Treatment Of Anogenital Warts Research Articles

Cellular Distribution and Ultrastructural Changes in HaCaT Cells, Induced by Podophyllotoxin and Its Novel Fluorescent Derivative, Supported by the Molecular Docking Studies.

Podophyllotoxin (PPT) is an active pharmaceutical ingredient (API) with established antitumor potential. However, due to its systemic toxicity, its use is restricted to topical treatment of anogenital warts. Less toxic PPT derivatives (e.g., etoposide and teniposide) are used intravenously as anticancer agents. PPT has been exploited as a scaffold of new potential therapeutic agents; however, fewer studies have been conducted on the parent molecule than on its derivatives. We have undertaken a study of ultrastructural changes induced by PPT on HaCaT keratinocytes. We have also tracked the intracellular localization of PPT using its fluorescent derivative (PPT-FL). Moreover, we performed molecular docking of both PPT and PPT-FL to compare their affinity to various binding sites of tubulin. Using the Presto blue viability assay, we established working concentrations of PPT in HaCaT cells. Subsequently, we have used selected concentrations to determine PPT effects at the ultrastructural level. Dynamics of PPT distribution by confocal microscopy was performed using PPT-FL. Molecular docking calculations were conducted using Glide. PPT induces a time-dependent cytotoxic effect on HaCaT cells. Within 24 h, we observed the elongation of cytoplasmic processes, formation of cytoplasmic vacuoles, progressive ER stress, and shortening of the mitochondrial long axis. After 48 h, we noticed disintegration of the cell membrane, progressive vacuolization, apoptotic/necrotic vesicles, and a change in the cell nucleus's appearance. PPT-FL was detected within HaCaT cells after ~10 min of incubation and remained within cells in the following measurements. Molecular docking confirmed the formation of a stable complex between tubulin and both PPT and PPT-FL. However, it was formed at different binding sites. PPT is highly toxic to normal human keratinocytes, even at low concentrations. It promptly enters the cells, probably via endocytosis. At lower concentrations, PPT causes disruptions in both ER and mitochondria, while at higher concentrations, it leads to massive vacuolization with subsequent cell death. The novel derivative of PPT, PPT-FL, forms a stable complex with tubulin, and therefore, it is a useful tracker of intracellular PPT binding and trafficking.

Microneedling-Assisted Topical Bleomycin versus Cryotherapy in the Treatment of Anogenital Warts

Microneedling-Assisted Topical Bleomycin versus Cryotherapy in the Treatment of Anogenital Warts

Effectiveness and safety of tuberculin purified protein derivative for the treatment of anogenital warts in patients with human immunodeficiency virus

Individuals with human immunodeficiency virus (HIV) infection are prone to developing persistent and unremitting anogenital warts (AGWs). To address this health condition, immunotherapy using tuberculin purified protein derivative (PPD) has been proven to be a promising novel and safe treatment for AGWs in HIV patients. Therefore, this study involved a case of a 21-year-old man with stage I HIV infection, possessing CD4 counts 548 cells/uL and routinely receiving HIV antiretroviral. Patients presented with a condyloma acuminata type AGWs, supported by histopathological results, and tested positive for Human papillomavirus type 11. The treatment approach involved administering 15 tuberculin units of PPD weekly to the largest lesion for 5 weeks. The lesion started to respond two weeks following the first injection and showed a 50% decrease in size after five weeks. There was pain on the site of injection and sub-febrile for a short period. In conclusion, tuberculin PPD is safe and has the potential for the treatment of AGWs in HIV-positive patients for further development.

