Elsevier

Journal of Infection

Volume 72, Issue 1, January 2016, Pages 60-69
Journal of Infection

Cervical HPV natural history among young Western Cape, South African women: The randomized control EVRI Trial

https://doi.org/10.1016/j.jinf.2015.10.001Get rights and content

Summary

Objective

The objective of this analysis was to assess human papillomavirus (HPV) infection persistence and incidence 7-months post-enrollment by HPV vaccine study arm (vaccine or placebo).

Methods

HIV-negative, sexually active women aged 16–24 years in the Western Cape, South Africa, were enrolled in the EVRI Trial and were randomized to receive 4-valent HPV vaccine or placebo. Cervical specimens were collected at enrollment and at the 7-month visit and were genotyped for HPV. HPV prevalence, persistence, and incidence were calculated. Prevalence ratios and odds ratios were calculated to assess factors associated with a prevalent and incident HPV infection.

Results

HPV incidence rates were marginally higher for the placebo group (n = 163) compared to the vaccine group (n = 169). A large proportion of the prevalent high-risk (HR-HPV) HPV types (49%) persisted over the 7-month period in both arms. Prevalent HR-HPV infection was significantly associated with a prevalent gonorrhea infection and detection of Herpes simplex type 2 antibodies. Incident HR-HPV infection was significantly associated with abnormal cervical cytology at enrollment and younger age.

Conclusions

Women living in geographic areas, such as southern Africa, at high-risk for HPV need to receive HPV vaccination at a very young age to maximally prevent infection and subsequent disease.

Introduction

Human papillomavirus (HPV) is the most common sexually transmitted infection (STI), one that can infect multiple anatomic sites in both men and women. Persistent HPV infection is the necessary cause of cervical cancer and causes 90% of anal, 50% of penile, 43% of vulvar, 70% of vaginal, and 33–72% oropharyngeal cancers worldwide.1, 2 Women and men residing in southern African countries have among the highest burden of HPV infection and related cancers worldwide.3, 4, 5, 6

There are two licensed HPV vaccines that are highly efficacious in preventing 70% of cervical disease among women through protection against HPV16 and HPV18 infections. Recently a 9-valent HPV vaccine was licensed in the United States that increases prevention of cervical disease to 90% through the protection from HPV types 16, 18, 31, 33, 45, 52, and 58.7 The uptake of the vaccine is of major public health importance, especially in countries that have no or poor cervical cancer screening programs.

Within the context of a Phase II Trial to assess the feasibility of conducting a placebo-controlled randomized HPV vaccine trial to prevent HIV infection, we assessed cervical HPV status at enrollment and 7-months post-enrollment among women at high-risk for HIV.

Section snippets

Population

Women residing in the Western Cape, South Africa were enrolled from November 2012 to July 2013 in a preparedness study, the Efficacy of HPV Vaccine to Reduce HIV Infection (EVRI) Trial (NCT01489527). A full description of study procedures and conduct of the trial has been published elsewhere.8 Briefly, women aged 16–24 that were HIV-negative and non-pregnant were enrolled in a Phase II randomized controlled trial of Gardasil (4-valent HPV (4vHPV) vaccine) vs. placebo (saline).

Trial-eligible

Results

The vaccine treatment groups were similar with respect to their enrollment demographic characteristics (Table 1). However, women randomized to receive the HPV vaccine were more likely to have ever been pregnant, have more male lifetime sexual partners, and have abnormal cervical cytology compared to women randomized to receive the placebo. Although women reported a wide range of number of lifetime sexual partners, the median number of partners reported was only two among those receiving placebo

Discussion

We have described the incidence, prevalence and persistence of cervical HPV among young South African women participating in randomized placebo-controlled HPV vaccine trial. The study arms were comparable in their enrollment demographic characteristics and prevalence of vaccine HPV types (6/11/16/18). Prevalence and incidence of cervical HPV was very high in this study population of women residing in a community of high HIV prevalence. The data presented here clearly demonstrate rapid cervical

Conflicts of interest

A.R.G. is on the Speaker's Bureau of Merck. M.F.S.v.d.L. received research funding from Sanofi-Pasteur MSD; he is a co-investigator in a Sanofi-Pasteur MSD HPV vaccine trial; he sat on a vaccine advisory board of GSK. For the remaining authors, no conflicts of interest were declared.

Funding source

Merck (IISP39582) was the main sponsor of this trial and provided the study product. This work was also supported by the National Cancer Institute at the National Institutes of Health (Cancer Prevention Fellowship R25T CA147832 to S.L.S.).

Acknowledgments

The authors acknowledge the contributions of Charlotte Lawn, Wendy Adendorff, Zukiswa Gloria Ncume, Kayoko Kennedy, Dale Barrios, Jeannie Vaughn, David Jackson, Shahieda Isaacs, Nafiisah Chotun, Donna J. Ingles, and all study participants, without whom this study would not have been possible.

References (30)

  • M.J. Levin et al.

    Safety and immunogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine in HIV-infected children 7 to 12 years old

    J Acquir Immune Defic Syndr (1999)

    (2010 Oct)
  • R. Herrero

    Human papillomavirus (HPV) vaccines: limited cross-protection against additional HPV types

    J Infect Dis

    (2009 Apr 1)
  • J.S. Smith et al.

    Age-specific prevalence of infection with human papillomavirus in females: a global review

    J Adolesc Health Off Publ Soc Adolesc Med

    (2008 Oct)
  • A.C. McDonald et al.

    Distribution of human papillomavirus genotypes among HIV-positive and HIV-negative women in Cape Town, South Africa

    Front Oncol

    (2014)
  • E.L. Franco et al.

    Epidemiology of acquisition and clearance of cervical human papillomavirus infection in women from a high-risk area for cervical cancer

    J Infect Dis

    (1999 Nov)
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