Cervical cancer is a multistep disease and persistent infection with HR-HPV is the major cause of intraepithelial neoplasia and cervical cancer. An efficient preventive and therapeutic strategy including vaccine consideration and HPV testing needs to determine the HPV genotypes distribution in different cervical lesions. Previous Tunisian studies has been conducted on cervical cancer or women with normal pap smear [4, 17]. To our Knowledge, there is few epidemiologic data concerning HPV genotypes in cervical neoplasia from Tunisia. Our study provides results about HPV genotype distribution in different stages of cervical lesions that could be useful for a global preventive strategy of CC and therapeutic algorithms for CIN including vaccine implementation and HPV testing.
The mean age of participants in our study was 38.97 years and 54.5% were over 40 years. The mean age of HPV positive women was 39.56 years old. In our study population we found that there are two age peaks of HPV infection prevalence in women with cervical neoplasia: under 30 years old and over 50 years old. The infection rate during these ages was significantly higher than in the other age groups, suggesting a “U”-shaped infection. In most studies the highest peak is seen in younger women (under 25 years old) then a decreasing trend with age is observed and another maximum peak around 50 years old [18, 19].
In our population study, global HPV prevalence in cervical lesions was 83%. Our data showed that 65% of patients with CINI, 82% with CINII/CINIII and 85% with CC were HPV positive. These results are concordant with other studies conducted in center of Tunisia [1, 7–9, [20] which shows that global prevalence is 73,6%; 84% in CINI and 83,9% in CC. Our results are also consistent with those in most other studies in the word [21, 22]. A recent study in Morocco showed that HPV infection was 92,5% in CC [23]. The HPV positivity in Longnan-China women was 74,6% in CINI, 87,5% in CINII/CINIII and 89,05% in CC [24].
We can conclude that despite the small size of our subgroup, our results are consistent with most reports, which prove the performance of our method of HPV detection and genotyping. Our date reflects the real association pattern between HPV infection and cervical intraepithelial neoplasia subgroup.
Of all HPV positive simples, there was a great proportion of patients with multiple HPV types (43%), but without correlation between coinfection and age. This is not consistent with other studies [25], which showed age-specific prevalence of multiple HPV infections.
In our series HR-HPV was associated with cervical intraepithelial neoplasia (p < 10− 3). The predominant HR-HPV was HPV 16, 18, 53, 35, 45, 39, 51, 52, 33, 59, 68, 70, 66, 56. HR-HPV were observed in lower age < 30-year group and mostly in women in the age group (40–50). In a study of Guardado- Esatrada M, 2014 [26], it is reported that in CC Mexican patients, the first peak was found in the youngest women 35 ≤ years, the second peak was at 61–65 years and the mean ages of the patients singly infected with HPV16, HPV 18, HPV 45 and HPV 39 were at least 5 years lower than the patients singly or doubly infected with other HPV types and HPV 16, 18, 45 and 39 trends decrease [26]. In karollina Aro et al, 2019 study, it is reported that in CINII/CINIII HPV16 and HPV18 are more common in younger women under 30 years old then over 45 years old [25].
CINI may appear within 4 months after HPV infection and if associated with certain HPV genotypes, could progress to CINII, CINIII and cervical cancer. Assessing HPV genotype among CINI is therefore suitable to identify women at risk of progression. Our results indicate that the most frequent HPV genotypes in CINI in order of decreasing prevalence were HPV31, 33, 39, 52, 56, 68, 70, 51 and HPV 53. The meta-analysis [27] of Guan P et al, 2012 reported that HPV 35, 39, 51, 56 and 68 were present in low and High grade lesions but were low in CC, which prove the low carcinogenic potential of this types.
In our series the most prevalent genotypes in CINII/CINIII were HPV 35, 18, 45 and HPV16. In CC, HPV45, 18, 35 and HPV16 were predominant. HPV 16 and HPV18 were detected in all lesions. Our results are concordant with the meta-analyses of Clifford GM.et al showing that in the fifteen high risk HPV genotypes, HPV16 and 18 were found in approximately 70% of cervical cancer worldwide [28]. We also demonstrate that HPV16, 18 and 45 were detected in CC. HPV45 is mostly present in CINII/CINIII and CC.
In fact, HPV 45 seems to be more frequent in Africa and less in European, American and Asian population [22, 24, 27]. In Europe, HPV16 and HPV18 are the most common types. HPV 58 is the most prevalent in Asia. In Saudi Arabia, the most common genotypes in CC were : HPV16, 18, 31, 45, 56, 59 and HPV73 [29]. In A worldwide meta-analysis of over 115 000 HPV-positive women HPV16, HPV18 were the most prevalent HPV types in cervical lesions, while HPV52 and HPV58 were most prevalent in East Asian women [14]. Other study in India describes HPV16, 18 and 58 as the most common types [15]. The Nano-valent vaccine seems to include all world regions HPV distribution [22, 24].
Our findings show that HPV16, 18, 45, 35, 51,53, 58, 59 and 66 HPV types detected in CINII/III and CC play an important role in the development of cervical cancer neoplasia in Tunisian women. Our results are concordant with other studies in the world [7, 11, 16, 17]. We also demonstrated the increased prevalence of HPV18 associated with CC which is less frequently represented in precancerous lesions as CINI and CINII/III. The higher risk for developing CINIII reported for HPV 18 was described in the Meta-analysis study of Clifford GM, 2003 [28].