Triage human papillomavirus testing for cytology-based cervical screening in women of different ages in primary hospitals
在初级医院对不同年龄女性进行基于细胞学的宫颈筛查的人瘤病毒分流检测

Abstract 抽象

1. Introduction 1. 引言

Cervical cancer is the fourth most common cancer of women worldwide.^[1] According to the National Central Cancer Registry of China in 2015, the incidence of cervical cancer was 98.9 per 100,000 women, and the mortality rate was 30.5 per 100,000 women.^[2] In contrast to the declining trend of cervical cancer incidence in developed countries, the incidence of cervical cancer in China has significantly increased. Hence cervical cancer is still one of the main threats to women's health in China.
宫颈癌是全球女性第四大常见癌症。^[1] 根据 2015 年中国国家癌症中心部资料，宫颈癌发病率为每 100,000 名女性 98.9 人，死亡率为每 100,000 名女性 30.5 人。^[2] 与发达国家宫颈癌发病率的下降趋势相反，中国宫颈癌的发病率显著增加。因此，宫颈癌仍然是中国女性健康面临的主要威胁之一。

Cervical screening has been implemented in some rural and urban areas in women aged 35 to 59 and 35 to 64 years since 2009.^[3] The on-going policy for cervical screening is to perform cytology-based cervical tests for women every 3 years within primary care. However, in primary hospitals, the detection of high-risk human papillomavirus (HR-HPV) is not widely implemented. It is recommended that patients with abnormal cytology undergo a cervical biopsy. Cervical cancer screening work throughout China has not been evenly distributed, with various regions having different conditions. Nevertheless, HR-HPV screening has been implemented as the triage of equivocal cytological results in some places.
自 2009 年以来，一些农村和城市地区已对 35 至 59 岁和 35 至 64 岁的妇女进行了宫颈筛查。^[3] 宫颈筛查的现行政策是在初级保健机构内每 3 年为女性进行一次基于细胞学的宫颈检查。然而，在初级医院，高危人瘤病毒 （HR-HPV） 的检测并未得到广泛实施。建议细胞学异常的患者进行宫颈活检。中国各地的宫颈癌筛查工作分布不均，不同地区的病情不同。尽管如此，HR-HPV 筛查已在一些地方作为模棱两可的细胞学结果的分类实施。

With the improvement of screening technologies, cervical pap smear, and visual inspection with acetic acid and Lugol's iodine are currently only used in remote and economically deficient areas in China. Thin-prep cytologic Test (TCT) screening has become the primary screening method in China.^[4,5] However, the TCT has low predictive value in detecting high-grade cervical cancer precursors, as its accuracy depends on sample acquisition, as well as the skill and experience of the physician.^[6]
随着筛查技术的进步，宫颈巴氏涂片、醋酸和卢戈碘肉眼检查目前仅在中国偏远和经济不足的地区使用。薄制备细胞学检测 （TCT） 筛查已成为中国的主要筛查方法。^[4,5]然而，TCT 在检测高级别宫颈癌前体方面具有较低的预测价值，因为其准确性取决于样本采集以及医生的技能和经验。^[6]

Many studies have shown that most invasive cervical cancers (ICCs) are caused by HR-HPV infection.^[7,8] The persistence of HR-HPV infection in epithelial cells of the cervix is essential to progression towards high-grade cervical disease and ICC.^[9] Without treatment, the risk of ICC increases with an increasing degree of dysplasia by affecting about 50% of women with cervical intraepithelial neoplasia grade 3 (CIN3).^[10] Human papillomavirus (HPV) screening techniques have the advantages of good reproducibility, easy training, and high sensitivity. Recent findings have suggested that HPV DNA detection on self-collected cells has advantages.^[11] TCT, combined with HPV detection, significantly improves the screening sensitivity and specificity for cervical cancers. However, it may not be suitable for women in primary hospitals because it is expensive. Therefore, the value of TCT and/or HR-HPV testing for primary screening is mostly unknown. There is also a lack of evidence and reliable data on the differences in the efficacy of TCT and/or HR-HPV detection methods in women of different ages.
许多研究表明，大多数浸润性宫颈癌 （ICC） 是由 HR-HPV 感染引起的。^[7,8]HR-HPV 感染在宫颈上皮细胞中持续存在对于进展为高级别宫颈疾病和 ICC 至关重要。^[9] 如果不治疗，ICC 的风险会随着异型增生程度的增加而增加，影响约 50% 的 3 级宫颈上皮内瘤变 （CIN3） 女性。^[10] 人瘤病毒 （HPV） 筛查技术具有重现性好、易于培训和灵敏度高等优点。最近的研究结果表明，对自采集细胞进行 HPV DNA 检测具有优势。^[11] TCT 与 HPV 检测相结合，显著提高了宫颈癌的筛查敏感性和特异性。但是，它可能不适合初级医院的妇女，因为它很昂贵。因此，TCT 和/或 HR-HPV 检测对初步筛查的价值大多是未知的。也缺乏关于 TCT 和/或 HR-HPV 检测方法在不同年龄女性中的疗效差异的证据和可靠数据。

