Visit our new HPV Vaccine Section: NCCC SECTION ON THE HPV VACCINE

This area provides important information regarding Human Papillomavirus (HPV), including some of the latest cancer trials and information on upcoming vaccines. Please choose an area of interest from the menu on the right.

HUMAN PAPILLOMA VIRUS (HPV):

A virus that is the cause of warts of the hands and feet, as well as lesions of the mucous membranes of the oral, anal and genital cavities. More than 50 types of HPV have been identified, some of which are associated with cancerous and precancerous conditions. The virus can be transmitted through sexual contact and is a precursor to cancer of the cervix. There is no specific cure for an HPV infection, but the virus often can be controlled by podophyllin (medicine derived from the roots of the plant Podophyllum peltatum) or interferon, and the warts can be removed by cryosurgery, laser treatment or conventional surgery. Some scientitsts believe HPV can "clear" out of the body.

 

CDC Report to Congress, Prevention of HPV and cervical cancer, July 2004

 

Dear Colleagues:

 

Genital HPV infections are estimated to be the most common sexually transmitted infection in the United States (U.S.), with roughly 5.5 million persons becoming newly infected each year. Although the majority of infections cause no symptoms, are self-limited, and go away on their own without clinical consequences, genital HPV is of public health concern because persistent infection with certain high-risk types can cause cervical cancer in women. Fortunately, cervical cancer is an uncommon consequence of HPV, especially if women are screened for cancer regularly with Papanicolaou (Pap) tests and followed up with appropriate treatment, and in the past 40 years, widespread cervical cancer screening using the Pap test and treatment of precancerous cervical abnormalities have resulted in a dramatic decrease in cervical cancer incidence and mortality in the U.S. However, in spite of the success of prevention programs, cervical cancer remains an important health issue for women in the U.S., with an estimated 12,200 new cases and 4,100 deaths from cervical cancer occurring each year.

 

To describe the current state of the science on the prevention of genital HPV infections and its associated diseases of genital warts and cervical cancer, the Centers for Disease Control and Prevention (CDC) recently prepared a Report to Congress. The report, entitled the Prevention of Genital Human Papillomavirus (HPV) Infection, describes key aspects of the epidemiology of genital HPV infection and its transmission and reviews strategies for the prevention of genital HPV and its associated diseases. Based on this critical review, the report recommends individual and public health strategies to prevent genital HPV infection and the important complication of cervical cancer.
The National Center for HIV, STD, and TB Prevention (NCHSTP) is pleased to share the enclosed report with you and your constituents. Key recommendations from the report are as follows:

 

Priorities for Public Health Agencies
  • Promote increased cervical cancer screening of never- and rarely screened women and appropriate follow-up for those with abnormal Pap tests.
  • Work with public and private partners to increase awareness among health care providers and the general public about prevention of genital HPV infection and cervical cancer.
  • Collaborate with private industry to promote and accelerate the development of a safe and effective HPV vaccine.
  • Continue epidemiologic, laboratory, and behavioral research on genital HPV infection, including studies of the prevalence of HPV in the United States,
  • Research on the attitudes and concerns of women diagnosed with HPV infection (e.g., concerns about cancer or about transmission), and surveys of provider knowledge and practices regarding HPV.
Individual Strategies for Preventing Genital HPV Infection and Cervical Cancer
  • Regular cervical cancer screening for all sexually active women and treatment of precancerous lesions remain the key strategy to prevent cervical cancer.
  • The surest way to eliminate the risk for future genital HPV infections is to refrain from any genital contact with another individual. For those who choose to be sexually active, a long-term, mutually monogamous relationship with an uninfected partner is the strategy most likely to prevent genital HPV infections. However, it is difficult to determine whether a partner who has been sexually active is currently infected. For those choosing to be sexually active and who are not in long-term mutually monogamous relationships, reducing the number of sex partners and choosing a partner less likely to be infected may reduce the risk of genital HPV infection. Partners less likely to be infected include those who have had no or few sex partners.
  • While available scientific evidence suggests that the effect of condoms in preventing HPV infection is unknown, condom use has been associated with lower rates of the HPV-associated diseases of genital warts and cervical cancer. The available scientific evidence is not sufficient to recommend condoms as a primary prevention strategy for the prevention of genital HPV infection. There is evidence that indicates that the use of condoms may reduce the risk of cervical cancer.
  • In the future, receiving a safe and effective HPV vaccine to help prevent genital HPV infection, as well as the HPV-associated diseases of genital warts and cervical cancer, would be an important prevention measure. However, an effective HPV vaccine would not replace other prevention strategies.
To view entire report in Adobe Acrobat click here.

