Clinics and Practice 2011; volume 1:e93

Clinical response to and only one patient progressed to cervical intraepithelial neoplasia (CIN) II. The use of Correspondence: Marcelino Hernández Valencia, glycyrrhizinic acid in genital GA proved to be effective in resolving clinical Hospital General de Ecatepec Dr. José Ma. infection due to human HPV lesions. For cervical lesions with epithe - Rodríguez, ISEM y Unidad de Investigación en papillomavirus and low-grade lial changes (LSIL), treatment may be Enfermedades Endocrinas, Hospital de required for a longer period as with other Especialidades, CMN Siglo XXI, IMSS, México, squamous intraepithelial lesion D.F., Mexico. drugs used for this infection, as well as mon - E-mail: [email protected] itoring for at least 1 year according to the nat - Marcelino Hernández Valencia, ural evolution of the disease. Key words: human papilloma virus, low-grade Adia Carrillo Pacheco, squamous intraepithelial lesion, glycyrrhizinic Tomás Hernández Quijano, acid. Antonio Vargas Girón, Carlos Vargas López Introduction Received for publication: 29 September 2011. Accepted for publication: 10 October 2011. Hospital General de Ecatepec Dr. José Ma. Rodríguez, ISEM y Unidad de In recent years, human papilloma virus This work is licensed under a Creative Commons Investigación en Enfermedades (HPV) has become one of the most frequent Attribution NonCommercial 3.0 License (CC BY- Endocrinas, Hospital de Especialidades, sexually transmitted infections, producing NC 3.0). initial lesions known as genital warts. These CMN Siglo XXI, IMSS, México, D.F., may appear as small individual pimples or as ©Copyright M. Hernández Valencia et al., 2011 Mexico small, flat or raised groups and can appear Licensee PAGEPress, Italy 1,2 Clinics and Practice 2011; 1:e93 weeks or months after sexual intercourse. doi:10.4081/cp.2011.e93 Estimates of the prevalence of HPV range from 14% to 45%, and >100 viral genotypes Abstract have been reported, of which 40 can infect any mucosal body areas and are classified as Human papilloma virus (HPV) can infect high and low risk. Materials and Methods any of the mucosal areas of the body and The high-risk group is constituted by geno - cause cervical cancer. Until recently, no spe - types 16 and 18 and the low-risk group by The study design was longitudinal and cific treatments were available for this condi - genotypes 6 and 11. The latter are rarely descriptive. Women of reproductive age who tion; therefore, any damaged tissue had to be found in neoplastic lesions but cause condylo - were sexually active were included. Women removed or destroyed, which may have pre - ma acuminata. 3,4 However, it has been estab - were recruited from the outpatient gynecology sented obstetrical repercussions for some lished beyond dispute that oncogenic HPV clinic and were diagnosed with HPV on col - women. Recently, new drugs have been devel - infection represents a risk factor for the sin - poscopy with low-grade squamous epithelial oped that have shown to be effective for the gle most important development of squamous lesions (LSIL). Subjects had a history of vagi - cure of HPV infection. Glycyrrhizinic acid intraepithelial lesion. 5,6 The high incidence nal discomfort and recurrent transvaginal dis - (GA) has shown fewer side effects and its sys - and mortality due to preventable tumors has charge, without previous treatment. Treatment temic use makes it possible to reach difficult- been linked to disparities in access to care based on GA was initiated using two routes of to-treat lesions. The purpose of this study was and treatment, placing cervical cancer as the administration - systemic (oral) and topical to evaluate the clinical outcome of GA to elim - second most common cause of death in (spray) - carried out for a minimum period of inate the epithelial lesion and HPV. We car - women as well as causing enormous social 8 weeks. After being explained the reason for ried out a longitudinal, descriptive study that unrest in those women with HPV infection. 