Efficacy of Human Papillomavirus Vaccines for Recalcitrant Anogenital and Oral Warts

Human papillomavirus (HPV) vaccines are preventive measures to decrease HPV infection rates. Knowledge of their efficacy as treatment options for anogenital warts (AGWs) and oral warts (OWs) is limited. To evaluate the efficacy of HPV vaccinations in recalcitrant AGWs and OWs (lesions persisting more than 6 months despite conventional treatments), we compared a group of patients treated with standard therapies plus an HPV vaccine with a group of patients treated with standard therapies only. The response to treatment (in terms of the number of lesions) in the two groups was compared. Data were analyzed with the χ2 test and p values < 0.05 were considered to be statistically significant. The study included 14 patients (group A = cases) who received 3 doses of an intramuscular HPV vaccine (Gardasil 4 or Gardasil 9) in addition to the standard treatments for AGWs and OWs, and 15 age- and sex-matched patients (group B = controls) with an analogous number of lesions to group A who received only standard therapies. After 12 months, 85% of patients of group A versus 33% of group B had positive clinical outcomes (0.004). Our findings suggest a possible therapeutic role of HPV vaccines in addition to standard treatments for AGWs/OWs. Preventive vaccines, blocking the viral entry through the induction of L1-specific antibodies, can prevent autologous reinfections (through auto-inoculation) and favor the elimination of the virus.

Intralesional bivalent and quadrivalent human papillomavirus vaccines didn't significantly enhance the response of multiple anogenital warts when co-administered with intralesional Candida antigen immunotherapy. A randomized controlled trial.

Treatment of anogenital warts (AGWs) is challenging. Candida antigen immunotherapy has been proven to be a safe and relatively effective therapeutic modality; nevertheless, some patients may experience a partial or no response. Combining Candida antigen with other immunotherapies has been proposed to improve the cure rate. Immunotherapy with human papillomavirus (HPV) vaccines has been tried with conflicting outcomes. This study aimedto assess the efficacy and safety of intralesional Candida antigen, either alone or in combination with intralesional bivalent or quadrivalent HPV vaccines, for treating multiple AGWs. Eighty patients with multiple AGWs were included and randomly assigned to four equal groups: group A treated with intralesional Candida antigen only; group B treated with intralesional bivalent HPV vaccine (Cervarix) and Candida; group C treated with intralesional quadrivalent HPV vaccine (Gardasil) and Candida; and group D (control) treated with intralesional saline. Complete clearance of lesions was detected in 40%, 20%, and 60% of patients in Candida monotherapy, Cervarix/Candida, and Gardasil/Candida groups, respectively, whereas 40%, 60%, and 20% of patients in the three groups, respectively, showed partial response. Only 10% of the control group had a partial response. Therapeutic outcomes were significantly better in the three treatment groups compared to the control group, with no statistically significant difference between the Candida monotherapy group and the combination groups, but the response was significantly better in the Gardasil/Candida group than in the Cervarix/Candida group. No statistically significant difference was found between the studied groups regarding the development of side effects. Moreover, no recurrence was detected in any of the groups throughout the 3-month follow-up period. Based on our results,combining intralesional HPV vaccines with Candida antigen immunotherapy may haveno significant benefit for treating multiple AGWs. Candida antigen may be recommended as a relatively effective and inexpensive therapeutic modality. The combination of Gardasil and Candida was also effective but very expensive. The results of the Cervarix/Candida combination were unsatisfactory. This clinical trial was registered and approved prospectively by the ethical review board at Faculty of Medicine, Zagazig University.

Treatment of Pediatric Anogenital Warts in the Era of HPV-Vaccine: A Literature Review.

Anogenital warts (AWs) represent a therapeutic challenge, especially in infants, due to sensitive skin and frequent disease recurrence. Though the initial wait-and-see approach is often adopted in asymptomatic immunocompetent children, with spontaneous clearing in almost 90% of cases within two years, persistent or symptomatic lesions can be reasonably treated. However, few studies have been conducted on children. Consequently, most treatments on patients under age 12 are not approved by the Food and Drug Administration. Herein, we review possible therapies for pediatric use in AW and report an illustrative case of a two-year-old boy with atopic skin and symptomatic, persistent AWs who was successfully treated with topical podophyllotoxin, without adverse effects or recurrence. Among available therapies for AWs, topical therapies, such as immunomodulating-agents (topical imiquimod 5% and 3.75% cream, sinecatechins 15% ointment) and cytotoxic agents (podophyllotoxin and cidofovir) are considered manageable in children because of their low aggressiveness. In particular, podofillotoxin gel 5% and imiquimod 5% cream have been reported to be safe and efficacious in children. Currently, HPV vaccination is not recommended as a treatment for established HPV infection and AWs, yet a possible therapeutic role of HPV vaccination was recently suggested in the literature and deserves mention.

