Diagnostic value of high-risk HPV E6/E7 mRNA in patients with ASCUS

Cervical cancer is one of the most common malignant tumors in women. There are approximately 100,000 new cases of cervical cancer in China every year [1]. The mortality rate of cervical cancer has surpassed that of ovarian cancer and it has become the malignant tumor with the highest mortality rate among gynecological tumors [2]. With the improvement of people’s health awareness, an increasing number of cervical epithelial lesions are found by cervical liquid-based thin layer cytology (TCT). As an uncertain diagnosis, ASCUS has a high detection rate in the Bethesda (TBS) system, which leads to the low accuracy of TCT screening [3]. In 2013, ASCCP recommended the HPV DNA test as a basis for the management of patients with ASCUS, but its specificity was low, and the false-positive rate was high. It was later reported that, compared with HPV DNA detection, HPV E6/E7 mRNA detection has high sensitivity and good specificity in high-grade cervical precancerous lesions, and it can be used as an effective means of further diagnosing patients with ASCUS [4,5,6].

Persistent infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer [7]. Among them, HPVl6 and 18 types are the most common in the clinic, and patients with HPVl6/18 coinfection are more likely to develop high-grade lesions (CINII +) [8]. A total of 81.8% of CIN II + patients are HPV16 positive, and 18.1% of patients are HPV18, 31, 33, or 45 subtype positive [9]. It is suggested that the screening and testing of HPV DNA should pay attention to these HPV types [10]. However, in addition to subtypes 16 and 18, it is controversial whether the increasing number of patients positive for other subtypes should be referred for colposcopy and cervical biopsy. Moreover, there is still a lack of clinical management standards and guidance for HPV E6/E7 mRNA-positive ASCUS patients. Therefore, the purpose of this study was to explore the different morbidities of different high-risk subtypes of HPV in patients with ASCUS by analyzing the relationship between the pathological results of biopsy and the results of tests for HPV16, 18/45 and other high-risk subtypes of HPV E6/E7 mRNA in patients with ASCUS to screen for cervical cancer more accurately.

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Studies have reported that 20% of all new cases of cervical cancer occur in women aged 65 and above, who account for 34% of cervical cancer deaths [11]. For postmenopausal women, the HR-HPV test can better predict high-grade cervical lesions than TCT [12]. Regardless of whether the previous screening is negative or positive, close attention should be given to cervical cancer screening in postmenopausal women [13]. At present, there is no difference in the recommendations for cervical cancer screening between premenopausal and postmenopausal women. Few studies have reported HPV mRNA infection and corresponding cervical morbidity in premenopausal and postmenopausal ASCUS patients, so we need more clinical and pathological data on premenopausal and postmenopausal ASCUS women. In this study, premenopausal and postmenopausal women were divided into two groups to analyze the relationship between HPV16, 18/45 and Other HR-HPV infection and the pathological results of biopsy to explore the necessity of further colposcopy referral and biopsy for ASCUS patients. The results of this study will provide a basis for pathologists to improve the diagnosis of ASCUS and to provide feasible suggestions for clinicians to make accurate diagnoses and provide appropriate treatments for patients.

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