One thousand-two hundred and twenty eight (1228) female individuals and patients presented with different gynecologic complaints were iincluding in this study. Cervical cytological examinations were performed for their Pap-smeared and-stained cervical cellular scrapes and according to their main cytological findings they were divided into 10 cytological groups, namely (1) cervical (dysplasia/neoplasia and/or HPV infection(2)atrophic vaginitis and cervicitis; (3) Squamous metaplasia;(4) endocervicitis; (5) trichomoniasis; (6) moniliasis (candidiasis); (7) histiocytes /giant cells; (8) folic acid deficiency; (9) cervicitis; and (10) healthy (no changes) groups . Among these groups, the 167 patients in the above first group, have constituted the risk group of this study. Further, this group was categorized into 3 major groups, namely (1) condylomata acuminata (including a subgroup with a typical criteria of HPV infection), (2) pre-invasive cervical neoplasia (including minimal, mild, moderate and severe dysplasia) and lastly (3) invasive cervical (adeno-and squamous I, cell) carcinoma. A group of 38 female individuals with healthy (no changes) cervices was also taken as a control group for the present study. In addition to these cytological samples, 55 formalin-fixed, paraffin-embedded archival tissue blocks that were taken from patients diagnosed to have either condylomata acjuminata (6 blocks), cancer precursors (9 blocks) (4 of them were mild, 2 of them were moderate and 3 of them were severe dysplasia) or invasive cervical (adeno-and squamous cell) carcinoma (40 blocks) were also included in this study. Further, 20 archival tissue blocks were examined as an archival control group. After a full history taking and clinical gynecological examination of all these (10) groups, the DNA isolated from a representative cytological samples of invasive cervical squamous cell carcinoma and healthy individual groups were investigated by RAPD-PCR analysis for the purpose of analysis of genomic alterations at the molecular level. The DNA isolated from the cytological samples of the risky group and its control group were subjected to SCAR-PCR analysis for the detection of HPV DNA and then these HPV DNA were further genotyped by restriction endonuclease analysis using 2 restriction enzymes, namely Tru 91 and Rsal. In addition, SCAR-PCR and restriction endonuclease analysis was used for the archival tissue blocks (patients and controls) for similar purposes. Another representative cytological samples from the group of patients with condylomata acuminata were prepared and subjected for transmission electron microscopy examination for the identification of HPV particles. The following summarized results were found: A general cytopathological and archival instopathological studies .1. The detection of samples with either typical (classic) or atypical (non-classic) cytological criteria of cervical HPV infection (i.e. condylomata acuminata) constituted 1.3% of the total number of the collected specimens (i.e. 16/1228) and 9.6% of the total risky group samples (i.e. 16/167). These patients with typical HPV cytological criteria were also associated with one grade of pre-invasive cervical neoplasia. The minimal dysplasia assopiated with 6.2%, the mild dysplasia associated with 37.5%, moderate dysplasia associated with 31.3% and severe dysplasia associated with 25% of condylomata acuminata. 2. The patients with all grades of pre-invasive cervical neoplasia constituted 7.4% (91/1228) of the total number of the patients in this study ancT54.5% (91/167) of the risky group. From this group, minimal dysplasia constituted 1.9% (23/1228) of the total samples and 13.8 (23/167) of the total risky group. Tne dysplasia group comprised 4.2% (52/1228) of the total collected samples and 31.1% (52/167) of the total risk group. Whereas, each of the moderate and severe dysplasia groups constituted 0.7% (8/1228) of the total number of the patients and 4.8% (8/167) of the risky group. 3. The distribution of koilocytosis within various grades of cervical neoplasia was found as follows: 4.3% (1/23) in minimal dysplasia; 11.5% (6/52) in mild dysplasia: 62.5% (5/8) in moderate dysplasia and 50% (4/8) in severe dysplasia. 4. The patients with invasive cervical carcinoma constituted 2.6% (32/1228) of the total patients and 19.2% (32/167) of the risky group. —. Only 2_patients (6,3%) had the diagnosis of adeno-carcinoma; whereas, the rest (93.7%) of patients diagnosed as squamous cell carcinoma. 5. Forty archival tissue blocks were obtain from patients with invasive cervical carcinoma. Of these, adeno-carcinoma constituted 17.5%, whereas squamous cell carcinoma comprised the rest (82.5.%) fbf these blocks. The grading of adenocarcinoma was found as follows: 14.3% (1/7) 'was well differentiated and another one of them was poorly differentiated, whereas the rest blocks (71.4%) were moderately differentiated. In the group of squamous cell carcinoma, moderate differentiation constituted two-thirds (22/33) of the blocks, while poor differentiation occupied the rest one third. B-Correlative - Chemical study The overall clinical presentations of the group of patients who were cytologically diagnosed as having HPV infection and/or cervical neoplasia (whether pre-invasive or invasive) were indistinguishable from all other 9 cytological groups of this study. Similarly, HPV DNA-PCR positive groups of condylomata acuminata and cervical neoplasia were clinically indistinguishable from their HPV-DNA-PCR negative counter groups. However, among many other findings related to the history and clinical