Analysis of TCT Combined with HPV Typing Detection in Cervical Lesions Screening of Female Medical Staff in Obstetrics and Gynecology Hospital Analysis of TCT Combined with HPV Typing Detection in Cervical Lesions Screening of Female

Objective: This study was to analyze the physical examination and screening data of female medicalstaff in a maternity hospital in Shanghai, and to study the relationship between liquid-based cytology andhuman papillomavirus (HPV) infection. Methods: TCT results of 1093 female medical staff in the hospital from2015 to 2017 and HPV results of 1085 cases in 2017 were collected. SurePath liquid-based cell preparation wasused for cytology and the segr-21 typing kit was used for HPV detection. The relationship between thepathological results of cervical colposcopy biopsy and HPV infection was studied by single factor and multiplefactor regression analysis. Result: The rate of HPV infection women, who were aged 22-90 years old in thisresearch was 10.0% (108/1085) and increased with age. High-risk HPV infection accounted for 95.37%(103/108), and the major high-risk HPV infection was HPV 52, 53, 58, and 16 in descending order. The 3-yearcytological positive rates were 1.6% and 4.0%, respectively. Sixty-six of the HPV and/or cytologicalpositive cases underwent colposcopy biopsy, and the proportion of cytological positive, HPV positive, HPV16positive, cytological negative in 2015 and 2016 was 41.1%, 19.1%, 60% and 29.7%, respectively. Multiplelogistic regression showed that cytology was an independent risk factor, OR 7.87 (95%CI: 1.85-33.54).


Introduction
Cervical cancer is a malignant tumor that seriously harms women's health. According to the World HealthOrganization, about 70,000 new cases of cervical cancer were found worldwide in 2018, and more than 310,000cases of death because of cervical cancer. The incidence rate of middle-income and low-income Asian andAfrican countries was 76.2% [1]. Human papillomavirus (HPV) infection is recognized as an important cause ofcervical cancer.
At least 13 types of HPV high-risk infections may cause cancer.
Among which, HPV16 and HPV18high-risk subtype infections has a possibility as high as 70% to cause cervical cancer or cervical cancerprecancerous lesions [2]. There are generally different stages before an infection of HPV could become cervicalcancer. The pathological changes of the cervical epithelium can be found by Papanicolaou test. Study shows thatthe incidence of cervical cancer has a younger trend. Since the 1950s, European and American countries haveused Papanicolaou test to perform cervical cancer screening and has greatly reduced the incidence andmortality of cervical cancer [3].
Therefore, there is significant importance and meaning for women to take HPVtest regularly, it will help detecting high-risk HPV infection and thus be treated timely. The cervical liquidbasedcytology method developed in the 1990s has gradually replaced the traditional Pap smear in many countries,further improving the detection rate of cervical lesions. The rise of HPV testing has led to debates about whetherHPV testing can replace cytology as a first-line screening method for cervical lesions. In the 2016 study "TheAmerican College of Obstetricians and Gynecologists. Cervical Cancer Screening and Prevention", it isrecommended that women aged 3-=65 years should give priority to the combination of cytology and HPVscreening [4]. In recent years, studies and guidelines have proposed single HPV testing is a viable screeningmethod for cervical cancer [5]. There has always been a widespread attention and debate on the choice of theright method to detect cervical cancer and that for specific groups.
In China, a number of studies have focused on HPV infection rates [6,7] and pap smear test positive rates [8]. Medical staff is a special occupational group as they have higher awareness of HPV infection than the generalpopulation and have more medical expertise. However, staff at obstetrics and gynecology hospitals are of highriskgroup as they're expected to be exposed to HPV infection. There's relatively small infection rate data of thiscertain group of people and whether the incidence of HPV infection and cervical lesions is higher than ordinarywomen are still unclear. By improving and analyzing the screening data of the hospital's obstetricians andgynecologists, the basic data will be accumulated for the primary prevention and screening methods for highriskgroups in the future. This study analyzed the cytology and HPV characteristics of this specific group ofmedical staff from Shanghai. We also analyzed the effectiveness of various methods to prevent precancerouslesions.

