The rate of new infections declines with age, and new infections typically do not progress to CIN 2 or worse disease in older women; thus, overall potential benefit of prophylactic vaccination or frequent HPV screening to prevent or detect new carcinogenic HPV infections at older ages is low.

We confirm the early decline of HPV infection with age but note increased prevalence after menopause, which could be related to a second peak of HSILs, an observation that warrants further investigation. At least 80% of HPVs involved in cervical carcinogenesis in this population have been characterized. Polyvalent vaccines including the main cancer-associated HPV types may be able to prevent most cases of cervical disease in this region.

No abstract

This paper reports on the enrollment phase of a population-based natural history study of cervical neoplasia in Guanacaste, a rural province of Costa Rica with consistently high rates of invasive cervical cancer. The main goals of the study are to investigate the role of human papillomavirus (HPV) infection and its co-factors in the etiology of high-grade cervical neoplasia, and to evaluate new cervical cancer screening technologies. To begin, a random sample of censal segments was selected and enumeration of all resident women 18 years of age and over was conducted with the aid of outreach workers of the Costa Rican Ministry of Health. Of the 10 738 women who were eligible to participate, 10 049 (93.6%) were interviewed after giving written informed consent. After the interview on cervical cancer risk factors was administered, a pelvic examination was performed on those women who reported previous sexual activity. The pelvic examination included a vaginal pH determination and collection of cervical cells for cytologic diagnosis using three different techniques. Additional cervical cells were collected for determination of the presence and amount of DNA from 16 different types of HPV, and two photographic images of the cervix were taken and interpreted offsite by an expert colposcopist. Finally, blood samples were collected for immunologic and micronutrient assays. Women with any abnormal cytologic diagnosis or a positive Cervigram, as well as a sample of the whole group, were referred for colposcopy, and biopsies were taken when lesions were observed. The enrollment screening will serve as the basis for a prevalent case-control study, and the members of the cohort free from serious disease will be followed actively, at intervals of no more than a year, to study the natural history of HPV infection and the origins of high-grade squamous intraepithelial lesions (HSIL). Details of the field operation are outlined, with particular reference to the realization of this kind of study in developing countries. Descriptive data on the prevalence of disease and exposure to various risk factors are also presented.

Cervicovaginal human papillomavirus (HPV) viral load has been purported as a potential marker for the detection of high-grade cervical intraepithelial neoplasia or cancer (CIN2). To examine disease association with type-specific viral load for the full-range of anogenital HPV infections, we conducted cross-sectional and prospective analyses of 2,000 HPV-infected women from a 10,000-woman population-based study in Guanacaste, Costa Rica with 7 years of follow-up. Cervical specimens were tested for >40 HPV types using a MY09/MY11 L1 consensus primer PCR method with type-specific dot blot hybridization and PCR signal intensity as a measure of viral load. A positive association was observed between prevalent CIN2 and high viral load compared to low viral load for women with baseline single HPV16 infections (OR 5 19.2, 95% CI 5 4.4-83.2) and single non-16 carcinogenic infections (OR 5 9.2, 95% CI 5 2.1-39.9). Inclusion of women with multiple HPV types did not substantially change these associations. In prospective follow-up, only women infected with HPV16 alone (OR 5 27.2, 95% 5 3.5-213.5) had a strong association between high viral load and incident CIN2; non-16 carcinogenic high viral load was not associated with incident CIN2 (OR 5 0.7, 95% CI 5 0.2-1.9). Single noncarcinogenic type viral load was not associated with increased risk of prevalent or incident CIN2 (OR 5 1.2 and 1.1, respectively). In conclusion, carcinogenic high viral load was associated with prevalent CIN2; however HPV16 was uniquely associated with incident CIN2. The extent to which these observations can be translated into clinical practice must be rigorously examined in the context of the method of viral load measurement and the type-specific differences observed for incident CIN2. ' 2007 Wiley-Liss, Inc.Key words: human papillomavirus; viral load; genotype; screening Human papillomaviruses (HPV) are the causal agent of invasive cervical cancer.1 Current screening guideline in the US incorporate HPV DNA testing of cervical samples to clarify equivocal Pap tests and as an adjunct to cytology in primary screening among women over age 30 years. A negative HPV test greatly reduces the risk of a cancer precursor. This allows women with equivocal cytology to return to the general screening pool and women 30-years and older with normal cytology and no high-risk HPV to extend their screening interval to 3 years. Although HPV testing is clinically useful, many women with self-limited carcinogenic HPV infections test positive and are subjected to unnecessary procedures. Therefore, identifying markers that indicate which HPV infections will persist and result in progression to cancer precursors is an important research objective.High concentration of HPV DNA in cervical specimens (HPV viral load) [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] has been evaluated as a marker for the presence of prevalent cervical cancer precursors (defined in the United States for treatment purposes as CIN2 or worse, CIN2) or incident CIN2. Following a typical infectio...