High-risk human papillomavirus, tumor suppressor protein p53 and mitomycin-C in invasive squamous cell carcinoma cervix.
BACKGROUND
Clinical data relating to human papillomavirus (HPV) infection and p53 status in cervical cancer has been sparse and confusing.


OBJECTIVE
To evaluate high-risk HPV and expression of tumor suppressor protein p53 in squamous cell carcinoma of cervix and to assess response to mitomycin-C in neo-adjuvant chemotherapy.


METHODS
Teaching College Hospital; Gynecologic Oncology Unit and Department of Pathology. Prospective, randomized.


METHODS
Expression of p53 protein was assessed, using immunohistochemistry with mouse monoclonal antibody in 30 consecutive patients undergoing radical hysterectomy or admitted for neo-adjuvant chemotherapy. Human papillomavirus DNA (HPV DNA) was assessed using hybrid capture II technology. Patients eligible for chemotherapy were randomized into vincristine, bleomycin and cisplatin (VBP) group and VBP with mitomycin C group.


METHODS
Chi-square test, one-way ANOVA, Pearson's correlation; Mann-Whitney, McNemar and Fischer's exact tests were used for statistical analysis.


RESULTS
All patients with cancer cervix were positive for high-risk HPV DNA having relative light units/cut off values ranging from 3.4-2389.21 (P value = 0.006). High viral load of high risk HPV DNA was seen in advanced stages (P = 0.05) and an association of viral load with tumor volume was also seen (r = 0.361, P = 0.05). Analysis of p53 protein in cervical carcinoma patient showed expression in 50% of cancer specimens (P value < 0.001). McNemar's and Fischer's exact test showed no change in p53 status post-chemotherapy; however 66% of stage II B patients in VBP-M group became operable.


CONCLUSIONS
High-risk HPV was universally present in all cases of cancer cervix and viral load was associated with stage and tumor volume while p53 protein was expressed in 50% of cases suggesting deregulation. More studies using mitomycin-C in cervical cancer treatment protocols are needed.
Rajaram
S
S
Department of Obstetrics and Gynaecology, Guru Teg Bahadur Hospital, University College of Medical Sciences, Delhi - 110 095, India. shalini_rajaram@rediffmail.com
Gupta
G
G
Agarwal
S
S
Goel
N
N
Singh
K C
KC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000821:virology*; D017024:Chemotherapy, Adjuvant; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D020360:Neoadjuvant Therapy; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000821:virology*; D014750:Vincristine / Q000008:administration & dosage; D019562:Viral Load
D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53; D001761:Bleomycin; D016685:Mitomycin; D014750:Vincristine; D002945:Cisplatin