Cryotherapy alone versus cryotherapy followed by intralesional vitamin D3 in treatment of anogenital warts: a randomized comparative clinical study

Cryotherapy alone versus cryotherapy followed by intralesional vitamin D3 in treatment of anogenital warts: a randomized comparative clinical study

Intralesional bivalent human papilloma virus vaccine as a treatment for anogenital warts versus topical podophyllin resin 25%: A pilot study.

A role of human papilloma virus (HPV) vaccines as a therapy for genital warts was suggested, nevertheless; it has not been established in clinical trials and has yet to be determined. The objective of this study is to evaluate a potential benefit of intralesional injection of bivalent HPV (Cervarix) vaccine as a treatment for anogenital warts versus topical podophyllin resin 25%. Forty-four patients with anogenital warts were included in the study, 22 patients received intralesional Cervarix every 2 weeks until clearance of lesions or for a maximum of five sessions. The other 22 patients received topical podophyllin resin 25% twice weekly until complete resolution or for a maximum of 4 weeks. Follow up was done for 6months. Dermatology life quality index (DLQI) was measured. Complete clearance of warts was achieved in 10 patients (45.5%) in Cervarix group versus six patients (27.3%) in Podophyllin group. The difference was statistically insignificant. No recurrence of warts was reported in Cervarix group while two patients (33.3%) showed recurrence in Podophyllin group. Both treatments were well tolerated. All patients reported significant improvement of their DLQI. Intralesional Cervarix is a promising modality showing higher rates of complete response, high safety, and no recurrence.

5-Fluorouracil 0.5%/salicylic acid 10% solution in the treatment of ano-genital warts.

Different therapeutic modalities for ano-genital warts (AGWs) are available but data on the efficacy of 5-fluorouracil 0.5%/salicylic acid 10% solution (5FU/SAsol) in the treatment of AGWs are scarse. We enrolled 17 patients with AGWs (14 males, 3 females with a mean age of 34.2 years) who gave written informed consent to the off-label use of topical 5FU/Sasol. Response to treatment was assessed based on the AGWs number: complete if there was complete clearance of the lesions; partial if there was >50% decrease in the lesion number and none if there was <50% decrease in the lesion number. Considering together partial and complete treatment response, 88% of the patients at 3 months and 94% at 6 months benefited from the 5FU/SAsol treatment. 5FU/SAsol was well tolerated by all the patients except one who experienced a burning sensation immediately after the application. The clearance rate that we found for 5-FU/SAsol after 3 months of treatment is comparable with that of the other commonly used therapeutic modalities (liquid nitrogen cryotherapy, imiquimod 5% cream). However, several patients on imiquimod and almost who underwent cryotherapy reported pain as adverse event while a mild pain was rarely reported with 5-FU/Sasol. In conclusion, although nowadays in Italy 5-FU/SAsol is marketed only for the treatment of actinic keratosis, our study described its effectiveness and tolerability also in the treatment of AGWs. Our data suggest that 5-FU/SAsol should be considered not only in case of resistant/recurrent AGWs but also as the first therapeutic option, especially when the number of lesions is small.

Effectiveness of Topical 100% Trichloroacetic Acid in Treatment of Anogenital Warts in Male Patients

Introduction: Anogenital warts are benign proliferation of skin and mucosa that result from different types of human papilloma viruses (HPVS). Treatment of AGW is aimed at relieving the patient physical and psychological discomfort and preventing the spread of infection by autoinoculation. There is evidence that localized topical application of trichloroacetic acid (100 %) is effective against AGW but due to differences in skin types and possible differences in papilloma virus’s types, it was necessary to confirm its effectiveness in Pakistani Population.

