Researchers note high efficacy of trial vaccine against HPV

January 2005

A new vaccine in trials has shown promising results against human papillomavirus (HPV), according to researchers. The vaccine is intended to immunize women against HPV-16 and HPV-18.

Diane Harper, MD, and colleagues from Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., conducted a blinded, randomized trial involving 1,113 women from the United States, Canada and Brazil. The participants received either three doses of the experimental virus-like particle vaccine (GlaxoSmithKline Biologicals) or placebo over the course of three months.

Study participants

The women involved were between the ages of 15 and 25 years and had no more than six sexual partners. They also had no history of abnormal Pap smears or ablative or excisional treatment of the cervix and were not receiving treatment for condylomata. The women were all cytologically negative, seronegative for HPV-16 and HPV-18 antibodies by enzyme-linked immunosorbent assay and HPV DNA–negative by polymerase chain reaction for 14 high-risk HPV types no more than 90 days prior to the study.

Methods

The researchers examined vaccine efficacy in preventing persistent HPV-16/18 infection and incident infection, including the vaccine’s efficacy in the prevention of cytologically confirmed low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL), and histologically confirmed LSIL (cervical intraepithelial neoplasia [CIN] 1), HSIL (CIN 2 or 3), squamous cell cancer and adenocarcinoma associated with HPV-16/18 infection.

Each woman participating in the study received a 0.5-mL dose of either vaccine or placebo at zero, one and six months. Cervical specimens were taken at six, 12 and 18 months. Women obtained their own cervico-vaginal samples with two sequential swabs at zero and six months, and then every three months.

During the first seven days after vaccination, women recorded any symptoms on diary cards using a three-grade scale of symptom intensity. Within the first 30 days after vaccination, all of the women reported to study personnel for an interview about all adverse events.

The researchers discovered similar risk factors for HPV between the groups. The average age of the women enrolled was 20 years. Many had between two and five sexual partners; most began sexual activity between 15 and 19 years of age. About half of the women were smokers.

Efficacy against incident HPV infections

Of the 366 women in the vaccine group who were involved in the study according to protocol, which meant receiving all three vaccines and responding to follow-up appointments, a cervical sample detected no incident cases of HPV-16 and two incident cases of HPV-18 (0.6%) at the 18-month follow-up. Of the 355 women who received the placebo, 18 cases of HPV-16 were detected at the 18-month follow-up (5.1%), and seven cases of HPV-18 (2.0%) were detected (P < .0001).

Using a combined cervicovaginal and cervical sample at the 27-month follow-up, the researchers detected six cases of HPV-16 in the vaccine group (0.9%) and 29 cases (4.6%) in the placebo group (P < .0001). Six cases of HPV-18 were also detected in the vaccine group (0.9%) and 16 cases (2.5%) in the placebo group (P = .021).

Among the 560 women involved in the vaccine group who did not follow protocol, the researchers detected five cases (0.7%) of HPV-16 using a cervical sample at the 27-month follow-up. The placebo group contained 553 women; 30 cases (4.6%) were noted (P < .0001). They detected three cases of HPV-18 in the vaccine group (0.4%) and 17 (2.6%) in the placebo group (P = .002).

Fourteen cases of HPV-16 (1.7%) were detected in the vaccine group during the 27-month follow-up using combined cervicovaginal and cervical samples. The researchers noted 53 cases of HPV-16 (6.9%) in the placebo group (P <.0001). Thirteen cases of HPV-18 (1.6%) were noted in the vaccine group, and 31 cases (3.9%) were noted in the placebo group (P = .0001).

Persistent HPV infections

The researchers found the vaccine showed 100% efficacy against persistent HPV-16 and HPV-18 in the 366 women in the vaccine group who followed protocol at the 18-month follow-up.

Efficacy was rather high even among the vaccine recipients who did not follow protocol. Using cervical samples at month 27 of follow-up, researchers detected one case of HPV-16 (0.1%) in the vaccine group and 16 cases (2.5%) in the placebo group (P = .0002). No cases of HPV-18 were noted in the vaccine group, and five cases (0.8%) were noted in the placebo group (P = .025).

Using combined cervicovaginal and cervical samples, four cases of HPV-16 (0.5%) were noted in the vaccine group at the 27-month follow-up. Twenty-five cases (3.2%) were detected in the placebo group (P < .0001). One case of HPV-18 (0.1%) was noted in the vaccine group, and 11 cases (1.4%) were noted in the placebo group (P = .003).

Vaccine efficacy was 92.9% against cytologic abnormalities associated with HPV-16/18 infection, in the intent-to-treat analysis. The vaccines were shown to be 100% effective against lesion development (CIN 1, CIN 2).

What’s next?

No serious adverse effects were noted. The vaccine group did experience more pain, swelling and redness at the injection site, but the symptoms were mild and had no effect on the completion of the study. Fatigue, gastrointestinal complaints, headache, itching and rash were similar in both groups.

With 100% vaccine efficacy regarding persistent HPV-16/18 infections, this preliminary study yields promising results and urges more research into the HPV vaccine. According to the researchers, large-scale trials with long-term follow-up are needed. The findings of this study suggest that the vaccine could contribute to substantially reducing cervical cancer, which is one of the leading causes of cancer mortality in women worldwide and has been shown in other studies to be a serious result of infection with certain types of HPV.

For more information:

• Harper DM, Franco EL, Wheeler C, et al. Efficacy of bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomized controlled trial. Lancet. 2004;364(9447):1757-1765.
• GlaxoSmithKline Biologicals funded and coordinated the study.
• Dr. Harper has no direct financial interest in GlaxoSmithKline.