HPV檢測可以比傳統細胞學檢查偵測更多癌前細胞
作者：Laurie Barclay, MD
出處：WebMD醫學新聞
April 27, 2010 — 根據線上發表於4月28日BMJ的隨機試驗結果，在完善的篩檢計畫中，初步人類乳突病毒(HPV)篩檢加上細胞學分類，在偵測子宮頸上皮內贅瘤(cervical intraepithelial neoplasia，CIN)第3級方面，比傳統的細胞學檢查更具敏感度。
芬蘭赫爾辛基芬蘭癌症登記中心大規模篩檢登記中心研究主任Ahti Anttila博士等人寫道，評估子宮頸癌篩檢計畫和篩檢方式時，侵犯性癌症的發生率是最具資訊力的標準。我們評估初步HPV DNA篩檢加上細胞學分類對於子宮頸癌、嚴重CIN或原位腺癌(作為相對於CIN III+的混合結果)的影響。
在南芬蘭，從2003年到2005年，共有58,076名婦女(年紀30-60歲)獲邀參加例行性、以人口為基礎的子宮頸癌篩檢計劃，研究對象被隨機篩選接受初步HPV DNA檢測(檢測方法是hybrid capture II)加上細胞學分類(陽性結果時)，或者被分派接受傳統的細胞學篩檢。主要研究終點是2003至2007年間發生的CIN III+案例，從篩檢登記中心和全國癌症登記資料中的連結記錄加以確認。
整體追蹤人年方面，HPV組為95,600婦女-年，傳統組為95,700婦女-年。在追蹤期間，分別有76例和53例CIN III+，分別包括6例和8例子宮頸癌。在HPV組和傳統組的比較方面，所有受邀進行篩檢婦女之CIN III+的相對率(RR)為1.44 (95%信心區間為1.01 - 2.05)，所有參與篩檢之婦女為1.77 (95% CI，1.16 - 2.74)。
正常或陰性結果的婦女，後續CIN III+的RR為0.28 (95% CI，0.04 - 1.17)，子宮頸癌比率方面，受邀進行篩檢之婦女為0.75 (95% CI，0.25 - 2.16)，參與篩檢之婦女為1.98 (95% CI，0.52 - 9.38)。
研究作者們寫道，當整合到完善的篩檢計畫時，初步 HPV篩檢加上細胞學分類，在偵測CIN III+病灶上，比傳統的細胞學檢查更具敏感性，子宮頸癌案例數不多，但是，CIN III惡化之可能性的考量對於預防癌症方面相當重要。
研究限制包括，篩檢參加率相對偏低、研究期間的診斷準則可能有所改變、分析對於侵犯性子宮頸癌之影響的統計強度有限。
研究作者們結論表示，原發性HPV篩檢應優先進行有組織的計畫，如果結果是有利的，則擴展執行到全國，因為各國的子宮頸癌篩檢計畫的特徵和組織細節相當不同，每個計畫都須就它們自己的內容評估新方法。我們認為，在試驗區域之外開始，漸進式執行HPV篩檢。
歐盟執委會、歐洲防癌行動計畫之歐洲子宮頸癌篩檢網絡；芬蘭科學院；芬蘭癌症組織等支持本研究。研究作者們皆宣告沒有相關財務關係。
BMJ. 線上發表於2010年4月28日。
HPV Testing May Detect More Precancerous Cells Than Conventional Cytology
By Laurie Barclay, MD
Medscape Medical News
April 27, 2010 — As part of a well-established organized screening program, primary human papillomavirus (HPV) screening with cytology triage is more sensitive than conventional cytology in the detection of cervical intraepithelial neoplasia (CIN) grade III, according to the results of a randomized trial reported online April 28 in the BMJ.
"The incidence of invasive cancer is the most informative standard in the evaluation of cervical cancer screening programmes and screening methods," write Ahti Anttila, PhD, research director, Mass Screening Registry of the Finnish Cancer Registry in Helsinki, Finland, and colleagues. "We evaluated the impact of primary HPV DNA screening with cytology triage on cervical cancer, severe ...CIN, or adenocarcinoma in situ (as a composite outcome referred to as CIN III+)."
In southern Finland from 2003 to 2005, a total of 58,076 women (aged 30 - 60 years) were invited to take part in the routine population-based screening program for cervical cancer. Participants were randomly selected to undergo a primary HPV DNA test (hybrid capture II) with cytology triage if the result was positive, or to conventional cytologic screening. The primary study endpoint was CIN III+ occurring from 2003 to 2007, as determined from record linkage between files from the screening registry and the national cancer registry.
Total follow-up was 95,600 woman-years in the HPV group and 95,700 woman-years of follow-up in the conventional group. During follow-up, there were 76 and 53 cases of CIN III+, respectively, including 6 and 8 cervical cancers, respectively. For the HPV group vs the conventional group, the relative rate (RR) of CIN III+ was 1.44 (95% confidence interval [CI], 1.01 - 2.05) for all women invited for screening and 1.77 (95% CI, 1.16 - 2.74) for women who participated in the screening.
The RR of subsequent CIN III+ was 0.28 (95% CI, 0.04 - 1.17) among women with a normal or negative test result, and the rate of cervical cancer between groups was 0.75 (95% CI, 0.25 - 2.16) among women invited for screening and 1.98 (95% CI, 0.52 - 9.38) among those who took part in the screening.
"When incorporated into a well established organised screening programme, primary HPV screening with cytology triage was more sensitive than conventional cytology in detecting CIN III+ lesions," the study authors write. "The number of cases of cervical cancer was small, but considering the high probability of progression of CIN III the findings are of importance regarding cancer prevention."
Limitations of this study include relatively low screening attendance rate, potential fluctuations in diagnostic criteria during the study period, and limited statistical power to analyze any impact on invasive cervical cancer.
"Primary HPV screening should be piloted in an organised programme, and extension towards a national implementation should be considered if the outcome is favourable," the study authors conclude. "As characteristics and organisational details between cervical cancer screening programmes are highly variable in different countries, each programme needs to evaluate the new methods in their own context.... We think that gradual implementation of HPV screening in regions other than those in this trial is justified."
The European Commission, Europe Against Cancer action programme through European Cervical Cancer Screening Network; the Academy of Finland; and the Cancer Organisation of Finland supported this study. The study authors have disclosed no relevant financial relationships.
BMJ. Published online April 28, 2010.