Novel podophyllotoxin and benzothiazole derivative induces transitional morphological and functional changes in HaCaT cells

Podophyllotoxin (PPT) is an antimitotic drug used topically in the treatment of anogenital warts. Due to its toxicity it cannot be administered systemically as an anticancer agent. However, modified PPT derivatives such as etoposide and teniposide are used clinically as systemic agents. Thus, we invented novel PPT derivative KL3 that was synthesized by photocyclization. Earlier we have shown that KL3 has an anticancer effect in various cell lines. Here we compared the toxicity of KL3 vs PPT on non-cancerous normal human keratinocytes (HaCaT) and peripheral blood mononuclear cells (PBMC) showing that KL3 is less toxic than PPT to non-cancerous cells. At concentrations that neither induced cell death, nor affected cell cycle, KL3 in HaCaT cells evoked transient ultrastructural features of ER stress, swelling of mitochondria and elongation of cytoplasmic processes. Those changes partially reversed with prolonged incubation while features of autophagy were induced. PPT in equivalent concentrations induced HaCaT cell death by cell cycle arrest, intrinsic apoptosis and finally disintegration of cell membranes followed by secondary necrosis. In conclusion, we show that the KL3 derivative of PPT in contrast to PPT allows repair of normal keratinocytes and triggers mechanisms that restore non-tumor cell homeostasis

Cryotherapy plus low-dose oral isotretinoin vs cryotherapy only for the treatment of anogenital warts: a randomized clinical trial.

Anogenital warts are a common human papillomavirus infection. They cause emotional distress, especially when they are in the anogenital region. Cryotherapy is a first-line treatment. Previous clinical trials and case series have reported variable results with retinoids (isotretinoin) as adjuvant therapy. To determine the safety and efficacy of low-dose oral isotretinoin as adjuvant treatment of anogenital warts. Forty-six patients with anogenital warts were randomly assigned to isotretinoin + cryotherapy (n = 23) or only cryotherapy (n = 23). Patients were allocated via an interactive web-based randomization system. Evaluators were blinded to treatments. Isotretinoin 20mg/daily + cryotherapy or cryotherapy were prescribed for 6weeks. Patients were followed for 4months. Genotyping of lesions was performed before treatment started. Dermatology Life Quality Index (DLQI) and Columbia-Suicide Severity Rating Scale (C-SSRS) were measured at the beginning and end of therapy. All patients completed the study. Both Groups had 50% clearance at the end of treatment. Recurrence in the combined group was not significantly lower than in the cryotherapy group (P = 0.59). Improvement was observed in the DLQI of all patients in both groups (P = 0.001). No suicidal intention was detected with the C-SSRS. Two patients (one in each group) had liver function test abnormalities after treatment. Combined therapy showed a slight not significant efficacy for anogenital warts in Hispanic patients. Low-dose isotretinoin seems to be safe even when it is used with cryotherapy on anogenital warts. On April 25, 2019 with registration number DE19-00004, CONBIOÉTICA-19-CEI-001-20160404. Prospectively registered.

Betaglucan 0.2% versus Imiquimod 5% in the Treatment of Ano Genital Warts (Agw) Randomized Triple Blind Study 102 Patients Aged 18 to 50 Years Old in Managua, Nicaragua, Period June to September 2019 "(Preliminary Report- Due to the COVID 19 Epidemic the Cclinical Trial was stopped on August 2019. Registered in ClinicalTrials.gov with NCT 03901690 and included in the Clinical

Betaglucan 0.2% versus Imiquimod 5% in the Treatment of Ano Genital Warts (Agw) Randomized Triple Blind Study 102 Patients Aged 18 to 50 Years Old in Managua, Nicaragua, Period June to September 2019 "(Preliminary Report- Due to the COVID 19 Epidemic the Cclinical Trial was stopped on August 2019. Registered in ClinicalTrials.gov with NCT 03901690 and included in the Clinical

Intralesional immunotherapy for the treatment of anogenital warts in pediatric population