7,8 the study and treatment with GA, all patients included women of reproductive age who Primary prevention with vaccination against were asked to sign informed consent for their were diagnosed with HPV associated with HPV is often inaccessible due to its high participation. During the initial evaluation a low-grade squamous intraepithelial lesion cost. 9,10 survey was conducted and demographic data (LSIL). Subjects began treatment based on GA In addition, if left untreated, these lesions were recorded in regard to sexual behavior and using two routes of administration - systemic can have implications in regard to reproduc - reproductive health. After initiation of therapy, (oral) and topical (spray) - with assessments tion, recurrent opportunistic genital infec - all patients had colposcopy and Pap test repeat - every month to determine the clinical tions and, in extreme cases, anatomic ed each month to determine any clinical and changes of the lesions through colposcopy changes. Until recently, there were no specif - lesion changes that were recorded graphically. and Papanicolaou (Pap) smear. Simple statis - ic treatments for this condition. Damaged tis - Disposable materials were used for sampling tics were used along with two-tailed Student’s sue had to be destroyed or removed which, in and periodic reviews. Disposal of contaminat - t-test; P<0.05 was considered statistically sig - young women, could have reproductive conse - ed materials was in accordance with safety nificant before and after treatment. There quences. 11,12 Recently, however, new drugs standards for the elimination of biological and were 70 eligible patients, of whom 62 fulfilled have shown good effectiveness to cure HPV toxic waste products. 15 Treatment and follow- the inclusion criteria. Age of subjects was infection, among which is GA 13,14 that has up were carried out without interruption until 27.8±9.5 years. At the time of the study, 100% shown fewer adverse effects regarding irrita - cure was demonstrated (no HPV lesion estab - of the patients had HPV infection, 40% were tion, burns, complexity in application and lished by colposcopy and Pap smear). associated with LSIL, and only 16% used a control of dosage, as well as the possibility of Persistence of the disease was considered barrier contraceptive (condom) method. systemic use that allows treating those when there was no improvement in the lesion Resolution was achieved in all patients from 4 lesions not visible or difficult to reach and there was advancement to other stages of weeks of treatment initiation and improve - anatomically. The purpose of this study was to the LSIL. ment was achieved in the majority of patients evaluate the clinical outcome of GA on the For statistical analysis, simple statistics at 12 weeks (74%) (P<0.001). However, there elimination of intraepithelial lesions and were used with measures of central tendency was persistence of LSIL in 27.7% of patients HPV. and dispersion, and two-tailed Student’s t-test

[page 200 ] [Clinics and Practice 2011; 1:e93] Case Report to compare between-group differences of the structure in rural-area preventive programs. 16- include chemically induced cytotoxicity and changes; P < 0.05 was considered statistically 18 Understanding the natural history of HPV ablative methods such as cryotherapy, electro - significant before and after treatment. infection and the principal characteristics coagulation diathermy, thermocoagulation,

related to its evolution are among the most CO 2 laser vaporization, loop diathermy, cold important epidemiological aspects of this dis - knife conization and hysterectomy that allow ease. Information available regarding the clin - the destruction and excision of HPV-infected Results ical infection of HPV is identical to the evolu - tissue. There are topical treatments such as tion of CIN. These consist of developing latent organic acids, trichloro- and bicloracetic acid There were 70 eligible patients, of whom 62 and subclinical infections and the tendency of and antimetabolites that include 5-fluorouracil patients fulfilled the inclusion criteria. the virus to remain in a persistent state for an and antifungal agents such as podophyllin and Patients were aged 27.8±9.5 years. Obstetric extended period and then reactivate itself or podophyllotoxin. There are also therapeutic characteristics are described in Table 1. At the undergo spontaneous resolution. 19 vaccines, antivirals (acyclovir, vidarabine) time of the study, 100% of the patients present - HPV DNA has been found in 99.7% of cervi - and, finally, immunoregulators such as inter - ed with HPV infection, and 40% were associat - cal cancer cases. The clinical lesion is visible feron-alpha and imiquimod. 