Increased expression of HOXB2 and HOXB13 proteins is associated with HPV infection and cervical cancer progression.

BACKGROUND: Cervical cancer (CeCa) is the second most common cancer in women in developing countries, and human papilloma virus (HPV) is the primary etiological factor. Aberrant expression of HOX transcription factors has been observed in several types of cancer. To date, however, no reports exist on the expression of HOXB2 and HOXB13 proteins during neoplastic progression in CeCa and its correlation with HPV infection. MATERIALS AND METHODS: Expression of HOXB2 and HOXB13 proteins was assessed in tissue microarrays from normal cervical epithelium, cervical intraepithelial neoplasias grade 1-3, and CeCa. HPV was detected by PCR and sequencing. Expression of HOX-positive cells was determined in each diagnostic group. RESULTS: Percentage of HOXB2- and HOXB13-positive cells gradually increased from means of 10.9% and 16.7%, respectively, in samples from healthy women, to 75.2% and 88.6% in those from CeCa patients. Frequency of HPV infection also increased from 13% in healthy tissue samples to 92.3% in CeCa. Both HOXB2 and HOXB13 proteins were preferentially expressed in HPV+ samples. CONCLUSIONS: The present study represents the first report on the expression of both HOXB2 and HOXB13 proteins through cervix tumorigenesis, providing evidence that increased expression of such proteins is a common event during progression to CeCa.

Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is stimulated by therapeutic vaccination with MVA E2 recombinant vaccine.

Human papillomavirus (HPV) is the etiologic agent for cervical cancer. In Mexico, a women dies every 2 h, and since 1990 the statistics have shown that the numbers of deaths are increasing. We conducted a phase II clinical trial to evaluate the potential use of the MVA E2 recombinant vaccinia virus in treating high-grade lesions (CIN 2 and CIN 3) associated with oncogenic papillomavirus. Fifty-four female patients with high degree lesions were treated either with an MVA E2 therapeutic vaccine or with conization. Thirty-four women received the therapeutic vaccine, at a total of 10(7) virus particles per dose injected directly into the uterus once every week over a 6-week period. Twenty control patients were treated with conization. By colposcopy, 19 patients out of 34 showed no lesion, in three patients the lesions were reduced by 85-90%, in eight other lesions had reduced by 60%, and in four more patients, they were reduced by 25%. Histological analysis showed total elimination of high-grade lesions in 20 out of 34 patients after treatment with MVA E2. Eleven patients had a 50% reduction in lesion size. In two other patients, the lesion was reduced to CIN 2 and in one more patient the lesion was reduced to low grade (CIN 1). All patients developed antibodies against the MVA E2 vaccine, and generated a specific cytotoxic response against papilloma-transformed cells. DNA viral load was significantly reduced in MVA E2-treated patients. Conization eliminated the lesions in 80% of the patients, but patients did not develop cytotoxic activity specific against cancer cells and did not eliminate the papillomavirus. In addition, three patients treated with conization had recurrence of lesions 1 year later. These results show that therapeutic vaccination with MVA E2 proved to be very effective in stimulating the immune system against papillomavirus, and in generating regression of high-grade lesion.

[Bilateral ovary massive edema. Unusual gynecologic pathology. Report of 2 cases]. / Edema masivo de ovario bilateral. Patología ginecológica poco frecuente. Informe de dos casos.

We report two cases of bilateral massive ovarian edema occurred in a concentration hospital in the last five years. This condition was first described by Kalstone et al. in 1969. It may be uni or bilateral, the last one is very uncommon, until the moment of this work there have been reported only ten cases in the world literature. The main symptoms are: abdominal pain or distention, menstrual irregularity and infertility. Two features are characteristic of this pathology: 1) Fast growing in size and volume of the ovary, and 2) Abscense of neoplastic changes with extensive edema of the stroma particularly in the medulla. The current treatment is oophorectomy. In bilateral cases may be intended a conservative management with wedge resection and fixation of the ovaries to the uterus in order to prevent further torsion. We conclude that massive ovarian edema is an uncommon pathology more frequent as a cause of abdominal pain and fast growing anexial mass in young women.

Randomized placebo-controlled evaluation of intramuscular interferon beta treatment of recurrent human papillomavirus.

OBJECTIVE: To evaluate the effectiveness and safety of interferon beta in women with recurrent cervical human papillomavirus (HPV) lesions. METHODS: Women with recurrent HPV of the cervix were assigned randomly to received either 3 million IU of interferon beta daily for 5 days, followed by 2 days of rest for 3 weeks, or placebo on the same schedule (N = 61 in each group). They were evaluated at 6 and 12 months after cytology, colposcopy, and directed punch biopsy. Comparison between groups was carried out by chi(2), Fisher exact test, and Student t test, depending on the variable. Multivariable logistic regression was used to evaluate influence of variables to treatment and categorical and continuous variables were compared by Mantel-Haenszel and Wilcoxon tests. RESULTS: When treatment success rates for all patients at 6 and 12 months were compared, a highly significant statistical difference was found in the treated group compared with the placebo group [48 of 61 (79%) versus 33 of 61 (54%), P =.001, and 43 of 61 (70%) versus 26 of 61 (43%), P =.002, respectively]. Multivariable analysis showed treatment success rates with interferon beta were higher between the group with initial histopathology of cervical intraepithelial neoplasia (CIN) (odds ratio 4.86; 95% confidence interval 1.75, 13.49), and the group receiving placebo (P =.002). Side effects treatments were minimal in 70% of women; the most severe events were headaches and flulike symptoms that did not interfere with the treatment. No clinically significant changes were found in laboratory measurements of glucose or transaminases during treatment or follow-up. CONCLUSIONS: Intramuscular injections of interferon beta were effective for treating recurrent HPV lesions, particularly when associated with CIN. The only side effects were mild and controllable.