九价HPV疫苗所针对的高危型HPV亚型在宫颈癌及其癌前病变中应用有效性的初步预测

Preliminary prediction of the effectiveness of high-risk HPV types included 9-valent HPV vaccine in uterine cervical cancers and precancerous lesions

背景与目的:宫颈癌是世界范围内女性第4常见的恶性肿瘤,在我国其发病率和死亡率都呈上升趋势,高危型人乳头状瘤病毒(high-risk human papillomavirus,hr HPV)持续感染与浸润宫颈癌(invasive cervical carcinoma,ICC)及其癌前病变的发生、发展关系密切,HPV预防性疫苗的研制应用成为宫颈癌一级预防的有效措施。该研究拟通过分析九价HPV疫苗所针对的7种HPV高危亚型(HPV16、18、31、33、45、52和58)在经组织学证实的宫颈癌及癌前病变中的分布,为九价疫苗在本地区人群的应用前景评估提供更多依据。方法:回顾性收集复旦大学附属肿瘤医院病理科行聚合酶链反应-反向点杂交法(polymerase chain reaction-reverse dot blot,PCR-RDB)进行HPV基因分型检测的患者,经计算HPV阳性患者中特定HPV亚型的阳性比例来评价HPV亚型对宫颈癌及其癌前病变的相对贡献。采用比例权重归因(proportional weighting attribution,PWA)方法将多重感染中亚型占比折算至相应的单型别感染。结果:符合入组条件者共计624例,分别为117例未见上皮内病变及恶性病变(negative for intraepithelial lesion or malignancy,NILM),45例低级别鳞状上皮内病变(low-grade squamous intraepithelial lesion,LSIL),268例高级别鳞状上皮内病变(high-grade squamous intraepithelial lesion,HSIL)和194例ICC。HPV总感染率为84.29%(526/624),在LSIL、HSIL及ICC组中的感染率分别为71.11%,95.90%及91.75%。HPV16/18 PWA合计占比在LSIL、HSIL和ICC组中依次上升,分别为50.00%、70.44%和91.71%。九价疫苗针对的7种hr HPV的PWA合计占比均较HPV16/18提高,在LSIL、HSIL和ICC中分别为86.34%,98.61%和94.89%。额外增加的5种hr HPV(HPV31、33、45、52和58)的相对贡献在LSIL、HSIL和ICC组中依次下降,分别为36.34%、28.17%和3.18%。结论:九价疫苗额外增加的5种hr HPV型别在本地区有望令更高比例的ICC及癌前病变得到预防,尤其对于LSIL和HSIL的预防有较大改善。

Background and purpose： Cervical cancer is the fourth most common cancer in females worldwide. In recent years, the morbidity and mortality are rising in China. The continued infection with high-risk human papillomavirus（hr HPV） is closely related to the invasive cervical carcinoma（ICC） and the precancerous lesions. The application of HPV prophylactic vaccine has become an effective measure for the prevention of cervical cancer. This study aimed at providing more evidence for the estimation of the potential impact of 9-valent HPV vaccine, by analyzing the distribution of 7 hr HPV types（HPV16/18/31/33/45/52/58）, included in the vaccine, in histologyconfirmed ICCs and precancerous lesions from local women. Methods： Cervical samples with histology follow-up from Fudan University Shanghai Cancer Center were collected for HPV genotyping by polymerase chain reaction-reverse dot blot（PCR-RDB）. Relative contribution of HPV types in ICCs and precancerous lesions was expressed as the percentages of type-specific cases among HPV-positive cases. Multiple infections were incorporated into single infection using the method of proportional weighting attribution（PWA）. Results： A total of 624 cases were obtained, including 117 cases of negative for intraepithelial lesion or malignancy（NILM）, 45 low-grade squamous intraepithelial lesion（LSIL）, 268 high-grade squamous intraepithelial lesion（HSIL） and 194 ICC. The HPV prevalences of all, and of LSIL, HSIL and ICC were 84.29%, 71.11%,95.90% and 91.75%, respectively. The PWA of HPV 16/18 to LSIL, HSIL and ICC were 50.00%, 70.44% and 91.71%, whereas the attribution of HPV16/18/31/33/45/52/58 to LSIL, HSIL and ICC were increased to 86.34%,98.61% and 94.89%, respectively. The addition of 5 hr HPV types（HPV31/33/45/52/58） resulted in the reduction of relative contribution in LSIL, HSIL and ICC, as 36.34%, 28.17% and 3.18%, respectively. Conclusion： With the inclusion of additional 5 hr HPV types, the 9-valent HPV vaccine would likely prevent the occurrence of more ICC and precancerous lesions, and would especially benefit the prevention of LSIL and HSIL in China.