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KMID : 0350519960490010351
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Journal of Catholic Medical College
1996 Volume.49 No. 1 p.351 ~ p.364
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Integration of Human Papillomavirus 16 and 18 DNA in Cervical Cancers
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Abstract
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Cervical cancer is the most frequent malignant tumor occupying about 22% of overal female cancers in Korea. Human papillomavirus (HPV) infection is suspected as the most important etiological agent in development of cervical cancer because HPV
DNA
is
more than 90% of cervical cancers, E6 E7 transforming genes of certain HPV types are continuously expressed from them. HPV DNA is usually detected as episome in premalignant cervical lesions, thus the viral genes are intact. But, in many cervical
carcinomas, mostly it is found integrated in the host chromosome by disrupting the E2 DNA of oncogenic HPVs. The E2 protein is known to inhibit the expression of E6, E7 genes from their major promoters in vitro, and suppress the proliferation of
cervical carcinoma cells. This suggest that loss of functional E2 gene may provide selective advantage to development of cervical cancer, investigation of on the relationship between the status of E2 gene and clinical out-come of cervical cancer
may not
only help understand the mechanisms of HPV-relate cervical carcinogenesis but provide novel menagement of cervical cancer. Here, the physical status of HPV-16 and HPV-18 E2 gene in cervical was examined through molecular inethods to correlate
with
clinico-pathologic characteristics. Southern blot hybridization with mutiple enzymes digestion and HPV E2 PCR methods allowed us to differentiate between the episomal, integrated, and mixed forms of HPV-16 and -18.
1) . The 3 cervical cancers showed all episomal from of HPV DNA, and 29 integrated. The remaining 4 cancers showed mixed.
2) Of the 34 cervical cancers containing HPV-16 DNA, 31 cancer had integrated forms, of which 4 also had episomal. The two HPV-18 containing cancers had only integrated forms.
3) In 15 cervical cancers of stage IIA, 2 had episomal HPV DNA and 7 had integrated HPV DNA. In 5 cancers of stage IIB, 3 had integrated form and remaining 2 had mixed form of HPV DNA. All 7 cancers of stage III had pure form of integrated HPV
DNA.
4) In 33 Squamous cell carcinomas, 3 had episomal form, 26 had integrated, and remaning 4 had mixed from. All 3 adenocarcinomas had pure integrated forms.
5) In 16 cervical cancers with bulky tumor mass (over 4 cm size in largest diameter at the time of initial diagnosis), 1 had episomal form 13 integrated form, and remaining 2 had integrated forms, and remaining less than 4 cm size in diameter, 2
had
episomal forms, 16 had integrated forms, and remaining 2 mixed forms.
6) Among 36 cases of cervical cancers, 26 patients performed radical hysterectomy nd pelvic lymphadenectomy. In 13 deeply invaded tumor (over 10 mm), had episomal, 10 had integrated forms, and remaining 2 had mixed forms. In remaining 13 cancer
specimens, 2 had episomal, 9 had inteated form, and 2 had mixed forms.
7) Pelvic lymph nodal metastases were confirmed in 6 patients and 5 of them had integrated HPV DNA and 1 had mixed form. The remaining 20 patients were negative for pelvic metastasis and 3 had episomal, 14 had integrated forms, and 3 had mixed
forms.
In summary although, the integrity patterns of HPV DNA in cervical cancers were not statistically correlated with clinico-pathologic characteristics, the presence of pure integrated form of HPV DNA in all cases of advanced cancers,
adenocarcinoma,
and
having HPV-18 DNA suggests than such poor prognostic factors are associated with integration of HPV DNA. Therefore, more number of cervical cancers would be necessary for further study and detailed understanding of the expression of HPV
transforming
genes along with other regulatory genes may throw light on the mechanisms in the development and progression of cervical cancers.
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