Inclusion Criteria:
* Adults aged ≥18 years.
* Clinical diagnosis of head and neck cancer (HNC), including malignancies of the oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, or salivary glands.
* Receipt of curative-intent radiotherapy to the neck, completed ≤18 months prior to randomization.
* No evidence of locoregional or distant disease recurrence, confirmed by standard-of-care imaging at 3-6 months post-RT completion as documented by the treating head and neck radiation oncologist. Participants must not be scheduled to receive additional cancerdirected systemic or radiation therapy during the study period.
* ECOG performance status ≤2.
* For women of childbearing potential (WOCBP): negative serum or urine pregnancy test within 7 days prior to randomization and agreement to use adequate contraception for the duration of study treatment and for at least 30 days following the last dose of study drug. WOCBP is defined as any female between the onset of menses and 55 years of age unless an applicable exclusionary factor is present (postmenopausal ≥12 consecutive months without menses; history of hysterectomy or bilateral salpingo-oophorectomy; history of bilateral tubal ligation or other surgical sterilization). Approved methods of contraception include hormonal contraception (oral, injectable, implantable, transdermal, or vaginal ring), intrauterine device (IUD), and barrier methods (condom plus spermicide). Periodic abstinence and the rhythm method are not acceptable. (Refer to MD Anderson Institutional Policy #CLN1114.) Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* Male participants must agree to use adequate contraception for the duration of study treatment, given the potential effects of colchicine on spermatogenesis through microtubule inhibition.
* Ability to understand and willingness to sign a written informed consent document.
Exclusion Criteria:
* Palliative or non-curative intent radiotherapy.
* Known carotid artery stenosis ≥50% at baseline screening.
* Prior history of radiotherapy to the neck (other than the qualifying course of RT for this study), carotid artery dissection, or prior carotid revascularization (endarterectomy or stenting).
* Known hypersensitivity or prior intolerance to colchicine.
* Current chronic use of colchicine for any other indication.
* Severe renal impairment (eGFR \<30 mL/min/1.73 m² by CKD-EPI equation) or end-stage renal disease requiring dialysis.
* Severe hepatic impairment (Child-Turcotte-Pugh class C).
* Pre-existing significant blood dyscrasia, defined as absolute neutrophil count \<1,500 cells/mm³ or platelet count \<50,000 cells/mm³.
* Concurrent requirement for strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, cyclosporine) or P-glycoprotein (P-gp) inhibitors that cannot be discontinued for the duration of study treatment. A list of prohibited concomitant medications is provided in Appendix A.
* History of peripheral neuritis, myositis, or clinically significant myopathy attributed to statin therapy.
* Chronic systemic corticosteroid use for any ongoing medical condition.
* Pregnancy, breastfeeding, or expressed intent to become pregnant during the study period.
* Concurrent enrollment in another clinical trial with an active interventional treatment arm.
* Psychiatric illness or social circumstances that would limit compliance with study requirements or follow-up.
* Any condition that, in the opinion of the investigator, would prevent protocol adherence or compromise participant safety