12,22 In relation to ed with LSIL. Only 16% were using barrier and is characterized by condylomas or genital the drug used in the current study, it is known method contraception such as a condom, warts. The subclinical lesion causes no symp - that the beneficial effect is obtained because which offers some protection for HPV; 50% did toms and is diagnosed by colposcopy or histol - GA increases the production of viral cyclin, not use any form of contraception and the ogy. Latent infection is associated with DNA of which induces the selective death of virus- remainder were distributed between mechani - HPV in tissue that has no clinical or histologi - infected cells. GA also stimulates production of cal methods and hormonal action (Table 2). cal abnormalities. Approximately 70% of interleukin-12 in macrophages, which facili - Recovery was achieved in all patients with the women with HPV infections become negative tates the development of T-helper lymphocytes use of GA, which was observed from 4 weeks of for HPV DNA determination in a year and up to in cell-mediated immune response, inhibits treatment initiation but without significant 91% at 2 years; 10% of infected women will suf - viral protein phosphorylation mediated by cel - difference. Improvement in most patients fer from persistent infections, which depends lular kinases and modifies the posttranslation - (74%) was demonstrated at 12 weeks on the immune response of the female genital al signals essential for growth. It also promotes (P<0.05), and in all patients after 13 weeks tract as part of an integral systemic response inhibition of prostaglandin E2 in damaged tis - (P<0.001) (Table 3). However, there was per - as well as on other factors such as genetic, sue, causing inflammation and increased tis - sistence of LSIL in 27.7% of patients and only environmental, nutritional, and even cultur - one patient progressed to CIN II; therefore, the al. 20 Adding to this, there is the risk of develop - usual treatment for the lesion had to be com - ing precancerous lesions and even to develop Table 1. Obstetrical characteristics of the plemented. cervical cancer. This process normally takes an patients ( n = 62). average of 15 years, offering many opportuni - Variable Mean ± SD ties for detection and treatment. 21 Along with the immune response, several Gestations 1.7±1.0 Discussion risk factors have been identified that appear to Births 1.9±0.3 be associated with the behavior of HPV, the Abortions 1.7±0.1 In most patients, partial clinical remission most important being smoking, prolonged use Cesareans 1.3±0.2 of HPV at 2 weeks of treatment initiation was of oral contraceptives, parity, sexually trans - Rhythm 30.9±8.7×4.2±1.6 observed as demonstrated by colposcopy and mitted infections, chronic inflammation and Pap test, although without statistical differ - nutritional factors as deficiency of antioxi - ence that, after 4 weeks, become significant. dants such as folate and vitamins A, C and E. Table 2. Contraceptive method used and Some cases persisted with LSIL because the It is know that, in general, simple dietary reason for no pregnancy ( n=62). drug has no specific action on these types of changes, maintaining an optimal body weight Method Frequency (%) lesions, similar to the drugs currently used to and regular physical activity may prevent up to treat HPV infection. 30% of cancers and merely changing one’s diet None 50 There were no secondary side effects with with increased fruits and vegetables could pre - Condom 16 the doses used for the required time up until vent 20% of cancers. Identification and modifi - IUD 10 clinical improvement compared with other cation of cofactors are important because they recently used drugs. This allowed better treat - can have a significant impact on modulating Oral hormones 10 ment adherence by patients because once the the persistent infection and progression of Tubal ligation 8 drug was initiated, treatment was not aban - HPV infection to neoplasia. Coitus interruptus 8 doned until a positive clinical outcome was At present there are various treatments for Injectable hormones 2 squamous intraepithelial lesions, but these achieved. In addition, this also allowed applica - Primary sterility 2 tion of a topical drug for the same patient are not effective for HPV. These treatments quickly and easily without the need for fre - quent scheduled medical visits as necessary with other drugs used for this same purpose. Table 3. HPV infection cure ( n=62). Cervical cancer has a high incidence in Weeks Frequency (%) Cumulative (%) P developing countries. Therefore, in these pre - 4 14.5 14.5 NS ventable lesions it has been observed that there are great disparities in access to care 8 27.6 42.1 NS and treatment such as inequality in regard to 12 31.9 74.0 <0.05 access to health services in low-income >13 26.0 100.0 <0.001 women as well as poor quality and poor infra - NS, non significant.

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