HPV Test Method
The 21 full-type HPV test kit from JIANGSU BIOPERFECTUS TECHNOLOGIES COMPANY, LTD was used for thetest. Thirteen types of high-risk types HPV (16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59 and -68), fivepotential high-risk types (26, -53, -66, -73 and -82), and three low-risk types (-6, -11, -81) were simultaneouslydetected by type-specific primers. The classification of the three HPVs is based on IARC's carcinogenic potentialof HPV, that is, the high-risk type is carcinogenic or highly likely to be carcinogenic; the potentially high-risktype is likely to be carcinogenic; the low-risk type is non-carcinogenic [9] Intracellular single copy gene DNAtopoisomerase 3 was used as a relative quantitative internal reference gene. Both PCR system and amplificationassay is operated according to the product instructions. The result is based on the threshold set by the device.

TCT (Thinprep Cytology Test) Method
TCT was collected and maintained using a Sure Path cervical sampler and preservation solution (Becton,Dickinson and Company, Franklin Lakes, USA). After mixing, 2 ml of the sample was taken for HPV detection,and the remaining samples were used for TCT test.

Statistical Analysis
Data analysis was conducted by using Excel 2007 and SPSS 20.0 (…software). The prescriptive analytics resultswere presented by mean, standard deviation, median and percentile. The HPV infection rate of different agegroups was compared using Chi-Squared Test, the amount and percentage were presented as composition ratio(%). χ2 test was used for univariate analysis and logistic regression was used for multivariable analysis with atest level of α=0.05.

Result Overall Summary
The number of medical stuff who participated in the TCT test
The HPV subtypes were divided into high-risk type, potential highrisk type and low-risktype. The common subtypes of high-risk HPV were HPV52, HPV58, HPV16, etc, the results showed that thenumber of infected people of high-risk HPV was 103 (73.04%).
The common potential high-risk HPV subtypes include HPV53, etc, it has a number of infected people of 26 (18.44%). The common subtypes of low-risk HPVincludes HPV81, and the results showed that the number of infected people was 12 (8.51%) (see Table 3).

Risk Analysis of Positive Test Results
Dividing the histological biopsy results into 2 groups, negative    [10].
The HPV infection rate from the medical examination of women in a First-classHospital at Grade 3 in Beijing was 12.84%. According to the result, infection rate was the highest among womenunder 26 years old and decreases as age grows [11]. The HPV positive rate of women under 39 years old inShenzhen was significantly higher than those of 40 to 49-year-old and of over 50 years old [12]. In Laos,percentage of HPV infection for women in age of 30-54 years old is 47.7% [13]. The HPV infection rate ofmedical staff in our study was 10.84% and was lower than that of hospital specialist outpatients and generalmedical examination. The author believes that it may be related to the target population of this study. Medicalstaff is a special occupational group with has higher awareness of HPV infection than the general populationand more medical expertise. They pay more attention to personal protection in daily life and have better diseasedetection as well as treatment.
These can all be some of the reasons why the HPV infection rate is lower for themedical staff than the general population.
On the other hand, the HPV subtypes of infection in this study vary a lot. In this study, the most popular infectionsubtype is HPV52, 53, 58 and 16. While in the past, most researches are concentrated in types of HPV16, 52, 58and other high-risk subtypes [14,15].
HPV16 is classified as a high-risk HPV and have been confirmed by studiesthat its persistent infection is significantly associated with advanced cervical cancer [16]. Same correlation wasfound in our study. However, the correlation disappears in multiple logistic regression analysis. The possiblereasons for that could be the limitation of number of samples or TCT test positive rate was higher than that of HPV test.  with histologywas found except for HPV16 in this study. Therefore, in future research, we can expand the sample size of thesurvey population, conduct research on the correlation between the highly pathogenic HPV type and histology,and even explore the highly pathogenic HPV type of the Chinese population for further independent detection.That will effectively increase the specificity of HPV as a screening for cervical lesions. This providesindependent test a significant meaning especially while using as primary screening in remote areas with scarcecytological diagnostics by reducing medical costs and improving screening rate.