Of all the lesions, HPV 16 was the most frequent genotype. This finding is in accordance with many other studies carried out worldwide . In our study, this genotype was present in 35.3% of total lesions. However, in a previous study carried in our hospital from 1993 to 2000, the HPV 16 presence in the total number of lesions was somewhat higher than at present (39%) . Also, in a recent study carried in a southern region of Spain from 2006 to 2007, this presence was even lower than ours (21.2%) .
As expected, HPV16 presence increased in accordance with the grade of the lesion (15.8% in benign lesions, 26.1% in CIN1 cases, 56.3% in CIN2-3 cases and 71.4% in ICC).
HPV 31 was the second most frequent genotype in CIN1 lesions and in CIN2-3 lesions. In a study carried in an eastern region of Spain, HPV 31 was also the second most frequent genotype in HSIL lesions and the presence found in these (10.8%) was very similar to the presence obtained in our study (10.8%) . Previous meta-analysis reported the second position of HPV 31 in LSILs in Europe [11, 20], and our results confirm this finding.
After HPV 16 and 31, HPV 58 was the third most common genotype found in our study. This event should be explained by the large number of immigrants who arrived in Spain over the past decade from Latin America, where this genotype is the second most frequently detected in HSIL after HPV 16 [13, 19]. However, additional studies are needed to confirm this hypothesis. Moreover, the HPV 58 presence was somewhat higher in CIN1 cases (12.9%) than in CIN2-3 cases (8.2%), but this finding doesn’t have statistical significance attending the 95% confidence intervals used for estimate these percentages (9.6-16.9 versus 4.5-13.7).
Our HPV 58 findings are in accordance with other recent study carried in a south-eastern region of Spain in which HPV 58 was the third most common genotype found and its frequency progressively decreased as lesions showed higher grades of dysplasia . As some authors have reported, this decreasing HPV 58 frequency with the severity of the lesion may indicate that, despite the high frequency of HPV58 found in our area, LSIL caused by HPV58 would have less likelihood to progress to HSIL than a LSIL caused by HPV16 .
Globally, HPV 6 was the fourth most common genotype found in our study. Also, HPV 6 and 11 were the most frequent genotype in benign lesions (respectively, 42.1% and 26.3%); but, surprisingly, HPV 16 was present in third position (15.8%), as a single infection, in this type of lesions.
Some authors have reported that LR-HPV types -such as HPV 6 or HPV 11- are rarely identified as single infections in invasive cervical cancer . In the previous study carried in our hospital, from 1993 to 2000, one case of single LR-HPV type infection in cervical cancer was reported . Our current findings confirm that the detection of a single LR-HPV type (HPV 11) in ICC is a possible event. Further efforts are needed to understand in which conditions these HPV types can indeed induce invasive cervical cancer in rare circumstances.
In our study, the HPV 33 and 52 were the fifth and sixth most common types obtained. HPV 33 presence was basically no difference in CIN1 cases (8.6%) than in CIN2-3 cases (8.9%). This finding is in disagreement with the previously mentioned study carried in a south-eastern region of Spain in which HPV 33 frequency increased in parallel with the severity of the lesion .
One previous meta-analysis reported the seventh position of HPV 52 in HSIL in Europe , although in our study HPV 52 was third in these types of lesions. Therefore, the carcinogenic importance of this genotype is possibly increasing in our region at present.
Regarding the frequency of cases with the HPV 18 genotype is significant in our study that the frequency is not as high as the published in other international series. This data is in accordance with other published studies in Spain, in which HPV type 18 does not appear as a common type in the general population in our country . Also, apparently, the HPV 18 presence was higher in CIN1 cases (7.2%) than in CIN2-3 cases (5.7%), but this finding doesn’t have statistical significance attending the 95% confidence intervals used for estimate these percentages (4.7-10.4 versus 2.6-10.5).
As expected, HPV 16 and 18 presence was appreciably lower in CIN1 cases (32.4%) than in CIN2-3 cases (61.4%). However, in a study carried in a north-eastern region of Spain from 1999 to 2005, the joint frequency of these genotypes was considerably higher (55% in CIN 1 cases, versus 80% in CIN 2 cases and 90% in CIN 3 cases) .
Moreover, in the earliest study carried in our hospital, from 1993 to 2000, the HPV 16/18 frequency was somewhat higher than in our current study (43% in LSIL and 67% en HSIL) . However, in a later study also carried in our hospital, the frequency of 16/18 HPV types was similar to our present study (41% in all types of lesions) . Therefore, the joint frequency of these genotypes and its carcinogenic importance is possibly decreasing over time in our region.
A relationship was found between lesions and HR-HPVs frequency. Thus, these genotypes were found more frequently in CIN2-3 cases (93.7%) than in CIN1 cases (51.0%) or benign lesions (21.1%). The HR-HPVs presence found in our study in CIN2-3 cases (93.7%) was similar to the frequency found in the previous studies carried in a region of northern Spain (88.1%) and in a region in eastern Spain (87.4%) [13, 19].
Another issue worth mentioning is the co-infection occurrence, which seems to be more frequent in CIN1 cases (30.7%) than in CIN2-3 cases (18.4%). This finding is in accordance with the study carried in a south-eastern Spanish region mentioned above ; but it is at variance with the other previously mentioned study carried in a region in eastern Spain, in which the percentages of multiple infections were lower than in our study, and there were no considerable differences between groups of lesions (4.8% in LSIL and 3.7% in HSIL) .
In all types of lesions with multiple infections, the most common pattern of co-infection was double infection with HPV 16 and 58 (6 cases). The same result was found in the previously mentioned study carried in a region in northern Spain . However, the most common pattern of co-infection in HSILs cases was double infection with HPV 16 y 52. It is unknown whether the association of these genotypes can produce a synergistic effect and increase carcinogenic risk. Further efforts are needed to clarify this hypothesis.