The current theory is that cervical cancer and its precancerous lesions are caused by persistent high-risk human papillomavirus (HPV) infection. However, the answer must be no as to whether medical understanding of cervical cancer and its etiology has reached an optimal state. How to choose the best set of cervical cancer screening techniques and protocols is also a great challenge for clinicians to face nowadays. With the continuous development of new ideas and technologies, new studies and evidence are constantly presented in this field. China Gynecology and Obstetrics Network has selected some of the latest internationally published articles on cervical cancer screening in China to sort out and summarize, and share them with you. Perhaps these three articles will bring revolutionary thinking and changes in the field of cervical cancer screening. Ma Xiaoping, Department of Obstetrics and Gynecology, Jiangsu Provincial Hospital of Integrative Medicine Background of the Times: Worldwide cytologic screening with feedback HPV testing (ASC-US) has been the mainstay of cervical cancer screening for the past decade or so. The 2012 U.S. cervical cancer screening guidelines recommend a combined cytology and HPV test for women aged 30-65 y. In April 2014, the U.S. FDA approved Roche’s Cobas HPV test as a first-line screening test for cervical cancer in women aged 25 y and older. There is a great deal of controversy and disagreement as to whether HPV can be used as a first-line screening method for cervical cancer. There is no clinical data or experience to prove that HPV testing as a first-line screening method is effective in detecting precancerous lesions and early cancers. Professor Chengquan Zhao and colleagues at the University of Pittsburgh and Chinese pathologists and gynecologists conducted three studies on the history of HPV testing in large Chinese samples for cervical cancer, which were published in advance in the July issue of Cancer Cytopathology and the American Journal of Cytopathology online this year, respectively, and the main results are reported below: Relevant study 1: The largest CAP-accredited laboratory in China, on 427 cases of invasive cervical cancer A review of prior high-risk HPV testing and cervical cytology testing (Zheng B,Li Z,Griffith CC,Yan S,Chen C,Liang X,Yang H,Zhao C.Prior high-risk HPV testing and Pap test results for 427 invasive cervical cancers in China’s lrgest CAP-certified laboratory.Cancer Cytopathol.2015 Jul;123(7):428-34.Epub 2015 May 8) The authors obtained high-risk HPV and cytology test results for cases histologically diagnosed as invasive cervical cancer in Guangzhou Jinwei (the largest independent pathology laboratory in China) within one year prior to cancer diagnosis. In the retrospective study, it was found that the HPV negativity rate was 7.5% one year prior to histological diagnosis (97% of cases were tested within 3 months). The negative rates of HPV testing in the year prior to histologic diagnosis were 5% for squamous cervical cancer cases and 25% for cervical adenocarcinoma cases, which is consistent with other studies showing that cervical adenocarcinoma has a higher rate of HPV negativity. In the population of women without established screening procedures, invasive cervical cancer (specifically cervical adenocarcinoma) has a fairly high rate of high-risk HPV negativity and a relatively low rate of negative cytologic testing. The reason for the high HPV-negative rate in patients with cervical adenocarcinoma is unclear, but a possible explanation is that cervical adenocarcinoma is etiologically unrelated to HPV infection (especially rare types of adenocarcinoma, such as micrometastatic adenocarcinoma). Although HPV testing is a highly sensitive method and has been approved as a means of primary screening, patients who had both HPV testing and cytology within 1 year prior to histologic diagnosis had a significantly lower negative rate for cytology than for HPV testing. In addition, the difference between the negative cytology rate and the negative HPV rate was more pronounced in invasive cervical adenocarcinoma. Related study II: A historical review of high-risk HPV and cytology testing in large samples of invasive cervical cancer. (Tao X,Griffith CC,Zhou X,Wang Z,Yan Y,Li Z, Zhao C.History of high-risk HPV and Pap test results in a large cohort of patients with invasive cervical carcinoma: Experience from the largest women’s hospital in china.Cancer Cytopathol.2015 jul;123(7):421-7.Epub 2015 May 8) The authors compiled and analyzed case data from January 2011 to October 2014 from the Fudan University Maternity Hospital with histologically diagnosed invasive cervical cancer. The results of high-risk HPV testing and cytological testing in the 3 years prior to the histological diagnosis of cervical cancer were recorded. During these 46 months, 3714 cases of invasive cervical cancer were diagnosed, 525 patients had a history of HC2 testing within 3 years, while 238 patients had cervical cytology results within 1 year prior to the histologic diagnosis. The overall negative rate of high-risk HPV testing within 1 year prior to diagnosis was 15.5% (74/477), while the negative rate of Pap diagnosis was also 15.5% (37/238). 231 patients had both high-risk HPV testing as well as liquid-based cytology. Nine of them (3.9%) had negative results. Compared to squamous cell carcinoma, cervical adenocarcinoma had a higher prevalence of negative results for either high-risk HPV virus or Pap cytology. Related experiment III: Comparison of the sensitivity of cytology and HPV for detecting the incidence of cervical cancer. (Liang H,Griffith CC,Ma L,Ling B,Feng D,Li Z, Zhao Z.The sensivity of pap cytology and HPV testing to detect incident cervical cancer:Prior testing results in 178 patients with invasive cervical cancer at a large general hospital in chinaJ Am Soc Cytopathol Published online:June 10 2015) The authors analyzed 178 cases with HPV and/or cytology results within 1 year prior to histological diagnosis at the China-Japan Friendship Hospital.Cervical cancer was detected by liquid-based cytology methods and HPV testing was mainly by hybridization capture-2 (HC-2) testing. In this study, 82% of patients presented with symptoms mainly of irregular vaginal bleeding. HPV testing was negative in 9.8% of patients within a short period of time before cervical cancer was diagnosed, while the negative Pap cytology rate was 16.7%, and the negative detection rate was higher in adenocarcinoma than in squamous cell carcinoma. However, the double negative was only 1.3% (1/78). Editor’s note: A very well established national cervical cancer screening program is not yet available in China. Based on the comparison of the three large-scale clinical data described above, such probes use an HPV test (HC2) that has a higher negative rate compared to cytology, especially for patients with cervical invasive cancer (adenocarcinoma of the cervix). This demonstrates the percentage of missed cases with HPV testing alone in screening for cervical cancer. Cytologic testing combined with HPV testing can increase the detection rate of cervical cancer and improve the negative predictive value of cervical cancer screening results, but considering the cost-effectiveness or the higher sensitivity of HPV testing, it is still difficult to determine which is the best test, especially in regions and countries that lack well-established screening procedures. Even though the reality is that there are many issues to be resolved, we believe that as more evidence becomes available, the understanding of cervical cancer screening will become more sophisticated, and the screening methods will be more scientifically based.