Topical Curcumin for HPV Related Cervical Disease
Topical Curcumin for HPV Related Cervical Disease
The purpose of this study is to see if curcumin can suppress HPV infection in women with
 low-grade squamous intraepithelial lesions (LSIL) disease or treated high-grade squamous
 intraepithelial lesions (HSIL) disease. This study plans to explore the effect of curcumin as
 a potential medical treatment in HIV-uninfected and infected women with mild precancerous
 lesions of the cervix or recently treated high-grade precancerous lesions at risk for
 persistent HPV infection. About 200 women with low-grade precancerous lesions of the cervix
 or recently treated high-grade precancerous lesions will be enrolled to either insert 2000 mg
 of curcumin capsules in their vagina once a week or placebo after undergoing colposcopy or
 loop electrosurgical excision procedure (LEEP). They will have a repeat visit in 6 months
 where they will undergo a Pap smear and HPV test to determine if there are higher rates of
 HPV clearance after curcumin administration. If HPV is present or the Pap smear is abnormal,
 patients will then undergo colposcopic examination to evaluate cervical histology.
Cervical cancer is the third most common cancer worldwide. The causative agent responsible
 for cervical cancer is the persistent infection with oncogenic Human Papillomavirus (HPV).
 Rates of cervical cancer and HPV infection are increased particularly in HIV-infected women
 due to immunosuppression with cervical cancer categorized as an AIDS-defining diagnosis.
 Despite the promise of HPV vaccine in the prevention of cervical cancer, the widespread
 availability of this vaccine is limited due to cost and accessibility. Therefore, prevention
 strategies to reduce the risk of cervical cancer after HPV exposure entail treatment at the
 premalignant state, including low-grade squamous intraepithelial lesions (LSIL) and
 high-grade squamous intraepithelial lesions (HSIL), along with the eradication of HPV
 infection. There is a desperate need for an inexpensive, non-invasive alternative method to
 treat these premalignant cervical lesions and potentially suppress HPV infection.

 Curcumin, an extract from turmeric, a popular culinary spice, has been used in traditional
 Indian medicine for its anti-inflammatory and anti-infectious properties. Recent studies have
 shown the potential effect of curcumin to reduce tumors and precancerous lesions in animal
 and human cancer cells. It is postulated that curcumin achieves its effect on cancer cells by
 modulating different cellular pathways as well as altering HPV effect on tissue cells.

 The purpose of this study is to see if curcumin can suppress HPV infection in women with LSIL
 disease or treated HSIL disease. The researchers plan to explore the effect of curcumin as a
 potential medical treatment in HIV-uninfected and infected women with mild precancerous
 lesions of the cervix or recently treated high-grade precancerous lesions at risk for
 persistent HPV infection. About 200 women with low-grade precancerous lesions of the cervix
 or recently treated high-grade precancerous lesions will be enrolled to either insert 2000 mg
 of curcumin capsules in their vagina once a week or placebo after undergoing colposcopy or
 LEEP. They will have a repeat visit in 6 months where they will undergo a Pap smear and HPV
 test to determine if there are higher rates of HPV clearance after curcumin administration.
 If HPV is present or the Pap smear is abnormal, patients will then undergo colposcopic
 examination to evaluate cervical histology.
Inclusion Criteria:

 -  HIV-uninfected and infected women (without current AIDS-defining illness)

 -  Presence of a cervix

 -  Biopsy-proven LSIL disease or recently treated HSIL disease

 -  Adherence to combined anti-retrovirals (cART) if HIV infected

 -  On continuous antiretrovirals with a cluster of differentiation 4 (CD4) count >200
 cells/ml with sustained undetectable viral load for at least 3 months (only for
 HIV-positive participants)

 -  On reliable birth control: combined oral contraceptive pills (OCP), long-acting
 reversible contraception (LARC), bilateral tubal ligation (BTL) or Depo-Provera (birth
 control shot)

 -  Willing to conform to the study requirements

 -  Reliable follow-up and contact information

 -  No risk factors for HSIL or microinvasive disease (no colposcopic features of
 microinvasion, adequate colposcopy and negative endocervical curettage)

 -  For women with HSIL only, LEEP completed within 6 weeks preceding initial encounter
 with study staff and adequate wound healing

 Exclusion Criteria:

 -  Untreated HSIL or invasive features on colposcopy and the biopsy specimen

 -  Not adherent to anti-retroviral therapy (cART) (HIV infected participants)

 -  CD4 count =<200 cells/ml and detectable viral load within the last 3 months (only for
 HIV-positive participants)

 -  Lactating and pregnant people

 -  Patient with irregular cycles (more than once a month)

 -  Not on reliable birth control.

 -  Previous hysterectomy

 -  Prior diagnosis of cervical cancer, treated or untreated

 -  Inability to provide informed consent

 -  Medical condition that interferes with the conduct of the study in the investigator's
 opinion

 -  Evidence of active cervical infection or serious cervical disease necessitating
 surgery

 -  Known bleeding diathesis