1.  Also known as condylomata acuminata or venereal warts, is one of the most common types of sexually transmitted infection and primarily affect younger people.  The disease usually is caused by HPV genotypes 6 or 11, which normally are not involved with cancers but can cause abnormal pap smear.  In 8 to 14%, the person has been infected with more than one type of HPV

2.  50 to 80 percent of sexually active women are infected at least once in their lifetime. Transient or undetectable  Women under 25 to 30 years have higher rates of infection although a second peak has been described in postmenopausal women.

3.  Association with HPV genotypes 16 and 18 can give rise to subclinical lesions associated with CIN and squamous cancer.  Approximately 1 million cases of genital warts occur each year in the United States and an estimated 32 million cases occur worldwide.

4.  In women, genital warts can appear on the vulva, the walls of the vagina, the perianal area, and the cervix. May increase in size during pregnancy.  In men, they may be found on the tip or shaft of the penis, the scrotum, or the anus.

5.  In neonates, respiratory & laryngeal papillomatosis follows NVD but can occur after C/S. Typically presents between 2 & 3 years of age and extends into adolescence.  About 37% of laryngeal papillomatosis become malignant.  Occurs more commonly in first-born children and in the children of young mothers who had genital warts.

6.  100 types of HPV ( double stranded DNA virus)  Viral replication takes place only in fully differentiated epithelium.  Cutaneous and mucosal types, High, intermediate and low risk types  Papule or plaque  can also remain dormant within epithelial cells without visible disease  HPV type 2 on hands and feet

7.  Benign lesion: the viral genome replicates separately to the host cell’s DNA.  Malignant lesion: the HPV DNA is integrated into the host cell’s chromosomes.  After integration a series of events leads to deregulation of the E6 and E7 genes of HPV.

8.  5 - Fluoruracil (5-Fu) Antimetabolic  Bichloroacetic or Trichloroacetic Acid Tissue Chemical Destruction  Cryotherapy Physical Freezing  Surgical Excision or Curettage Surgical Removal  Cautery Tissue Physical Destruction  Imiquimod Immunomodulator  Interferon Antiviral(immunomodulator)  CO2 Laser Tissue Vaporization  Podophyllin Antimitotic  Podophyllotoxin Antimitotic  Vacinne Antiviral(immunomodulator)

9. Claudio S Batista, Álvaro N Atallah, HumbertoSaconato, Edina MK da Silva 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

11.  Types of studies, Only randomized controlled trials (RCTs) were included in this review  Types of participants, Women and men aged 18 years or more, nonimmunocompromised, with clinical or subclinical genital warts.

12.  5-FU Vs placebo  5-FU 5% Vs Meta-cresol-sulfonic Acid (MCSA)  5-FU 5% Vs Podophyllin  5-Fu 5% Vs CO2 Laser  5-FU 5% Vs 5-FU 5% + INF -2a (Low dose)  5-FU 5% Vs 5-Fu 5% + INF -2a (High dose)  5- FU 5% Vs 5-FU 5% + CO2 Laser + INF -2a (High dose)  5-FU 5% + CO2 Laser Vs CO2 Laser plus

13. Primary Outcomes  Patient or warts response: cure or partial improvement  Recurrence rate Secondary Outcomes  Local reactions  Other related adverse events (alteration in lab data)

14.  Botacini et al, 1993,5% vag. gel 5 gr Qod x15  Females with HPV infection  64 Vs 16  The outcomes after 12 wks Rx were:  Cure(-ve colpo, pap & Bx): 52/64 vs 5/16 * 0.02  Partial response (only+ve cyto): 7/64 vs 1/16  No response: 5/64 vs 10/16 *

15.  Syed at al, 2000, 1% vag. gel 4 gr Qod x4 wks  30 females in each group with intravaginal warts  312 genital warts: 162 Vs 150  The results were:  Cure (Nl colpo & -ve HPV): 25/30 Vs 4/30 * 0.02  side effects : 2/30 Vs 1/30  Lesion recurrence : 2/30 Vs 1/30  Warts cure:141/162 lesions Vs 21/150 * 0.0001  Low index of side effects ( local Rxn, dysuria & local hypersensitivity )

16.  Weissmann et al, 1982, 0.5% gel. Anogenital warts  59 patients: 30 male (14 Vs 16) & 29 female (16 Vs 13 )  The results were:  Cure: 18/30 patients (10/14 male & 8/16 female) Vs 8/29 patients (4/16 male & 4/13 female) * 0.031  Improvement: 6/30 patients (2/14 male & 4/16 female) Vs 4/29 patients, (1/16 male & 3/13 female),  No response: 6/30 patients (4/14 male & 2/16 female) Vs 17/29 patients (8/16 male & 9/13 female). * 0.0068

17.  Data from these 3 studies Botacini 1993; Syed 2000; Weismann 1982 could be pooled but demonstrated heterogeneity (I 2 = 62%).  [RR 0.39 (95% CI, 0.23 -0.67)]. NNT = 2