Background The prevalence of anogenital warts is increasing in adults as well as in pediatric population. The treatment of anogenital warts is challenging, particularly in children as most conventional modalities are painful and associated with high recurrence rates. Objectives To evaluate the efficacy and safety of intralesional immunotherapy for the treatment of anogenital warts in pediatric patients. Methods Forty child presenting with multiple anogenital warts were randomly assigned into 3 groups. The first group (15 patients) received intralesional MMR vaccine, the second group (15 patients) received intralesional Candida antigen and the third group (10 patients) received intralesional saline as a control. Each modality was injected into the largest wart at 2-week intervals until complete clearance or for a maximum of 5 sessions. Results Highly significant difference was found between the therapeutic response of anogenital warts to both MMR vaccine and Candida antigen compared to intralesional saline (p = .005). No significant difference was observed between MMR vaccine and Candida antigen groups (p = .885). Side effects were mild and no recurrence was detected in the 6 month follow-up period. Conclusions Intralesional immunotherapy is a promising effective and well-tolerated treatment modality for multiple anogenital warts in children.

A Multicentre, Randomised Clinical Trial to Compare a Topical Nitrizinc® Complex Solution Versus Cryotherapy for the Treatment of Anogenital Warts.

IntroductionAnogenital warts (AGW) are a relevant clinical issue in the field of sexually transmitted disease, and to date no treatment provides a satisfactory clearance rate. Treatment can be both medical and surgical, and be provided by a healthcare provider or by the patient. Cryotherapy (CRYO) is among the most common treatments for AGW. Nitrizinc® Complex solution (NZCS) is a solution containing organic acids, nitric acid and zinc and copper salts that is applied topically to warts, producing mummification of the damaged tissue. It is considered to be an effective and well-tolerated treatment for genital and common warts. The aim of our study was to compare NZCS to CRYO in the treatment of AGW.MethodsWe performed a prospective, multicentre, single-blind, randomised, superiority clinical study involving 120 patients, aged 18–55 years, diagnosed with a first episode of AGW, with each patient having from three to ten AGW. The patients were treated either with NZCS or CRYO for a maximum of four treatments. Primary endpoints were: (1) comparison of the clinical efficacy of CRYO and NZCS, based on response to treatment (clearance of AGW) within four treatment sessions; and (2) tolerability, assessed via a short questionnaire at the end of each treatment session. Secondary endpoints were: (1) number of treatments needed for clearance; and (2) recurrence at 1 and 3e months after confirmed clearance. The results were analysed on an intention-to-treat basis.ResultsA complete response was achieved in 89.7% of the NZCS group and in 75.4% of the CRYO group (p = 0.0443). NZCS was found to be better tolerated. There was no difference between the NZCS and CRYO treatment arms in the number of sessions needed to clear the lesions. Recurrence occurred after 1 month in 18.4% of the NZCS group and 38.1% of the CRYO group (p = 0.0356), and after 3 months in 25 and 40.6% of these groups, respectively (p = 0.1479).ConclusionsNitrizinc® Complex solution can be considered to be as effective as CRYO for the treatment of small (< 5 mm) external AGW, with a better tolerability profile and lower rate of recurrence.Trial RegistrationISRCTN identifier, ISRCTN36102369.

Randomised controlled trial of 1% and 5% 5-fluorouracil creams compared with 90% trichloroacetic acid solution for anogenital wart treatment.

To evaluate the efficacy and safety of 1% and 5% 5-fluorouracil (5-FU) creams compared with 90% trichloroacetic acid (TCA) for the treatment of anogenital warts. we conducted a randomised controlled study in 72 subjects allocated to three groups: 1% 5-FU, 90% TCA and 5% 5-FU; 90% TCA was administered once a week, whereas 5-FU cream was applied three times a week. Response to therapy and side-effects were evaluated weekly for seven weeks. Evaluation at week 7 demonstrated that there was no significant difference in the efficacy between 1% 5-FU cream and 90% TCA (p = 0.763) or between 5% 5-FU cream and 90% TCA (p = 0.274). Subjective side-effects with 1% 5-FU were significantly milder than 90% TCA; however, significantly milder objective side-effects were observed only at weeks 2, 6 and 7. The subjective side-effects with 5% 5-FU were also significantly milder than 90% TCA; however, significantly milder objective side-effects were observed only at week 2. 5-FU may become an alternative topical therapy as it offers the benefit of self-application; furthermore, a concentration of 1% 5-FU cream is recommended due to milder side-effects.

