Cervical cancer always occurred at the confluence of squamous and columnar epithelial cells in the cervicovaginal or transitional zone [1-3]. Worldwide, each year, about 200,000 women die from the cervical cancer, while 500,000 new cases occur [4]. Human papillomavirus infection has been confirmed as a cause of cervical cancer [5]. A number of studies have shown that cervical lesions have a long period of precancerous lesions before transformed into malignant tumors [6], that is, there is a time sequence relationship between human papillomavirus (HPV) infection and cervical cancer. The time interval from the beginning of infection to the development of cervical cancer is about 10 to 15 years [7]. Therefore, the effective “three steps” (naked eye observation/HPV/TCT), early detection, diagnosis and treatment can prevent the occurrence of cervical cancer [8]. The detection of HPV infection can indicate the risk of cervical cancer, which is of great significance for early diagnosis and prevention of cervical cancer. There are many genotypes of HPV. The HPV virus family contains more than 200 genotypes; among them, more than 40 genotypes could spread through the genital tract easily. Fourteen HPV genotypes were considered as the pathogenic or “high-risk” for causing the development of the cervical cancer. Even though most sexually active females were infected with HPV for one time in their lifetime, while less than 10% of women become persistently infected. It is the ‘persistent’ infection with a high-risk genotype HPV that contributed to the cervical cancer development. The specific subtypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82 are related to the cervical cancer. In order to effectively avoid the risk of cervical cancer, accurate genotyping for HPV is of great significance. TCT is a common method for early screening of cervical cancer. HPV combined with TCT is critical for the early screening and treatment of cervical precancerous lesions.

In recent years, the incidence of malignant tumors increased. Cervical cancer was one of the most common tumors in women, which seriously affected women’s health. The persistent infection of high-risk HPV was one of the most important causes of cervical cancer and cervical intraepithelial lesions, which has been confirmed by researches. Moreover, the infection of high-risk HPV could promote the abnormal lesions or value-added of cervical epithelial cells, and increase the risk of epithelial malignant cells breaking via the basement membrane and epithelial tissue damage [11,12]. Therefore, the HPV infection monitoring is an important link in the prevention and treatment of cervical cancer, which can be detected in advance via pre pregnancy examination or routine physical examination, so as to achieve the related early diagnosis and treatment.

The relationship between HPV infection and age was analyzed in this report. We found that the HPV infection is related to age. The infection rate of patients over 60 years old was highest, which reached 12.42%, and the second was 52–60 years old, which was 12.32%. The results showed that women who are in perimenopause and postmenopause were susceptible population. It was suggested that more attention should be paid to the detection of HPV in the higher age stage, especially in the population of over 60 years old. The relationship between age and HPV infection rate in this research showed slightly difference with the results in Jijings’ results [13], which may be related to the deviation caused by population distribution. The population in this work selected was located in the city, while the population in Jijing’s result was mainly from the village.

The infection rate of HPV subtype has been also studied. The results indicated that the infection rate of HPV was 1.40%~27.30%, usually about 10.00% [14,17]. In addition, Boda also tested the cervical swab samples from 713 females with genital warts, and tested the samples for high- and low-risk genital HPV [18]. In this work, we found that the infection rate of HPV in Xi’an was 10.76%, which was consistent with the above results. In mainland China, HPV16 is the primary type of HPV, HPV18 the second major type, HPV58 and HPV52 represent the third and fourth type respectively [15]. In this research, we found that 15 high-risk types were detected in 9714 HPV positive samples, the top three types were 52 (16.24%), 58 (11.08%), 16 (11.00%), respectively. There were significant regional differences in HPV infection, and different subtypes of HPV had different carcinogenicity [16]. These results suggest that HPV52, 58 and 16 were more likely to be associated with cervical precancerous lesions in Xi’an. The HPV vaccine for cervical cancer prevention in Xi’an can mainly target specific types of 52, 58 and 16, respectively. However, since the observation and detection time of this study was only last for 2 years, the sample size will be further expanded for the further investigation to clarify the HPV typing. In addition, whether type 52 and 58 also exceed type 16 in other regions of mainland China remains to be further investigated. This work suggested that the prevention of cervical cancer and the research of HPV and vaccine in each region should be carried out according to the high pathogenic subtype in this region, which is beneficial to reduce the missed diagnosis rate of primary screening of cervical cancer. Moreover, the suspected high-risk type 53 infection rate was at a high level of 11.31%, ranked the second place, which may be related to cervical lesions. Therefore, we should pay great attention to it. In this study, single infection was significantly higher than that of multiple infection, however the positive rate of TCT in multiple infection was higher than that in single infection. It was consistent with the findings of Harper [19], which showed that multiple infection was more likely to cause cytological changes than single infection. Therefore, multiple HPV infection should be paid more attention to in clinical.

The appearance of TCT results and HPV infection subtype has improved the positive detection rate. The value of this method lies in the part of the region where HPV typing is not available. It could save all the collected cells in the cell preservation solution, and could timely fix to avoid cell degeneration. Through specific gravity centrifugation, removing the mucus, impurities and inflammatory cells in the specimen, and make a smear with clear field of vision and three-dimensional structure, which is detachable. The great improvement of cytology technology improved the quality of production, reduced the false-positive rate, and further enhanced the identification and sensitivity of pathological doctors to abnormal cells. However, there was still a certain rate of missed examination, for the strong subjectivity of film reading physicians, and the unified diagnostic standards of each region. A single morphological cytology examination may lead to several false negatives. Meanwhile, the detection of HPV pathogens could effectively avoid the missed diagnosis. This work showed that in 9714 HPV patients, TCT results were mainly inflammatory. The results of TCT were as-cus and above, both of which were positive in 100 cases. The positive rate of TCT accounted for 9.57% of the HPV. The top three subtypes of TCT were the same as HPV. In this study, we found that the cytological abnormality of type 58 was higher than that of the other types, which may result in higher pathogenicity of type 58 in Xi’an area. This result suggested that in the screening of cervical lesions in this area, we should strengthen the follow-up management of type 58 infected ones. The results indicated that if there was no condition for processing HPV detection in this city or even in this province, if TCT results show as-cus or above, HPV may be combined with TCT. For type 58 infection, HPV detection can be recommended. Meanwhile, patients with type 52 or 16 infection and normal TCT at present, critical attention should be paid to follow-up to avoid further development of the disease. For persistent HPV infection of 58, 52 and 16 types, clinicians should be reminded to patients to screen TCT regularly to prevent the disease.

To summarize, this work analyzed the HPV infection status, genotyping characteristics, and their correlation with TCT in the physical examination of women in Xi’an area, provided basis for the prevention of different subtypes of HPV and the development of the related vaccines in this area. This work is valuable for achieving early detection and treatment and reducing the incidence of cervical cancer in this area.

Conceptualization, XFL, HYC, XL; Method, XFL, YYW; Software, YXS; Validation, GJZ; Formal Analysis, XFL; Investigation, XL; Resources, HYC; Data management, XFL; Writing, draft preparation, XFL; Project management, XL; Fund application, XFL. All authors read and approved the final manuscript.

The study was approved by the insititutional review board (CWO) of The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shanxi Province. The ethics committee’s reference number is XITU1AF2020L5K-056. All patients provided written informed consent.

The authors are grateful to Dr. Haiyue Guo, Prof. Lijun Guan, Dr. Yue Jin, Dr. Jiang Yu, Mr. Zhanyi Shi, and Dr. Xinjia Qian for their efforts in data collection.

This research received no external funding.

The authors declare no conflicts of interest.