REBACIN® is an optional intervention for persistent high‐risk human papillomavirus infection: A retrospective analysis of 364 patients

To evaluate the therapeutic efficacy of REBACIN® in patients with persistent high‐risk HPV (hrHPV) infection. Persistent hrHPV infection is a crucial cause of cervical cancer, for which optimal pharmacological intervention remains unavailable.

On the basis of cytology and HPV test results, the risk of cervical cancer can be assessed and the next step determined for its management. Traditional interventions for HPV infection mainly include routine screening, cryotherapy, laser ablation, cervical conization, loop electrosurgical excision procedure, therapeutic HPV vaccine, immunotherapy (e.g. imiquimod and interferon), and antiviral drugs

| MATERIALS AND METHODS
The present retrospective study was approved by the Institutional Ethics Committee of West China Second University Hospital and only included participants who consented orally to the use of their medical records during telephone follow-up. Between September 2015 and February 2019, 364 patients who were continuously infected with HPV for at least 12 months and only treated with REBACIN® were retrospectively analyzed. The inclusion criteria were as follows: (1) sexually active women; and (2) persistent hrHPV infection for more than 12 months. The exclusion criteria were as follows: (1) women who did not complete the designed administration of conventional drugs (REBACIN® was recommended to be used for at least 20 days per month for three consecutive months); (2) women with a fundamental immune deficiency (such as after chemotherapy); (3) women with severe heart, lung, liver, or kidney dysfunction; (4) women with drug allergies; and (5) pregnant or lactating women. The participants were followed up for 3-6 months after their final administration of the drug, as the outcome of HPV DNA typing or HC2 hrHPV DNA tests before and after the REBACIN® intervention were necessary. Besides, the results of the ThinPrep cytologic test and colposcopy can assist with the determination of the drug's efficacy.
The methods of testing were as follows: (1)  of HPV, whereas with regard to the results of the HC2 hrHPV DNA test, it was defined as the rate at which more than 25% of the hrHPV load decreased. [12][13][14][15] The data were analyzed using SPSS software version 22.0 (IBM, Armonk, NY, USA). The counting data were analyzed using the χ 2 test. All the P values reported were two-sided and P<0.05 indicated statistical significance. Moreover, binary logistic regression analysis was used to identify the major factors affecting the efficacy of REBACIN®.
In addition, the terms "(interferon OR interferon-α2b OR recombi-

| RESULTS
The present study had a sample of 364 participants whose general characteristics are listed in

| DISCUSSION
Several studies focused on the time of HPV regression and put for-  Specifically, when a patient tests positive for an HPV 16 or 18 infection, a colposcopy should be performed immediately. 24 Katki et al. 25 also indicated that in 965 360 women, LSIL resulted in a 5-year risk of CIN3+ in 5.2%, but 6.8% were HPV-positive/cytology-negative; the latter were at a higher risk of CIN3+. In the present study, the cytology test before treatment was an influential factor in determining efficacy, and ASCUS or LSIL seemed to have a higher rate of efficacy than rate than the negative one. More attention should be paid to patients with HPV-positive/cytology-negative results, and these patients should be managed appropriately.
In the present study, although sex with or without condoms showed no significant differences, it was recommended that a condom be used while on medication. Correct and consistent use of condoms will reduce the risk of HPV infections. It was found that people who have sex without condoms might be associated with a slightly higher risk of recurrence or may easily acquire a new hrHPV infection. This is evident by the fact that 14 of the 55 patients who did not use condoms had a recurrent or new infection, whereas only 23 of the 218 patients who did not have sex or had sex with condoms developed a recurrent or new infection.
As most patients in the present study chose the REBACIN® intervention (241/272) after the ineffective interferon therapy, information was collected on their interferon therapy history, which showed that the efficacy of REBACIN® was uninfluenced by previous use or non-use of interferon. In other words, REBACIN® showed significant efficacy even in patients in whom interferon therapy was ineffective.
The present study has some limitations. It was a non-randomized, controlled trial, which yielded reliable results. Although there was no control group for the rate of efficacy of interferon, there was an adequate number of participants and a combined retrospective study and meta-analysis was conducted with the same characteristics in the main aspects, ensuring result reliability.

AUTHOR CONTRIBUTIONS
YY, TWYH, and ZYL contributed to the data collection, study concepts, and study design. YY, TWYH, and EY contributed to the literature search and meta-analysis. YY and XM contributed to the data analysis. WJM contributed to the English language editing. All of the authors contributed to the interpretation of data, preparation of the manuscript, and editing and review.