Could the human papillomavirus vaccine prevent recurrence of ano-genital warts?: a systematic review and meta-analysis

Human papillomavirus (HPV) is the most prevalent sexually transmitted infection worldwide and ano-genital warts (AGWs) are highly infectious. This virus is transmitted through sexual, anal, or oral contact as well as skin-to-skin contacts. Treatment for this condition has significant morbidity and it can be frustrating in certain cases. The HPV vaccination has been demonstrated as a promising strategy of secondary prevention in HPV-related diseases such as head and neck cancers, cervical diseases, and recurrent respiratory papillomatosis. Regarding AGWs, it is unclear whether vaccination can provide analogous clinical benefit. The aim of this work is to systematically review the literature regarding HPV vaccination for secondary disease prevention after treatment of AGWs. From October to December 2018, a systematic search for clinical trials was conducted in five databases: PubMed, MEDLINE, EMBASE, Cochrane, and clinicaltrials.gov using a combination of the following descriptors: 'gardasil' OR 'cervarix' OR 'nine-valent' OR '9-valent' OR 'vaccine' AND 'recurrence' OR 'relapse' AND 'hpv' OR 'papillomavirus' AND 'warts' OR 'condyloma.' Data were synthetized and entered in the Review Manager software (RevMan 5.3.5) to perform the meta-analysis. The search yielded 824 potentially relevant studies. Two studies fulfilled the eligibility criteria involving 656 participants. The meta-analysis estimated the rate of recurrence of AGWs was similar between the vaccine group and the control group. The overall effect estimate was 1.02 (0.75-1.38). This is the first meta-analysis exploring the effect of HPV vaccine in preventing the relapse of AGWs. These results suggest that HPV vaccination does not provide secondary benefit in patients with previous AGWs. However, these results cannot be generalized due to the scarce number of RCTs currently available in the literature. The outcomes from future randomized controlled trials (RCTs) are warranted to further clarify the precise effect of the vaccine.

Local Management of Anogenital Warts in Non-Immunocompromised Adults: A Network Meta-Analysis of Randomized Controlled Trials.

IntroductionNo hierarchy of first-line treatments for anogenital warts (AGWs) is provided in international guidelines. This study aimed to determine the efficacy of topical treatments and ablative procedures for the management of AGWs.MethodsTwelve electronic databases were systematically searched from inception to August 2018. All randomized controlled trials (RCTs) comparing immunocompetent adults with AGWs who received at least 1 provider-administered or patient-administered treatment in at least 1 parallel group were included. Risk of bias assessment followed the Cochrane Handbook. The study endpoint was complete lesion response after clearance and recurrence assessment. A network meta-analysis was performed.ResultsA network geometry was constructed based on 49 of the 70 RCTs included in our systematic review. All but 4 RCTs had a high risk of bias. The most efficacious treatments compared to placebo were surgery (RR 10.54; CI 95% 4.53–24.52), ablative therapy + imiquimod (RR 7.52; CI 95% 4.53–24.52), and electrosurgery (RR 7.10; CI 95% 3.47–14.53). SUCRA values confirmed the superiority of surgery (90.9%), ablative therapy + imiquimod (79.8%), and electrosurgery (77.1%). The most efficacious patient-administered treatments were podophyllotoxin 0.5% solution (63.5%) and podophyllotoxin 0.5% cream (62.2%).ConclusionsWith low-level evidence of most included RCTs, surgery and electrosurgery were superior to other treatments after clearance and recurrence assessment. Podophyllotoxin 0.5% was the most efficacious patient-administered treatment. Combined therapies should be evaluated in future RCTs in view of their identified effectiveness. The results of future RCTs should systematically include clinical type, number and location of AGWs, and sex of the patient, to refine therapeutic indications.Protocol RegistrationPROSPERO-CRD42015025827Electronic supplementary materialThe online version of this article (10.1007/s13555-020-00357-z) contains supplementary material, which is available to authorized users.