Therefore, it is of great importance to find a screening program that has specific sensitivity and specificity in primary hospitals. The objective of this study was to compare and evaluate the efficacy of TCT and HR-HPV screening methods for cervical cancer in adults of different ages to find an optimal screening method that can improve the sensitivity and specificity of detection, save medical costs, and reduce overdiagnosis and treatment for women in primary health care institutions.
因此，在基层医院找到具有特定敏感性和特异性的筛查计划非常重要。本研究的目的是比较和评价 TCT 和 HR-HPV 筛查方法对不同年龄成人宫颈癌的疗效，以寻找可以提高检测灵敏度和特异性、节省医疗费用、减少初级卫生保健机构女性过度诊断和治疗的最佳筛查方法。

2. Materials and methods 2. 材料和方法

3. Results 3. 结果

A total of 9765 women aged 35 to 64 years were included in this study (Table ​(Table1).1). They were divided into 3 groups according to age: 35 to 44 (n = 3211), 45 to 54 (n = 4101), and 55 to 64 (n = 2453) years old.
本研究共纳入 9765 名年龄在 35 至 64 岁之间的女性（表 （表1）。1）. 他们根据年龄分为 3 组：35 至 44 岁 （n = 3211）、45 至 54 岁 （n = 4101） 和 55 至 64 岁 （n = 2453） 岁。

Table 1 表 1

Comparison of thin-prep cytologic test examination results in different age groups.
不同年龄组薄制备细胞学检查结果的比较。

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3.2. HPV-DNA typing test results among different age groups
3.2. 不同年龄组的 HPV-DNA 分型检测结果

Patients with abnormal cytology (n = 241) and normal cytology but clinical suspicious cervical lesions (n = 196) were advised to undergo triage HPV DNA testing. Valid results for both cytology and HPV were obtained for 437 women (Table ​(Table2).2). Among the women with normal cytology, the prevalence of HR-HPV and LR-HPV infection were 4.1% and 0.5%, respectively. Among women with abnormal cytology, 25.7% (62/241) had HR-HPV infection, and 2.1% (5/241) had LR-HPV infection. Among the 67 HPV positive women with abnormal cytology, 48 had ASC-US, 6 had ASC-H, 2 had HSIL, and 11 had LSIL. Five of the women with LR-HPV infection had ASC-US. The proportion of having HR-HPV statistically differed between women with abnormal cytology and normal cytology significantly (P < .001) (Table ​(Table2),2), but with no significant difference among the different age groups (P = .299) (Table ​(Table33).
建议细胞学异常 （n = 241） 和细胞学正常但临床可疑宫颈病变 （n = 196） 的患者进行分流 HPV DNA 检测。437 名女性的细胞学和 HPV 均获得有效结果（表 （表2）。2）. 在细胞学正常的女性中，HR-HPV 和 LR-HPV 感染的患病率分别为 4.1% 和 0.5%。在细胞学异常的女性中，25.7% （62/241） 为 HR-HPV 感染，2.1% （5/241） 为 LR-HPV 感染。在 67 例细胞学异常的 HPV 阳性女性中，48 例为 ASC-US，6 例为 ASC-H，2 例为 HSIL，11 例为 LSIL。其中 5 例 LR-HPV 感染女性患有 ASC-US。细胞学异常和细胞学正常女性的 HR-HPV 比例在统计学上存在显著差异 （P < .001） （表 （表2），2），但不同年龄组之间没有显著差异 （P = .299） （表 （表33）。

Table 2 表 2

Comparison of human papillomavirus and pathological results with cytology results^∗.
人瘤病毒和病理结果与细胞学结果的比较^∗。

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Table 3 表 3

Comparison of human papillomavirusdetection and pathological results in different age groups.
不同年龄组人瘤病毒检测和病理结果的比较。