examinations, an age of patients near or around the time of menopause, muliparity, vaginal bleeding (especially, inter-period or post? coital bleeding), bloody vaginal discharge, lower backache and ulceration of the cervix uteri (all the cervix or selectively anterior or posterior lip) were found significantly higher in invasive cervical carcinoma (irrespective to their state of HPV DNA-PCR positivity) than all other cytological control groups as well as all the subgroups of cervical neoplasia group in this study. C: RAPD -PCR analysis .Among forty-six different arbitrary primers of decamer (10) oligonucleotides tried for RAPD-PCR analysis, only 18 RAPD-primers produced reproducible RAPD patterns from genomic DNA isolated from the blood and cervical cellular scrapes of 2 healthy female individuals as well as 6 patients with invasive cervical sq.C.CA. Two of these patients were treated with radiotherapy before taken their samples, whereas the rest 4 patients were tested before their treatment. The following results were obtained: 1. RAPD-PCR analysis of females with healthy cervical cytology -- showed no DNA polymorphisms among the resulted DNA banding profiles of the blood and cellular samples as specified for each primer.2. RAPD-PCR analysis of untreated patients showed that all the primers used in these amplification reactions produced clear polymorhisms (in terms of intensity, number and molecular weight of produced bands) in the DNA banding profiles of blood and cellular samples. . These polymorphisms were related to the integration of oncogenic HPV genotypes in the genomic DNA of 2 patients and were confirmed by SCAR-PCR analysis for HPV DNA of these patients. RAPD-PCR analysis of the 2 patients! treated for cervical cancer showed that all primers produced no DNA polymorphisms among the resulted DNA: banding profiles of blood and cellular samples specified for each primer In the view of all these results, RAPD-PCR is possible to be used as a good tool for follow up the treatment of these patients and the detection of any genetic alterations at molecular levels. D- SGAR-PCR detection and genotyping of HPV . The results of 218 samples that were subjected to SCAR-PCR analysis and restriction endonuclease genotyping are described according to the following individual groups:. E. Condylomata acuminata Twenty-Two specimens (16 cytological and 6 archival tissue) from condylomomata acuminata as well as 16 cytological samples with atypical criteria of HPV infection were tested. Tlieir results were found as followed 62.5% and 83.3% of cytological and arcfiival tissues from these patients, respectively, were found to be HPV-DN^\-PCR positive. Six and four different HPV genotypes have been identified in the cytological and archival tissue HPV-DNA amplicons, respectively. These were HPV 18 (10%), HPV 56 (40%), HPV 35 (30%), HPV 31 (10%), HPV 16 (10%) and HPV (11) (20%) in the cytological samples and HPV 6 (20%), HPV11 (20%), HPV 16 (20%), HPV 56 (40%) in the archival tissue specimens. Among the 16 samples with atypical HPV criteria, only one (6.3%) sample was shown to have amplified HPV-DNA of-HPV 11 genotype F- Premyasive cervical neoplasia. In this group, 76 samples (67 cytological scrapes and 9 archival tissue) were tested . The overall prevalence of HPV DNA in the total cytological group that not associated with koilocytosis was 7.5% whereas in the total archival blocks was 33.3%. The prevalence of HPV DNA in the total cytological samples from preinvasive neoplasia that were associated with koilocytosis was 62.%. Regardless koilocytosis, the prevalence of HPV DNA in the total group of perinvasive neoplasia was shown to be 18.1%. Five different HPV genotypes were recognized in , cytological samples as follows HPV 18, HPV 16. HPV 31, HPV 35 and V 11. Whereas, the following 3 genotypes of HPV were identified in Issue blocks: HPV 16, HPV 35 and HPV 11.G- Invasive cervical carcinoma In this group, seventy two (72) specimens (32 cervical cellular scrapes and-40;archival tissue blocks) were; investigated of'the.presence of HPV DNA.in the total cytological group was 25% whereas in the total group of archival tissues was 20% The following different HPV genotypes were found in cellular 'specimens: HPV 16, HPV 35, HPV 56 and HPV 11 whereas 5 genotypes were recognized in tissue blocks. These are: HPV 16 ( 50%), HPV 33 and HPV 56 (each,12.5%)and HPV 35 and HPV 1 l(each ,25%). The overall results of present study show that HPV 16 and HPV 35 constitute the majority of oncogenic genotypes identified that followed by HPV 56 then HPV 33 genotypes. 4. The control group None of the DNA isolated from a t btal number of 32 specimens (12 cervical scrapes and 10 archival tissue blcjcks from healthy individuals and 10 archival tissue blocks from patientjs with chronic cervicitis) showed HPV DNA amplicons. E- Transmission electron microscopie identification of HPV Seven cytological samples from condylomata acuminata could be successfully prepared and processed for TEM. Of these, 2 sample with koilocytosis on cytology showed no viral particles by TEM. The genomic DNA isolated from the relevant cellular samples show no HPV DNA amplicons by SCAR-PCR analysis.In another one sample with koilocytosis associated with severe dysplasia/carcinoma in situ on Pap smear contained only a few numbers of virus particles. The HPV-16 genotype was detected in this sample. The remaining 4 samples with koilocytosis that associated with minimal, mild or moderate dysplasia showed large numbers of intra¬nuclear viral particles. Their genotyping revealed HPV 18, HPV-56, HPV-3 5 and HPV-3 5 plus HPV-11.