HPV has been recognized as the necessary cause of cervical cancer . However, in the present study, awareness of HPV as major risk factor for cacx was very low among the studied population while smoking, hormones, and infections were identified as main risk factors. Previous studies approaching this point came out with the same conclusion of ignorance of association between HPV and cacx [40, 41]. As expected, only 1.5% of studied women, mostly from urban areas, had Pap smear. Three of them mentioned, without documents, having results consistent with invasive lesions. However, their cytological results were normal in this study. This important point highlights the absence of health culture in the population. Studies from other countries, reported that only 5% of women in low and middle income countries received screening, usually in private clinics and few urban settings, contrary to high-income countries where up to 70% of women were screened [1, 42].
ASM cases were positive for HPV 16/18 and 31/33. ASM, a poorly characterized cervical lesion with uncertain biological and clinical significance, shares some but not all morphological features of SIL [43, 44]. It has been shown that HPV positive ASM biopsies were significantly more likely to have concurrent or subsequent diagnosis of HSIL than HPV negative ones [43, 45]. Unfortunately, the actual study is limited by the fact that it covers a single period and had no opportunity to follow up ASM HPV positive cases. The rational for inclusion of ASM was based on the fact that recent studies found HPVs genome incorporated in normal squamous epithelium [22, 46, 47]. However, due to financial restraints, normal tissues were not included, to evaluate the presence/absence of HPVs.
This community based study confirms previous hospital based one reporting low prevalence rate for CIN; analysis of 4458 patients showed a prevalence of 0.36%, 0.23% and 0.12% for CINI, CINII and CINII respectively . In addition, the Middle East Cancer Consortium reported 0.027% prevalence rate for cacx for Egyptian women . The prevalence of EA and HPV infections in Egypt is comparable to other geographical areas in Muslim and Middle East countries. In Saudi Arabia, EA represented 3.14% out of 3088 screened women with ASCUS, LGSIL, HGSIL, invasive SCC, AGCUS and adenocarcinoma represented 0.45%, 0.93%, 0.55%, 0.13%, 0.13% and 0.03% respectively . In Jordan a prevalence of 0.026% has been reported . In Lebanon, a study conducted on 1,026 women revealed a prevalence of 4.9% for HPV with type 16 representing 3% . In Morocco, 70.5% of invasive carcinoma cases were HPV positive, 34.88% cases had HPV16, and 15.5% cases had HPV18 . In Iran, controversial data were reported; 73.9% of HPV positive cacx contained HPV16 , while in another study HPV16 was identified in 26.7% and none of the samples were positive for HPV18 .
Studies showed significant geographic variation in the prevalence of oncogenic viral types in cervical lesions with roughly half of all cacx worldwide containing HPV 16. Other important high risk types are HPV 18, 45, and 31. Less prevalent high risk types include HPV 26, 33, 35, 39, 51, 52, 56, 58, 59, 68, 73, and W13b . In Africa, the most common subtype is HPV 16 followed by 45, 18, 31 and 33 , a point concordant with the actual work. Unskilled workers were at greater risk for HPV infection and other EA. These women were the highest to have husbands with history of genital infection, showed vaginal discharge by examination, reported history of infection and higher sexual activity. HPV infection seemed to be more among women whose husbands ever had another wife or travelled before. In addition, one fourth of unskilled workers had husbands who ever travelled before or married another wife. In spite that the majority of women had married once, 15% of unskilled workers had married more than once. It is clear that the marital/sexual practices of unskilled workers were the determinants of their higher susceptibility to HPV and CIN. The socio-economic characteristics of unskilled workers confirm previous studies where associations have been found between low socioeconomic status [1, 28, 26], multiple sexual partners [56–59] and cacx. Another risk factor, smoking, is added to unskilled workers, as 83% of them were exposed to smoking at home and work. Higher prevalence for high-risk HPV types was significantly associated with cigarette smokers . Steroid contraception has been postulated to be one mechanism whereby HPV exerts its oncogenic effect on cervical tissue especially among long-term users , a point concordant with the present study, mostly noted in one half of unskilled workers. The prevalence of HPV in ASM and other abnormal biopsies may be underestimated due to the fact that the HPV probes used in the study do not cover all the high risk types and include some low risk . Additionally, normal tissues previously shown to harbour the virus [22, 46, 47] were not tested due to financial limitations. A third important point is the use of ISH technology, an insensitive one compared to catalyzed signal amplified colorimetric DNA ISH , to hybrid capture (HC) HPV DNA assay [63–65] or polymerase chain reaction [66, 67]. However, other studies showed that ISH HPV was more predictive of biopsy histopathology in patients with detectable cervical lesions than is HC HPV . Furthermore, the sensitivity of ISH was comparable to that of HC2, with significantly superior specificity, and was therefore thought to be an efficacious alternative to HC2 for triaging patients with abnormal cervical cytology results .
Our data on schistosomiaisis as risk factor for the development of cacx confirm previous studies in Egypt [8, 10] and elsewhere . However, T. vaginalis previously implicated to have direct relation to cacx in the Egyptian population  were not established in the actual work. Moreover, early marriage or early sexual relations, was not significantly associated with HPV as Egyptian women start sexual relations with marriage. Other studies confirmed that women who have their first intercourse at an early age are at high risk for HPV infection and cacx [56, 57, 70]. Being uncircumcised male was found to be a high risk factor , which was not evaluated due to universality of male circumcision among Egyptian men both Moslem and Christians.
The study is limited by the fact that it covers a single period and had no opportunity to examine trends over time. Three obstacles reduced the number of satisfactory smears, noted mostly at the beginning of the study, implying the importance of training. These were, smears not interesting the squamo-columnar junction, inadequate fixation and hemorrhagic smears resulting from traumatisation of the mucosa by the cytobrush. Inadequate biopsies were encountered whenever they were performed in health units using portable colposcope. In addition, women of higher socioeconomic group refusal to participate may have led to missing the chance to describe the pattern of cervical lesions among this group. The drop out of women for CGB was due to their refusal to participate in spite of counselling. Concerning HPVs ISH, two points should be discussed. The first was fixation more than 24 hours in UE specimens, a point that may explain the negativity for all HPVs probes even with the presence of frank HPVs in biopsies. The second was the limited number of tested probes compared to the known HPVs subtypes. Cultural sensitivity for sexual relationships in the Egyptian community in general and among women specifically, made it difficult to get detailed information even with using probing questions for assessing sexually transmitted infections.
In conclusion, this study is the first one at a national level describing the characteristics of women with cervical epithelial abnormalities. They were mostly of middle income, married, with three and more children, mostly uneducated and not working. The awareness of the Egyptian women by risk factors or symptoms of different reproductive health problems are extremely low. Prevalence of CIN and invasive lesions was 3.1% and 0.04%, while the prevalence of HPVs was 2.6% and was positive in 94.3% of cervical lesions confirming that it is the main causing agent. The study recommends introducing cacx screening for all women at least once every 10 years for women with normal cytological findings, and yearly for three successive years for inflammatory changes. CGB should be performed to all EA to avoid losing patients and subsequently tumor progression. In addition, raising awareness of Egyptian women on reproductive health and risk factors of cacx through specially designed health communication programs is mandatory.