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3.4. Accuracy evaluation of TCT and HPV DNA test
3.4. TCT 和 HPV DNA 检测的准确性评价

AUC across all age groups was 0.70 to 0.90, indicating that the accuracy of the 2 screening methods for diagnosis CIN1⁺ was moderate (Table ​(Table4).4). The highest sensitivity and specificity for TCT and HPV DNA were all in the 35- to 44-year age group. For TCT, the highest sensitivity and specificity was 87.0% (95% CI: 73.2%–100%) and 56.3% (95% CI: 47.1%–65.4%), respectively. While for HPV DNA, the highest sensitivity and specificity was 60.9% (95% CI: 40.9%–80.8%) and 97.3% (95% CI: 94.3%–100%), respectively. The lowest sensitivity and specificity for TCT was 73.9% (95% CI: 61.2%–86.6%) and 48.9% (95% CI: 41.5%–56.2%) in the 45- to 54-year age group, respectively. While the lowest sensitivity and specificity for HPV DNA was 48.0% (95% CI: 28.4%–67.6%) and 93.6% (95% CI: 86.6%–100%) in the 55- to 64-year age group, respectively. The Youden index of HPV testing was higher than that of TCT detection in the different age groups (0.582 vs 0.432, 0.553 vs 0.228, 0.416 vs 0.332, respectively) (Table ​(Table55).
所有年龄组的 AUC 为 0.70 至 0.90，表明 2 种筛查方法诊断 CIN1⁺ 的准确性为中等（表 （表4）。TCT 和 HPV DNA 的敏感性和特异性最高均在 35 至 44 岁年龄组中。对于 TCT，最高敏感性和特异性分别为 87.0% （95% CI： 73.2%–100%） 和 56.3% （95% CI： 47.1%–65.4%）。而对于 HPV DNA，最高的敏感性和特异性分别为 60.9% （95% CI： 40.9%–80.8%） 和 97.3% （95% CI： 94.3%–100%）。在 45 至 54 岁年龄组中，TCT 的最低敏感性和特异性分别为 73.9% （95% CI： 61.2%–86.6%） 和 48.9% （95% CI： 41.5%–56.2%）。而在 55 至 64 岁年龄组中，HPV DNA 的最低敏感性和特异性分别为 48.0% （95% CI： 28.4%–67.6%） 和 93.6% （95% CI： 86.6%–100%）。不同年龄组 HPV 检测的约登指数高于 TCT 检测的约登指数（分别为 0.582 对 0.432、0.553 对 0.228、0.416 对 0.332）（表（表 55）。

Table 4 表 4

Area under the curve of thin-prep cytologic test and human papillomavirus test tests for the diagnosis of cervical intraepithelial neoplasia grade1 and more severe lesions in different age groups^∗.
薄制备细胞学试验和人瘤病毒试验用于诊断不同年龄组 1 级宫颈上皮内瘤变和更严重病变的曲线下面积^∗。

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Table 5 表 5

Diagnosis-related evaluation indicators of 2 diagnostic methods in different age groups^∗.
不同年龄组 2 种诊断方法的诊断相关评价指标^∗。

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4. Discussion 4. 讨论

Primary hospitals have the main task of national free screening for cervical cancer in China. This study shows the value of detecting cervical cancer and precancerous lesions using primary TCT screening and triage HPV DNA testing in different age groups in the primary care setting. In the present study, we retrospectively analyzed women with abnormal cytological in an organized free cervical cancer screening program based on cytology screening strategy to perform triage HPV-DNA testing before referral to colposcopy to evaluate the value of HPV testing, with the goal of optimizing the strategy of current cervical cancer screening and providing some references. According to previous studies, the detection rate of cervical precancerous lesions increases with increasing age.^[13,14] The results of this study showed that there was indeed a difference in the detection rate of cervical precancerous lesions in different age groups. Moreover, it also demonstrated that cervical histopathological results increased with age (P = .018).
基层医院的主要任务是全国免费筛查宫颈癌。这项研究表明了在初级保健环境中使用初级 TCT 筛查和分流 HPV DNA 检测在不同年龄组中检测宫颈癌和癌前病变的价值。在本研究中，我们回顾性分析了基于细胞学筛查策略的有组织的免费宫颈癌筛查项目中细胞学异常的女性，在转诊阴道镜检查前进行 HPV-DNA 分流检测，以评估 HPV 检测的价值，以优化当前宫颈癌筛查策略并提供一些参考。根据以往的研究，宫颈癌前病变的检出率随着年龄的增长而增加。^[13,14]这项研究的结果表明，不同年龄组的宫颈癌前病变检出率确实存在差异。此外，它还表明宫颈组织病理学结果随着年龄的增长而增加 （P = .018）。

