Method of treating cervical neoplasia in patients infected with human papilloma virus
The invention generally features compositions and methods for the diagnosis, treatment, and monitoring of neoplasia in a subject, as well as methods of treatment selection.
1. A method for treating cervical neoplasia in a subject infected with human papilloma virus (HPV), the method comprising:
(a) detecting an HPV status from a cervical sample obtained from the subject, wherein the HPV is HPV type 6, 11, 16, 18, 31, 33, and/or 51;
(b) measuring a level of a CXCL12 polypeptide having a molecular weight greater than about 10 kD or 11 kD in a cervical neoplasia sample of the subject;
(c) comparing the level of the CXCL12 polypeptide in the cervical neoplasia sample of the subject to a first reference level and a second reference level; and
(d) administering a less aggressive treatment to the subject identified as having a pre-invasive cervical neoplasia, wherein the pre-invasive cervical neoplasia comprises a level in the cervical neoplasia sample above the first reference level and below the second reference level, or administering a more aggressive treatment to the subject identified as having an invasive stage of cervical neoplasia, wherein the invasive stage of cervical neoplasia comprises a level in the cervical neoplasia sample above both the first reference level and the second reference level,
wherein the first reference level is an increase of less than about 3-fold compared to a control sample;
wherein the second reference level is an increase of more than 3-fold compared to the control sample;
wherein the less aggressive treatment regimen is selected from the group consisting of loop electrical excision procedure (LEEP), trachelectomy, and hormonal therapy; and
wherein the more aggressive treatment regimen is selected from the group consisting of hysterectomy, radiation therapy, and chemotherapy;
thereby treating the cervical neoplasia in the subject.
2. The method of claim 1 , wherein the HPV status is cervical intraepithelial neoplasia-2 (CIN2).
3. The method of claim 1 , wherein the second reference level is an increase of higher than 5-fold compared to the control sample.
4. The method of claim 1 , wherein the increased level of CXCL12 polypeptide indicates an increased clinical aggressiveness of the cervical neoplasia.
5. The method of claim 1 , wherein the method further involves detecting CD3-expressing T cells.
6. The method of claim 1 , wherein the first reference level or the second reference level is the level of CXCL12 present in the control sample.
7. The method of claim 1 , wherein the first reference level or the second reference level is derived from a healthy control subject.
8. The method of claim 1 , wherein the increase in the level of CXCL12 identifies a propensity for the cervical neoplasia to develop into an invasive cervical carcinoma.
9. The method of claim 1 , wherein CXCL12 molecular weight is determined in an immunoassay, in an SDS-PAGE assay, by mass spectroscopy, by Western blot, or ELISA.
10. The method of claim 1 , wherein the CXCL12 polypeptide selectively binds a CXCL12-specific antibody.
11. The method of claim 1 , wherein the CXCL12 polypeptide has at least about 85% identity to the amino acid sequence of any of SEQ ID NOs: 2-7.
12. The method of claim 1 , wherein the control sample is from a healthy control subject.
13. The method of claim 1 , wherein the control sample is from a sample obtained from the subject prior to treatment.
14. The method of claim 1 , wherein the HPV status is cervical intraepithelial neoplasia-3 (CIN3).
15. The method of claim 1 , wherein the HPV status is invasive squamous cell carcinoma (INV, SCC).