85 (95% CI, 2.32 to 6.37) for anal cancer, 6.68 (95% CI, 3.64 to 12.25) for anal intraepithelial neoplasia grade 3, 4.97 (95% CI, 3.26 to 7.57) for vulvar cancer, 13.66 (93% CI, 9.69 to 19.25) for vulvar intraepithelial neoplasia grade 3, 86.08 (95% CI, 11.98 to 618.08) for vaginal cancer, 25.65 (95% CI, 10.50 to 62.69) for vaginal intraepithelial neoplasia grade 3, and 5.51 (95% CI, 1.22 to 24.84) for oropharyngeal cancer. This risk remained significantly increased, even after long-term follow-up of up to 20 years.

Conclusion

This population-based study shows a long-lasting increased risk for HPV-related carcinomas and premalignancies of the anogenital and oropharyngeal region after a CIN3 diagnosis. Studies that investigate methods to prevent this increased risk in this group of patients, such as intensified screening or vaccination, are warranted.

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