In the current study, there was a significant difference in abnormal cytology in different age groups (P = .003). Cytology is the most frequently used primary screening test due to its better sensitivity. The stages of cervical carcinogenesis include the persistence of HPV infection rather than clearance of the virus, which is linked to the development of a high-grade precursor lesion or “precancer”.^[15] Some precancer stages, such as chronic cervicitis, wet squamous changes, and cervical lesions, can be reversed and/or treated if they are detected early enough, which can radically reduce cervical cancer incidence.^[16,17] So, HPV is recommended as a triage testing or co-testing for women with cytology. However, in China, TCT and HPV co-testing has only been conducted in a small number of areas in the National Cervical Cancer Screening Program, which does not include Jiangsu Province. With limited financial support, more women can participate in screening, and the benefits may be more significant. The optimal strategy for cervical cancer screening is to expand screening rates to maximize the benefits of screening while minimizing potential hazards. In our study, women with ASC-US were recommended to undergo triage HPV-DNA testing as an adjunct to cytology. Of these, among 67 HPV positive women with abnormal cytology, 43 had ASC-US, 6had ASC-H, 2 had HSIL, and 11 had LSIL. Five of the women with LR-HPV infection had ASC-US. The proportion with HR-HPV did statistically significantly differed between women with abnormal cytology and normal cytology (P < .001), with increasing age, and the positive rate of HPV increased, but with no significant difference among the different age groups (P = .299). The infection rate of HPV different from the reported by You et al,^[18] which was high in the age groups of 26 to 30 and 51 to 55 years, accounting for 87.7% (71/81) and 79.7% (51/64), respectively, while it was lower in the >55 years group at 28.6% (14/54) in Shandong provinces of China; this difference was considered to be related to the age of the population and size of the sample. Due to its relatively high specificity (97.3%, 94.4%, and 93.6%, respectively) and positive predictive value (82.4%, 73.7%, and 80.0%, respectively) in detecting CIN1+ lesions in the present study, HR-HPV seems to be useful in the triage of repeat ASC-US or worse among different age groups, which reduces the rate of misdiagnosis. However, our results should be interpreted with caution because a selection bias cannot be ruled out, due to the fact that the use of HR-HPV test was not systematic in this setting.
在目前的研究中，不同年龄组的异常细胞学存在显着差异 （P = .003）。细胞学检查是最常用的初步筛查测试，因为它的敏感性更高。宫颈癌变的阶段包括 HPV 感染的持续存在而不是病毒的清除，这与高级别前体病变或“癌前病变”的发展有关。^[15] 一些癌前阶段，如慢性宫颈炎、湿性鳞状细胞改变和宫颈病变，如果发现得足够早，可以逆转和/或治疗，这可以从根本上降低宫颈癌的发病率。^[16,17]因此，建议将 HPV 作为细胞学女性的分诊检测或联合检测。然而，在中国，TCT 和 HPV 联合检测仅在国家宫颈癌筛查计划的少数地区进行，其中不包括江苏省。在有限的经济支持下，更多的女性可以参与筛查，而且好处可能更显着。宫颈癌筛查的最佳策略是提高筛查率，以最大限度地发挥筛查的好处，同时最大限度地减少潜在危害。在我们的研究中，建议患有 ASC-US 的女性接受分流 HPV-DNA 检测作为细胞学的辅助手段。其中，在 67 名细胞学异常的 HPV 阳性女性中，43 名患有 ASC-US，6 名患有 ASC-H，2 名患有 HSIL，11 名患有 LSIL。其中 5 例 LR-HPV 感染女性患有 ASC-US。细胞学异常和细胞学正常女性的 HR-HPV 比例差异有统计学意义 （P < .001），随着年龄的增长，HPV 阳性率增加，但不同年龄组间差异无统计学意义 （P = .299）。HPV 感染率与 You 等人报道的不同，^[18] 在 26 至 30 岁和 51 至 55 岁年龄组中较高，分别占 87.7% （71/81） 和 79.7% （51/64），而 >55 岁组较低，为中国山东省的 28.6% （14/54）;这种差异被认为与人口年龄和样本大小有关。由于在本研究中检测 CIN1+ 病灶的特异性相对较高 （分别为 97.3%、94.4% 和 93.6%） 和阳性预测值 （分别为 82.4%、73.7% 和 80.0%），HR-HPV 似乎有助于不同年龄组重复 ASC-US 或更差的分类，从而降低误诊率。然而，我们的结果应谨慎解释，因为不能排除选择偏倚，因为在这种情况下使用 HR-HPV 检测不是系统的。