CERVICAL CANCER AND OTHER HPV-RELATED STUDIES

Portland Kaiser Cohort Study of HPV and Cervical Neoplasia

 

The Portland Kaiser Permanente cohort study of human papillomavirus (HPV) infection and cervical neoplasia was established in 1989-1990 by enrolling almost 24,000 women obtaining routine Pap smear screening at any one of seven Portland Kaiser-Permanente screening clinics. The enrollment phase yielded a prevalent case-control comparison which demonstrated that HPV was the primary risk factor for cervical intraepithelial neoplasia explaining other traditional risk factors, an "atypia" study which showed HPV testing could be used to clarify borderline smears, and a study of determinants of HPV DNA in controls and several ancillary studies on the women with atypia. In the prospective years of the project, we have focused on 3 sub-cohorts: the incidence , recurrence, and progression cohorts. An incident case-control study based on the first five years of follow-up has been published. The full cohort based on up to 10 years of follow-up is underway.

 

The Guanacaste Study of HPV Natural History

 

Guanacaste Province is an area in Costa Rica with a very high incidence rate of cervical cancer. This prospective cohort study of HPV infection and cervical neoplasia is based on the recruitment and ongoing 7-year follow-up of a random sample of approximately 10,000 women 18+ years of age, residing in Guanacaste. The study is the companion to the prospective study of HPV and cervical neoplasia in Portland, which is a very low-risk, well-screened, mainly white middle-class U.S. population. Enrollment in 1993-1994 included a personal interview, cervical cytologic smears, Cervicography, cervical swabs for HPV, and a blood specimen. Participation was about 93% and all women with any screening abnormality were referred for colposcopy and biopsy. The prevalent phase of the study permitted several studies of HPV infection, cytology, Cervicography, and the whole spectrum of cervical neoplasia. The epidemiologic risk factors for each stage of neoplasia were identified, controlling for the central role of type-specific HPV infection. Follow-up of the cohort at six month to yearly intervals depending on disease status is now underway, to examine the origins of high-grade cervical intraepithelial neoplasia.

 

Vaccine Trial

 

A large randomized trial is planned in Costa Rica to evaluate the efficacy of two virus-like particle (VLP)-based prophylactic human papillomavirus (HPV) vaccines developed at NCI. Volunteers in the trial will be screened for cervical disease at entry and will receive three VLP or three placebo vaccinations over the course of six months. Participants will be actively followed for a period of four years and information will be collected on side effects of the vaccine (safety), immune induction by the vaccine (immunogenicity), and the occurrence of cervical disease (efficacy).

 

ASCUS/LSIL Triage Study (ALTS)

 

This project is a study of the clinical management of low-grade cervical cytologic abnormalities. The major hypothesis to be tested is whether HPV testing can reliably triage the common cytologic diagnoses of ASCUS (Atypical squamous cells of undetermined significance) and LSIL (Low-grade squamous intra-epithelial lesions), which represent the bulk of cervical abnormalities seen on Pap smears. Currently, the most aggressive standard of care is immediate colposcopy and biopsy of all suspected lesions. This type of aggressive management is expensive with some associated morbidity, and probably represents over-treatment, since evidence indicates that most cases of ASCUS and LSIL eventually regress. This clinical trial of management alternatives consists of three arms: immediate colposcopic referral of all patients; triage using HPV testing as an adjunct to cytology; and conservative management with repeat Pap smears. All participants are being followed every 6 months for two years. Over 5,000 women were randomized during enrollment that ended in December, 1998.

 

ALTS Immunology

 

The ALTS Immunology Study is a prospective study designed to identify biomarkers associated with a permissive versus protective immune response to low-grade cervical lesions. Approximately 900 women with low-grade cervical disease have been enrolled in this study and are being followed at 6 month intervals for two years. Cellular and humoral immunological responses at entry will be correlated with progression, persistence or regression of low-grade lesions during follow-up. Immunological parameters are also being measured over time in a subgroup of approximately 300 women in our study. Both systemic and local responses are being examined.

 

Cervical Adenocarcinoma Case-Control Study

 

A multi-center case-control study of cervical adenocarcinomas and other rare histological forms of cervical cancer was conducted to examine the role of viral and non-viral exogenous and endogenous factors associated with cervical adenocarcinomas and adenosquamous carcinomas. Incident and histologically confirmed cases of in situ and invasive cervical tumors of glandular histology were ascertained. Two control groups were also selected for study. The first comprised a sample of women with squamous cell cervical cancer and the second comprised population controls selected by a modified random digit dialing method. A total of 595 women agreed to participate in the study. Participants responded to a detailed risk factor questionnaire and had blood and cervical specimens collected for HPV testing and other bioassays of interest.