氟尿嘧啶和干扰素对生殖道上皮细胞高危型HPV感染的治疗研究及疗效比较

Study on the Treatment of High-Risk HPV Infection of Genital Tract Epithelial Cells with Fluorouracil and Interferon and Comparison of Their Efficacy

摘要: 目的：评估氟尿嘧啶(5-FU)联合干扰素(IFN-α)对生殖道HPV感染清除的疗效分析，并探讨其协同用药剂量、方法、用药周期及其协同作用机制。方法：选取2022~2025年间经我院检验科实验室诊断为高危HPV阳性，TCT正常或阴道镜下活检提示无宫颈阴道上皮内瘤变者214例，其中81例患者选择观察进入空白对照组，其余患者要求治疗进入治疗组，治疗组中88例进入干扰素治疗组，行干扰素治疗3月；21例进入5-FU治疗组，剩余24例进入5-FU + 干扰素联合治疗组：治疗停药3月、6月后复查，观察所有患者上药期间的局部刺激症状，比较两组在HPV转阴率、局部刺激症状及耐受性差异。结果：观察/治疗3月后，空白对照组转阴率39.5%，干扰素治疗组44.3%，5-FU治疗组61.9%，联合治疗组62.5%。四组3月后转阴率整体比较，差异具有统计学意义(χ² = 9.62, P = 0.022 < 0.05)。4组观察/治疗结束6月后的转阴率分别为：39.5%，47.7%，66.7%，70.8%，经χ²检验，差异具有统计学意义(χ² = 27.06, P < 0.001)；空白组和干扰素组HPV转阴率(39.5% vs 47.7%)差异无统计学意义(χ² = 1.158 < 3.841, P > 0.05)。干扰素组与联合治疗组转阴率差异无统计学意义(χ² = 2.497 < 3.841，因此P > 0.05)。4组不良反应发生率比较，轻度 + 中重度不良反应发生率：0%，6.17%，42.09%，45.08%，差异有统计学意义(P < 0.05)。且5-FU治疗组和联合治疗组(5-FU + 干扰素)治疗后6月转阴率66.7%，70.8%，差异无统计学意义(χ² = 0.091 < 3.841, P > 0.05)。结论：小样本研究显示：低浓度1%的氟尿嘧啶治疗生殖道上皮细胞HPV感染3个月、6个月后转阴率可达61.9%，66.7%，效果显著，高于干扰素组的44.3%和47.7%，但差异无统计学意义，可能与氟尿嘧啶组样本量过小有关，需进一步扩大样本量得出更可信的结论。

Abstract: Objective: To evaluate the efficacy of 5-fluorouracil (5-FU) combined with interferon-alpha (IFN-α) in eradicating genital human papilloma virus (HPV) infection, and to explore the dosage, administration mode, treatment course as well as the synergistic mechanism of the combined regimen. Methods: A total of 214 patients diagnosed with positive high-risk HPV in the Clinical Laboratory of our hospital from 2022 to 2025 were enrolled. All patients had normal TCT results, and cervical and vaginal intraepithelial neoplasia was excluded by biopsy under colposcopy. According to patients’ willingness, 81 patients were assigned to the blank control group receiving regular observation only; the rest received drug treatment and were divided into three subgroups: 88 cases in the interferon monotherapy group (treated with interferon for 3 months), 21 cases in the 5-FU monotherapy group, and 24 cases in the combined 5-FU plus interferon group. Reexaminations were performed at 3 months and 6 months after drug withdrawal. Local irritation reactions during medication were recorded. The HPV negative conversion rate, incidence of local adverse reactions and drug tolerance were compared among the four groups. Results: After 3 months of observation or treatment, the HPV negative conversion rate was 39.5% in the blank control group, 44.3% in the interferon treatment group, 61.9% in the 5-fluorouracil (5-FU) treatment group, and 62.5% in the combined treatment group. The overall difference in the 3-month negative conversion rates among the four groups was statistically significant (χ² = 9.62, P = 0.022 < 0.05). At 6 months following the completion of observation or treatment, the negative conversion rates of the four groups were 39.5%, 47.7%, 66.7% and 70.8%, respectively; chi-square test demonstrated a statistically significant intergroup difference (χ² = 27.06, P < 0.001). No statistically significant difference was observed in HPV negative conversion rates between the blank control group and the interferon group (39.5% vs 47.7%, χ² = 1.158 < 3.841, P > 0.05). Likewise, there was no significant difference between the interferon group and the combined treatment group (χ² = 2.497 < 3.841, P > 0.05). The incidence of adverse reactions (combining mild and moderate-to-severe adverse events) across the four groups was 0%, 6.17%, 42.09% and 45.08%, respectively, with statistically significant differences (P < 0.05). In addition, the 6-month negative conversion rates were 66.7% in the 5-FU monotherapy group and 70.8% in the combined regimen group (5-FU plus interferon), and the difference between the two groups was not statistically significant (χ² = 0.091 < 3.841, P > 0.05). Conclusion: Results of this small-sample study revealed that topical 1% low-concentration 5-FU yielded HPV negative conversion rates of 61.9% at 3 months and 66.7% at 6 months for genital epithelial HPV infection, presenting satisfactory therapeutic efficacy. The curative effect was numerically superior to that of interferon monotherapy (44.3% at 3 months, 47.7% at 6 months), yet no statistically significant difference was identified, which may be attributed to the limited sample size of the 5-FU group. Further studies with enlarged sample sizes are required to draw more reliable conclusions.