Pap smear與HPV test

HPV and cervical cancer related articles part IV- Pap smear and HPV test

到目前為止，仍舊無法用傳統的方式，在實驗室中將HPV成功的培養與繁衍；目前公認，在宿主細胞內，直接偵測到病毒的去氧核醣核酸（deoxyribonucleic acid；DNA），可以直接證明了HPV感染。羅氏公司開發出cobas® 4800 HPV Test體外檢驗套組（IVD），可在一次分析中，同時偵測與區分出：（1）致癌能力最強之HPV-16；（2）致癌能力次之HPV-18；及（3）致癌能力較弱之12種hrHPV亞型（包括HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68）。根據一項設計嚴謹之大型臨床評估，名為雅典娜（ATHENA）試驗，經過三年臨床追蹤研究，納入41,955名25歲以上婦女，進行cobas® HPV Test檢測，結果為：（1）HPV16（＋）患者，3年內發生CIN3機率為1／4；（2）HPV18（＋）患者，3年內發生CIN3機率為1／9；（3）其餘12型致癌型hrHPV（＋）患者，3年內發生CIN3機率為1／19。因此，cobas® HPV Test於2014年首先獲得美國FDA核准，接著於2015年獲得台灣TFDA核准，可做為「第一線子宮頸癌篩檢」體外診斷試劑（IVD）。美國預防醫學服務工作組織（USPSTF）於2018年，針對30～65歲婦女，正式推薦三個選項：（1）每3年一次Pap smear檢查；（2）每5年一次hrHPV檢測；抑或（3）每5年一次Pap smear加上hrHPV檢測（co-testing）。況且，USPSTF不再強調co-testing是優先推薦選項。Pap smear是偵測子宮頸是否有異常細胞，而HPV DNA test是偵測是否有HPV感染；有高危險型的HPV感染代表處於子宮頸癌病變的高風險，但未必已經產生了細胞病變。若以HPV DNA test作為子宮頸癌防治策略第一線篩檢工具，在婦產學界仍未有共識；衡量台灣整體預防保健政策，仍需由衛福部國健署審慎評估後，再作決定。另一方面，HPV疫苗未來會如何影響族群中HPV病毒型的分佈和子宮癌病變，恐怕仍然是個未知數。隨著子宮頸癌疫苗在世界各國公費施打及推廣，推估子宮頸Pap smear的陽性率及重要性將逐漸降低；或許，未來「每5年一次hrHPV測」，可能會成為30～65歲婦女優先的建議選項與主流。

So far, there is still no traditional way to cultivate and reproduce HPV in the laboratory. It is generally accepted that the deoxyribonucleic acid (deoxyribonucleic acid) is detected directly in the host cell. DNA) can directly prove HPV infection. Roche developed the cobas® 4800 HPV Test (In Vitro Diagnostics; IVD), which can detect and distinguish in the first analysis: (1) HPV- 16 with the strongest carcinogenic ability; (2) HPV-18 with the second strong carcinogenic ability; and (3) 12 hrHPV subtypes with relatively weak carcinogenic ability (including HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68). On the basis of a large-scale clinical evaluation with a rigorous design, the ATHENA trial, after three years of clinical follow-up studies, 41,955 women over the age of 25 were enrolled in the cobas® HPV Test and the results were that: (1) the incidence of CIN3 is 1/4 in HPV 16 (+) patient group after 3 years of follow-up; (2) the incidence of CIN3 is 1/9 in HPV 18 (+) patient group after 3 years of follow-up; and (3) the incidence of CIN3 is 1/19 in the other 12 hrHPV types (+) patient group after 3 years follow-up. Therefore, the cobas® HPV Test was first approved by the US FDA in 2014 and by Taiwan TFDA in 2015 independently as the “first-line cervical cancer screening” in vitro diagnostic reagent (IVD). In 2018, the USPSTF officially recommended three options for women aged 30- 65, (1) Pap smear test every 3 years; (2) hrHPV test every 5 years; or (3) Pap smear plus hrHPV test every 5 years (co-testing). The USPSTF no longer emphasizes that co-testing is the preferred choice. Pap smear detects the presence of abnormal cells in the cervix, while HPV DNA test detects HPV infection; hrHPV infection represents a high risk of cervical cancer, but may not have cytopathic effects. There is still no consensus in the community of obstetrics and gynecology in discussion the issue that whether HPV DNA test can be used as the first-line screening tool is still debate. Considering the Taiwan's health preventive strategy, our Health Promotion Administration, MOHW(Ministry of Health and Welfare) should carefully evaluate this policy before making a decision. On the other hand, how the HPV vaccine will affect the future distribution of HPV types and cervical cancer in populations is still unknown. As the cervical cancer vaccine is applied and pro-moted at public expense in the world, it is estimated that the positive rate and importance of Pap smear will gradually diminish. Perhaps, “hrHPV testing every 5 years” may become the preferred recommendation and mainstream for women aged 30-65 in the future.