For primary hospitals, screening methods should be economical and effective.^[3,19] In other words, the screening rate of cervical cancer and precancerous lesions should be increased as much as possible, and the rate of missed diagnosis should be reduced with minimum economic investment.^[20] Hence, the sensitivity of screening methods should be increased as much as possible. An excellent screening method should not miss any true-positive patients and also exclude all true-negative patients, limiting the economic, and psychological burden on women.^[21]
对于基层医院，筛查方法应经济有效。^[3,19]换言之，应尽可能提高宫颈癌和癌前病变的筛查率，并以最小的经济投入降低漏诊率。^[20] 因此，应尽可能提高筛查方法的敏感性。一种优秀的筛查方法不应该漏掉任何一个真阳性患者，也不应该遗漏所有真阴性患者，从而限制女性的经济和心理负担。^[21]

In this study, the sensitivity of TCT detection was higher than that of HPV DNA testing across all age groups. By contrast, the specificity, positive predictive value for triage HPV testing was significantly higher than that of TCT in all age groups. These results suggest that triage TCT testing is successfully able to diagnose patients with cervical lesions as the primary method of secondary prevention of cervical cancer and is suitable for women of all ages. HR-HPV has a better ability to screen people with virtually no cervical lesions as an auxiliary screening, which should reduce the number of referral colposcopies, thereby preventing unnecessary overtreatment. Katki et al^[22] reported that cumulative risks for cancer of persistent HPV infection, CIN2, and CIN3 were 56%, 2.8%, and 1.1% while follow-up 1 year, respectively; follow-up 2 years were 37%, 4.8%, and 2.0%.
在本研究中，TCT 检测在所有年龄组中的敏感性均高于 HPV DNA 检测。相比之下，在所有年龄组中，分流 HPV 检测的特异性、阳性预测值均显著高于 TCT。这些结果表明，分诊 TCT 检测能够成功诊断宫颈病变患者，作为宫颈癌二级预防的主要方法，适用于所有年龄段的女性。HR-HPV 作为辅助筛查具有更好的筛查几乎没有宫颈病变的人的能力，这应该会减少转诊阴道镜检查的次数，从而防止不必要的过度治疗。Katki 等人^[22] 报道，随访 1 年时，持续 HPV 感染、CIN2 和 CIN3 的累积癌症风险分别为 56% 、 2.8% 和 1.1% ;随访 2 年分别为 37% 、 4.8% 和 2.0%。

Furthermore, a meta-analysis based on the results of RCTs found a significantly lower rate of cervical cancer among women with negative HPV testing results.^[23] Potential adverse effects of colposcopy procedures related to cervical cancer screening included pain, bleeding, discharge, and anxiety.^[24] In the present study, triage HPV testing of repeat abnormal cytology increased its specificity and positive predictive value and reduced the unnecessary injuries to patients.
此外，一项基于 RCT 结果的荟萃分析发现，HPV 检测结果阴性的女性患宫颈癌的几率显著降低。^[23] 与宫颈癌筛查相关的阴道镜检查程序的潜在不良反应包括疼痛、出血、分泌物和焦虑。^[24] 在本研究中，重复异常细胞学的分流 HPV 检测提高了其特异性和阳性预测价值，减少了对患者的不必要伤害。

