A   t the beginning of the study, all women with high-risk HPV underwent colposcopy and biopsy. The results showed that in 100 cases (43.4%) cervical histology showed CIN1 and in 130 cases (56.6%) the result was normal. Fifteen patients had ≥CIN2 on their cervix and were excluded from the study, so 230 patients were included.
 The questionnaire including age, parity, education level, cigarette smoking, opium use, alcohol use, OCP use, marital status, HPV vaccination and comorbidities was completed. After one year, all participating patients were visited and the co-test (including pap-smear and HPV test) was performed. The mean age of participants was 35.6±8.4 years.
Comparing the co-test results with the initial assessment, the results showed that in one year follow-up, 142 (67.1%) patients showed HPV clearance. Also, clearance rate was checked for each of the factors. Baseline characteristics were summarized in Table 1.

The number of patients who had positive result for HPV16, HPV18 and other high risk HPV subtypes at the firs visit was 100, 39 and 141, respectively. In one year follow-up, these numbers changed to 28, 8 and 61.
One hundred and twenty women (52.2%) had normal cytologic study (pap smear) in the first-visit and the number of ASC-US and LSIL results was 57 (24.8%) and 53 (23%), respectively. After one year, 186 patients had normal results and the number of ASC-US and LSIL results was 25 and 18, respectively. Only one patient was presented with ASC-H+HSIL result (Table 2).

Moreover, histologic study of the patients showed that 130 (56.5%) patients were normal and 100 (43.5%) had CIN1 result. One hundred and eight patients underwent punch biopsy in 12 months follow-up, and the number of normal, CIN1 and CIN2 results was 64, 43 and 2, respectively.
Although in case of parity, there was no significant difference in univariate analysis (p=0.147), clearance and no-clearance groups showed a significant difference in multiple logistic regression analysis (95% CI: 0.413-0.941, OR=0624, p= 0.024).
The mean age in the clearance and no-clearance groups was 34.6±8.5 and 37.1±8.0, respectively; so the difference was significant (p=0.028). As mentioned in Table 2, the HPV clearance rate was significantly higher in patients with normal histopathologic result compared with CIN1 (P=0.017); but there was no dramatic difference between HPV types or various cytologic results.

Current studies believe that about 70 % of sexually active women are contaminated with HPV and clear in the coming weeks or months (14, 15). Over time, various articles have introduced different factors about the lack of HPV clearance, which we discussed in this article. We evaluated 230 women of whom 142 (67.1%) were cleared and 88(38.3%) were not. 59% of HPV16 cases, 51.3% of HPV18 cases, and 63.8% of High-risk HPV cases were cleared. Type-specific HPV investigations represented a notable role in some studies (16, 17), especially about HPV16 (18-20). In our study, this difference was not significant.
Present study showed that with increasing age, non-regression of HPV becomes more probable.  One possible reason is that with increasing age, the immune system becomes weak, so the clearance of HPV is more difficult (21). Sevral authors have studied about the effect of age on HPV clearance. Sammarco et al., (22) represented that females aged 22–27 years have a higher risk for persistent high risk HPV, which is in line with Li et al., (23) who believe that this risk is higher in limits of age in comparison with middle-aged women. Some studies showed that early age at first sexual intercourse is also effective in HPV persistence (6, 24).
About 20% of our patients had been vaccinated after positive HPV result, but it was shown that post-HPV-infection vaccination doesn’t seem to be effective in HPV regression. After all, there are still some challenges about efficacy of therapeutic vaccines against HPV infection (25).
In the present study, multiparity was associated with increased risk of HPV persistence, which is coordinated with Kim et al. study (7). They believed the trauma during childbirth could be the probable reason. Cervical histopathology in our study was significantly different between the two groups of normal and CIN1 (P=0.017), which was consistent with the study of Kim et al., (7), but some other studies denied this relationship (26, 27). A possible reason for the negative effect of multiparity on HPV-clearance is the high prevalence of squamous metaplasia in pregnancy (28). Further studies are needed to investigate the pathophysiology of these outcomes.
There are some biological and epidemiological evidence about tobacco carcinogens that affects cervical tissue (29-33), in the present study tobacco and opium users showed no significant difference compared to never-smokers. It should be noted that passive smoking has even shown to cause HPV non-clearance (34). It should be noted that due to some social issues, patients may not report the exact number of parity and their smoking status correctly.
In spite of the findings of our study, alcohol (35) and also hormonal contraceptive (36) consumers might be at higher risk to longer-term HPV infection in other studies. There is also some evidence about synergistic effect of viral load (37) or smoking (34) with alcohol use. Also, sexual behavior (number of lifetime sexual partners, having non-monogamous male partners, etc.) and marital status seems to be important. Previous studies, but not ours show these risk factors are effective in HPV persistence and also in genital warts (8, 38).
Although cytology has been associated with HPV in some studies (11, 39), our study didn’t show this relevance.
In this study with respect to social and cultural issues, many patients did not honestly answer questions about smoking and marital status. It seems that further studies with more follow-up periods could provide more complete findings.  In this study, some possible risk factors such as viral load were not checked. Due to the expansion of potential risk factors and heterogenicity of the present studies, future studies are expected to conduct more comprehensive reviews in this case. Due to the possibility of progression to cervical cancer with HPV persistence, next studies with more cases are recommended.

 

It seems that age, cervical histology and parity at the start of HPV infection are the most important factors for HPV clearance.
In other words, higher age and the histopathology result of CIN1 compared to normal result and multiparity are associated with HPV persistence or even progression.

Funding Source

None.

 

The authors declare no conflict of interest. The ethical code is IR.MUI.MED.REC.1399.358.