Association Between Fetal Safety Outcomes and Exposure to Local Podophyllotoxin During Pregnancy

Podophyllotoxin is an antimitotic agent primarily used in the local treatment of anogenital warts. Data that enable the assessment of the fetal safety of podophyllotoxin use during pregnancy are lacking. To investigate the association between local podophyllotoxin exposure during pregnancy and risk of adverse fetal outcomes. This cohort study obtained individual-level pregnancy data from various nationwide registries in Denmark from the study period of January 1, 1997, through December 31, 2016, resulting in a cohort of 1 650 649 pregnancies. Pregnancies with multiple records on overlapping dates and pregnancy records with implausible or missing information on gestational age were excluded. Local podophyllotoxin-exposed pregnancies were compared with unexposed pregnancies and matched in a 1:10 ratio according to propensity scores on a wide set of baseline characteristics. Five distinct study cohorts were constructed, one for each outcome analysis. Sensitivity analyses included a comparison of podophyllotoxin-exposed pregnancies with pregnancies with podophyllotoxin use only before pregnancy onset. Data analyses were performed from April 27, 2019, to June 26, 2019. Filled prescription for local podophyllotoxin. Primary outcomes were major birth defects and spontaneous abortions. Secondary outcomes were preterm births, small-for-gestational-age (SGA) size, and stillbirths. Logistic regression was used to estimate the prevalence odds ratios (ORs) of major birth defects, preterm births, and SGA size, and Cox proportional hazards regression modeling was used to estimate hazard ratios (HRs) of spontaneous abortions and stillbirths. This study included 9229 pregnancies (mean [SD] maternal age at pregnancy onset, 27.7 [5.2] years) for the analyses of major birth defects and 18 590 pregnancies (mean [SD] maternal age at pregnancy onset, 26.4 [6.0] years) for the analyses of spontaneous abortions. Among the podophyllotoxin-exposed pregnancies, 29 infants (3.5%) were diagnosed with major birth defects, compared with 286 (3.4%) among the unexposed pregnancies. A total of 141 podophyllotoxin-exposed pregnancies (8.3%) ended in spontaneous abortion, compared with 1626 (9.6%) among the unexposed pregnancies. No statistically significant associations were found between podophyllotoxin exposure during pregnancy and major birth defects (prevalence odds ratio [OR], 1.02 95% CI, 0.69-1.50), spontaneous abortions (HR, 0.87; 95% CI, 0.73-1.04), preterm births (prevalence OR, 1.08; 95% CI, 0.86-1.35), SGA size (prevalence OR, 1.01; 95% CI, 0.85-1.22), or stillbirths (HR, 0.58; 95% CI, 0.18-1.86). Sensitivity analyses of the primary outcomes achieved similar results. Findings from this study suggest that podophyllotoxin use during pregnancy may be safe, as it did not appear to be associated with an increased risk of adverse fetal outcomes. These findings may help guide clinicians, patients, and drug regulatory authorities when prescribing podophyllotoxin.

Efficacy and safety of treating anogenital warts with intralesional vitamin D3 injection: a report on 20 Egyptian patients

Background Anogenital warts (AGWs) are always resistant to traditional treatment options. Recently, vitamin D3 injection have proven its efficacy in the treatment of extragenital warts. To the best of our knowledge, there are no studies on using intralesional vitamin D3 in the treatment of genital warts. Aim To evaluate the efficacy of intralesional vitamin D3 injection in the treatment of AGWs. Patients and methods Twenty patients with AGWs were included in this study. Vitamin D3 (7.5 mg/ml) was injected into the base of the warts every 2 weeks for 2 months. Results Only two (11.11%) patients showed complete resolution; six (33.33%) patients showed moderate response, while 10 (55.55%) patients showed mild response. Recurrence has been obtained in moderate and mild responders; no adverse effects were observed. Conclusion The efficacy of using intralesional vitamin D3 in the treatment of AGWs is not as effective as its role in extragenital warts.