18.  Botacini et al, 1993, all females  74 patients Vs 9 (MCSA Qod x30 days)  Results after 12 weeks were:  Cure: 52/74 Vs 3/9 *  Partial response: 7/74 patients Vs 1/9  No response: 15/74 patients Vs 5/9 * 0.0075

19.  Botacini et al, 1993, all females  74 pts 5-FU 5% gel (2/wk x8 wks),  40 pts Podophyllin 2% (vag.gel 5gr Qod x15)  5 pts Podophyllin 4%. (vag. gel 5gr Qodx15)  The results after 12 weeks:  Cure: 52 patients /19/ 3 *  Partial response: 7 patients/5/1  No response: 15 patients/16/1 * 0.039

20.  Wallin et al, 1977, All males  42 male patients:20 patients(cream qhs x2w) Vs 22 ( solution by doctor weekly x 4)  Withdrawals: 2 Vs 3  The results after 4 and 9 weeks.  Cure after 4 weeks : 10/18 patients Vs 11/19 0.89  Cure after 9 weeks: 6/18 patients Vs 10/19  Recurrence of lesions p less than 0.00001

21.  Data from two studies (Botacini 1993; Wallin 1977) could be pooled and did not demonstrate heterogeneity (I 2 = 32%). [RR 1.26 (95% CI, 0.86 - 1.82)]. NNT = 6

22.  Relakis, 1996, performed 3 study groups all males  Condyloma Acuminatum (CA): cream qhsx5, if no response other 3 courses,  Condyloma Plain (CP): single dose  Condyloma acuminatum & plain (CA+CP): single dose  The only studied outcome was Treatment Failure.  Lesion Recurrence observed in the first year after treatment was considered as Treatment Failure  Side Effects were observed in 11% of the patients treated with 5-FU

23.  In CA group, 33 males Vs 12  Treatment Failure was: 8/33 Vs 4/12 0.53  In CP Group, 156 males Vs 39  Results were: 29/156 Vs 12/39 0.085  In CA + CP Group, 29 males Vs 20  Results were: 14/29 Vs 14/20 0.12

24.  Relakis et al, 1996, all male patients  5FU 2 courses x 5 days + INF 1.5 SC x 6 days  In CA group: 33 Vs 27  Results were 8/33 Vs 7/27 0.88  In CP group: 156 Vs 18  Results: 29/156 Vs 2/18 0.34  In CA + CP Group: 29 patients Vs 0  Results 14 patients

25.  Relakis et al, 1996, all males  5FU 5% cream 2 courses x 5days + INF 3 IU SC x 6 days  In CA Group: 33 Vs 0  Treatment Failure in 8/33  In CP Group: 156 patients Vs 58  Result: 29/156 Vs 1/58  In Ca + CP Group : 29 Vs 0  Result: 14/29 patients

26.  Relakis et al., 1996, All males  CO2 laser after 2 courses of 5FU cream  In CA group: 33 Vs 30.  Results: 8/33 patients Vs 0/30 0.056  In CP group: 156 Vs 20  Results: 29/156 Vs 1/20 0.18  In CA + CP group: 29 Vs 16  Results: 14/29 patients Vs 3/16  Treatment failure * 0.00001

27.  Carpinello et al., 1988, all males  5FU 5% one wk after Laser x 30 days  68 patients, 41 Vs 27  The outcome studied was Lesion Recurrence  Even one lesion after treatment  Results: 28/41 Vs 19/27 0.86

28.  Considering cure alone, 5-FU was superior to placebo, to MCSA and the Podophylin  considering only treatment failure/ no response, 5-FU was superior to placebo, to MCSA, Podophylin 2% and equal to CO2 Laser and 5FU + INF-2a (low dose) and inferior to 5-FU + INF - 2a ( high dose) and 5FU + Co2 Laser +INF- 2a (high dose).

29.  There was no statistical significance between the treatments of 5-FU + INF - 2a (high dose) and 5-FU + Laser of Co2 + INF- 2a (high dose).  5-FU is a good treatment option in view of the costs of INF- 2a and the CO2 Laser.

30.  Six trials involving 988 pts (645 women and 343 men) and reporting 8 comparisons were evaluated.  Two studies reported withdrawals and dropouts.  5-FU presented better results for cure than placebo or no treatment (relative risk RR 0.39), meta-cresol-sulfonic acid (MCSA) (RR 2.11, 95% ), Podophyllin 2%, 4% or 25% (RR 1.26, 95% CI 0.86 to 1.82).

31.  There were no statistical differences for treatment failure for 5-FU Vs CO2 Laser (RR 0.69, 95% CI 0.43 to 1.11) Vs 5-FU + INF-2a (low dose) (RR 1.02, 95% CI 0.87 to 1.119).  Worse results were found for 5-FU Vs 5-FU + INF-2a (high dose) (RR 10.78, 95% CI 1.50 to 77.36), and 5-FU + CO2 Laser + INF-2a (high dose) (RR 7.97, 95% CI 2.87 to 22.13).

32. Thank You