The evaluation of cervicovaginal fluid Alpha-actinin-4 (ACTN4) levels in patients with high risk genital HPV infections

Cervical squamous cell lesions are commonly seen in reproductive aged women. HPV type 16 and 18 are responsible for more than two-thirds of lesions. The rate of spontaneous regression within two-three years is nearly 90%. However permanent and/or latent HPV infection in the form of re-infection or re-activation are responsible for dysplasia progression. Therefore close follow-up visits are needed in women with genital HPV infection and new alternative diagnostic methods are under development with the aim of early diagnosis of persistent HPV. Alpha-actinin 4 (ACTN4) is a protein with an actin-binding properties and has a role in remodelling of actin cytoskeleton. It is demonstrated that elevated vaginal ACTN4 levels might have role in cervical dysplasia progression. For this reason we evaluated the relation between vaginal fluid ACTN4 levels and squamous cell lesions in patients with high risk genital HPV infection. A total of 104 patients were grouped according to high risk HPV type and cervical cytological results as follows: Group1: HPV type 16 and/or 18 (+) and cytology ≥ ASCUS, Group 2: HPV type 16 and/or 18 (+) and benign cytology, Group 3: HPV type non-16/18 (+) and cytology ≥ ASCUS, Group 4: Two years of persistent HPV type non-16/18 (+) and benign cytology, Group 5: Histologically diagnosed HSIL regardless of HPV and cytology type and Group 6: Negative HPV and benign cytology. 44.2% (n: 46) of patients were HPV type 16-18 positive and the remaining 46.2% (n:48) were HPV non-16-18 positive. Cervical cytology were benign in 39.4% (n: 41), ASCUS in 29.8% (n: 31), LSIL in 24% (n: 25), ASC-H in 3.8% (n: 4), HSIL in 1.9% (n: 2) and AGC in 1% (n: 1) of patients. Cervical biopsy results were benign in 25% (n: 24), CIN I in 42.7% (n: 41), CIN II in 19.8% (n: 19) and CIN III in 12.5% (n: 12) of patients. The mean vaginal ACTN4 values were measured as follows; 1625.0667.19 pg/ml, 1687.9396.22 pg/ml, 1587.8760.41 pg/ml, 2067.5670.48 pg/ml, 2850.12262.19 pg/ml and 1680.3771.9 pg/ml (MeanSEM) in Group I to VI. Statistically significant difference was detected among vaginal ACTN4 levels between Group I, II, III, VI and Group V (p<0.001). Furthermore there was statistically significant difference among vaginal ACTN4 levels between Group III vs Group IV (p=0.002). In the current case-control study, we found that ACTN4 levels in vaginal fluid were significantly elevated in patients with HSIL independent from type of hr-HPV and/or cervical cytology. As a conclusion we declare to the presence of elevated vaginal ACTN4 levels in patients with HSIL and ACTN4 has potential diagnostic role for the early diagnosis of HSIL in women with high risk genital HPV infection. Furthermore elevated levels of vaginal ACTN4 in women with normal cytology, hr-HPV type non-16/-18 positivity and benign cervical histology or low grade cervical dysplasia (CIN I) might be related with HPV persistence. Key words: HPV Infection, Cervical Dysplasia, Cervical Carcinoma