Lancet Oncol：未接種HPV疫苗的HPV陰性老年女性最後一次宮頸癌篩查的年齡和罹患宮頸癌的終生風險

目前，有關停止宮頸癌篩查的年齡的經驗證據少之又少。一般而言，全球範圍內停止宮頸癌篩查的建議年齡是50-70歲。然而，老年女性的宮頸癌發病率和死亡率仍居高不下。研究者們使用篩查宮頸癌的馬爾可夫模型（Markov模型）估測不同年齡、採用不同方式取消篩查的女性罹患宮頸癌的剩餘生命年限的終生風險，旨在為發達國家停止宮頸癌篩查的年齡提供意見參考。研究發表在2018年11月1日的《The Lancet. Oncology》上。

在該建模研究中，研究者們搭建了宮頸癌的自然史和篩查的狀態轉換模型（Markov模型）。利用加拿大省級註冊管理機構和調查數據對該模型進行了搭建、校準和驗證。為了在該模型中模擬年齡結構群體，每年將236,564名女性（2012年20-24歲的加拿大女性人口的五分之一）的數據納入該模型，並且相繼建模。模型中連續隊列的年齡差為10歲，構成一個10歲至100歲的女性年齡結構群體。進行了子宮全切除術的女性不屬於本研究的研究對象。研究者們使用加拿大統計局的數據對模型進行了人乳頭瘤病毒（HPV）感染和宮頸癌發病率的校準，該數據彙編了13個省級註冊管理機構的數據。研究者們選擇了三階進展性宮頸上皮內瘤變模型，該模型包含病變嚴重程度導致的管理和治療決策差異。模擬了四種高風險HPV感染組：HPV16和HPV18感染；HPV31，HPV33，HPV45，HPV52和HPV58感染；HPV35，HPV39，HPV51，HPV56，HPV59，HPV66和HPV68感染；以及一組可能致癌的其他HPV感染。評估了在不同年齡停止篩查並使用不同篩查方法的未接種疫苗的老年女性在5年內、10年內以及剩餘生命年限終生罹患宮頸癌的風險。

年齡在80歲到84歲之間的女性患宮頸癌的風險被低估71%（不包括接受過子宮切除手術的女性）。該研究模型預測，在45名未接種過HPV疫苗且從未接受過篩查的婦女中，有1名（1/45）有終生患宮頸癌的風險（百分位間隔為95%，1/32至1/64）。25歲至69歲的女性在未接種HPV疫苗的情況下，若每3年都堅持進行一次細胞學檢查，患宮頸癌的終生風險可降低至1/532（百分位間隔為95%，1/375至1/820）。將女性停止細胞學檢查的年齡從55歲提高到75歲能夠降低患癌風險。如果一名檢查史不明的70歲女性停止檢查，其平均剩餘生命風險為1/588（

通過細胞學篩查降低宮頸癌風險的年齡可以達到75歲，不過隨著年齡的增加，篩查的作用遞減。未接種過宮頸癌疫苗且具有宮頸的女性在55歲以後終生患宮頸癌的風險低與致癌HPV檢測退出試驗、HPV檢測和細胞學檢查的陰性結果有關。該研究由加拿大衛生研究院贊助。

Background

There is a paucity of empirical evidence to inform the age at which to stop cervical cancer screening. The recommended age to stop screening generally varies between age 50–70 years worldwide. However, cervical cancer incidence and mortality remain high in older women. We used a Markov model of cervical cancer screening to estimate the remaining lifetime risk of cervical cancer at different ages and with different exit screening tests, with the aim of informing recommendations of the age at which to stop cervical cancer screening in developed countries.

Methods

For this modelling study, we developed a state transition (Markov) model of cervical cancer natural history and screening. We developed, calibrated, and validated our model using Canadian provincial registries and survey data. To simulate an age-structured population in the model, a new cohort of 236?564 women (one fifth of the population of Canadian women aged 20–24 years in 2012) entered the model every year and were successively modelled in parallel. Successive cohorts entered the model at age 10 years, creating an age-structured population of women aged 10–100 years. Women who had a total hysterectomy were excluded from the analyses. We calibrated our model to human papillomavirus (HPV) infection and cancer incidence with data from Statistics Canada, which compiles the data from 13 individual provincial registries. We chose a three-stage progressive cervical intraepithelial neoplasia model to include differences in management and treatment decisions depending on lesion severity. We modelled infections with four high-risk HPV groups: HPV16 and HPV18; HPV31, HPV33, HPV45, HPV52, and HPV58; HPV35, HPV39, HPV51, HPV56, HPV59, HPV66, and HPV68; and a generic group of other potentially oncogenic HPVs. We estimated 5-year, 10-year, and remaining lifetime risk of cervical cancer for older, unvaccinated women who stopped screening at different ages and underwent different screening tests.

Findings

Cervical cancer incidence excluding women with hysterectomies underestimated the incidence of cervical cancer in women with a cervix by up to 71% in women aged 80–84 years. Our model predicted that women without HPV vaccination who have been never screened have a 1 in 45 (95% percentile interval 1 in 32 to 1 in 64) lifetime risk of cervical cancer. Perfect adherence (100% of women screened) to cytology screening every 3 years between the ages of 25 years and 69 years could reduce the lifetime risk of cervical cancer to 1 in 532 women (95% percentile interval 1 in 375 to 1 in 820) without HPV vaccination. Increasing the age at which women stopped cytology screening from 55 years to 75 years led to incremental decreases in cancer risk later in life. A 70-year old woman whose screening history was unknown had an average remaining lifetime risk of 1 in 588 (

Interpretation

Cervical cancer risk reductions might be achieved by screening with cytology up to age 75 years, although with diminishing returns. A negative exit oncogenic HPV test or negative HPV test plus cytology correlates with a low remaining lifetime cervical cancer risk for unvaccinated women with a cervix after the age of 55 years.

來源：中國疾病預防控制中心

編輯：ipsvirus

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