Some previous studies have shown that HPV-DNA detection is more sensitive but less specific compared with cytology for high-grade CIN.^[25,26] However, the present study had some differences. On the 1 hand, the population of HPV testing was limited. The HPV as a triage testing was conducted based on people with abnormal cytology results before colposcopy referral to exclude more low-risk people, thus reducing the chances of invasive surgery and saving medical costs. On the other hand, CIN1⁺ was used as the endpoint of diagnosis to identify more high-risk populations. These factors can help in the follow-up care of high-risk groups, including repeat TCT test after 12 months. HPV testing alone or co-testing is the main difference between the European and American guidelines: the American guidelines recommend co-testing with HPV and cytology,^[27] while the European guidelines recommend HPV alone.^[28] China has a large population and regional economic distribution. The current cervical cancer screening program in China is implemented in a “3-Step” strategy, including TCT, HPV testing, and colposcopy, and is carried out in a diversified manner, adopting different screening strategies for different groups of people. Opportunistic screening, which aims to screen out abnormal cases at a minimum cost and select the optimal screening method according to local conditions, can bring the most significant benefit to the majority of women at limited medical cost. Therefore, primary hospitals should expand screening coverage of cervical cancer with more options for low-cost screening strategies.
以前的一些研究表明，与细胞学相比，HPV-DNA 检测对高级别 CIN 的敏感性更高，但特异性较低。^[25,26]然而，本研究存在一些差异。一方面，HPV 检测的人群有限。HPV 作为分诊检测，根据阴道镜转诊前细胞学结果异常的人群进行，以排除更多低风险人群，从而减少侵入性手术的机会并节省医疗费用。另一方面，CIN1⁺ 被用作诊断终点，以识别更多的高危人群。这些因素有助于高危人群的随访护理，包括 12 个月后再次进行 TCT 测试。单独进行 HPV 检测或联合检测是欧洲和美国指南之间的主要区别：美国指南建议与 HPV 和细胞学联合检测，^[27] 而欧洲指南建议单独进行 HPV。^[28] 中国人口众多，经济分布区域众多。目前中国的宫颈癌筛查项目以“三步走”策略实施，包括 TCT、HPV 检测和阴道镜检查，并以多元化的方式进行，针对不同的人群采取不同的筛查策略。机会性筛查，旨在以最低的成本筛选出异常病例，并根据当地情况选择最佳筛查方法，能够以有限的医疗费用为大多数女性带来最显著的益处。因此，基层医院应扩大宫颈癌的筛查覆盖面，为低成本的筛查策略提供更多选择。

The strength of the present screening strategy was that it was based on an opportunistic screening based approach focusing on a community health care maternal child health system,^[3] which is a public health service system run by the government of People's Republic of China. The group was organized by the government in primary medical institutions, with clear screening guidelines. The data provided an accurate indication of the cervical lesions and cancer prevalence in the basic population of the region. The limitation of the present study is relatively small of sample size, which may need further large-scale studies to confirm the conclusion.
目前筛查策略的优势在于，它基于基于机会主义筛查的方法，侧重于社区卫生保健妇幼保健系统[^3]，这是中华人民共和国政府运营的公共卫生服务系统。该小组由政府在基层医疗机构组织，有明确的筛查指南。这些数据准确表明了该地区基本人群的宫颈病变和癌症患病率。本研究的局限性是样本量相对较小，可能需要进一步的大规模研究来证实结论。

5. Conclusions 5. 结论

In conclusion, the results of this study indicate that TCT testing is suitable as the primary cervical cancer screening method for women of all ages in primary hospitals. High-risk HPV as triage testing has a high specificity, and positive predictive value, reducing the rate of misdiagnosis, seems to be an excellent triage method for repeat ASC-US, the numbers of referral colposcopies can be reduced to avoid unnecessary overtreatment. At present, there is no unified cervical cancer screening guideline. This study provides a crucial foundation for a unified cervical cancer screening guideline for primary health care institutions.
总之，本研究结果表明，TCT 检测适合作为初级医院所有年龄段女性的初级宫颈癌筛查方法。高危 HPV 作为分诊检测具有很高的特异性，且具有阳性预测价值，降低误诊率，似乎是重复 ASC-US 的极好分诊方法，可以减少转诊阴道镜检查的数量，以避免不必要的过度治疗。目前，尚无统一的宫颈癌筛查指南。本研究为初级卫生保健机构制定统一的宫颈癌筛查指南提供了重要基础。

Acknowledgments 确认

The authors are thankful to Gilmour Tim for his help in preparing the manuscript.
作者感谢 Gilmour Tim 在准备手稿时提供的帮助。

Author contributions

Z-YY: study design, literature search, data acquisition, manuscript preparation, and manuscript editing. X-XQ: study design, literature search, data acquisition, statistical analysis, manuscript preparation. ZD: literature search, data acquisition, statistical analysis, manuscript preparation. Z-HX: study design, the definition of intellectual content, and manuscript review. WJ: definition of intellectual content, manuscript review. Hongxiu Zhang orcid:0000-001-5995-6460

Writing – review & editing: Hongxiu Zhang.

Glossary

References

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