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Key words: cervical intraepithelial neoplasia; human papillomavirus; condom use; clinical coursePersistent infection of the cervical epithelium with high-risk types of HPV plays a major role in the development, maintenance and progression of CIN. 1,2 HPV has been found in 99.7% of cervical cancers worldwide. 3 Sexual intercourse is the primary mode for transmission or acquisition of HPV, and prevalence is related to many determinants involving sexual behavior characteristics. 4 -6 Case-control studies of male sexual partners of women with cervical cancer have shown a relation between male sexual behavior and cervical cancer. 7,8 The presence of HPV DNA in penile swabs conveyed a 5-fold risk of cervical cancer to their wives. 5 Studies on the risk factors of CIN supported a protective effect of condom use in women, emphasizing the venereal nature. 9 -11 Coker et al. 12 found that among high-risk HPV-positive women longer-duration barrier method use was associated with a reduced risk of CIN. Manhart and Koutsky 13 reported in a meta-analysis that data on effects of condom use preventing HPV infection and HPV-related conditions were inconsistent. However, none of these studies was conducted explicitly to assess the effectiveness of condoms at preventing HPV infection and HPV-related conditions.Previously, we showed that flat penile lesions are associated with the presence of HPV and that regression is dependent on the presence of HPV 14 (see also Bleeker and Hogewoning, 2003, accompanying paper). Continuous transmission of HPV in sexual partners having HPV-associated genital lesions might reduce the chance of viral clearance. In a randomized clinical trial, we investigated the influence of condom use on the clinical course of HPV-associated genital lesions and HPV infection in sexual partners. In the present report, we evaluate the effects of condom use on CIN regression and HPV clearance. MATERIAL AND METHODS Study population and designWomen referred to the colposcopy clinic of the Albert Schweitzer Hospital, Dordrecht, the Netherlands, from January 1995 to June 2002 were asked to bring in their male sexual partner. Eligible were women with an abnormal cervical smear (mild dysplasia or worse) and/or cCIN and/or hCIN. Women were evaluated for CIN by colposcopy and by histologic evaluation of cervical biopsy specimens at baseline. Cervical smears were taken for cytology and HPV testing by PCR. The outline of the study was verbally explained and written information given to couples who had no other sexual partners. Willing couples returned within 2 weeks to discuss the study protocol in detail, and additional questions were answered. Both the period of condom use, i.e., only during the study and for at least 3 months, and the instructions on condom use, i.e., during genital-genital contact, were discussed with participants. Latex condoms (Durex fetherlite; Netherlands LRC, Leerdam, the Netherlands) with basic lubricant (without spermicidal and/or virus-inactivating substances) were given free, to increase study com...

In sexually active couples, HPV type concordance was more prevalent than expected by chance and was associated with increased viral loads. These data provide biological support for HPV transmission between sex partners.

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An increased high-risk human papillomavirus (hrHPV) viral load in cervical scrapings has been proposed as a determinant for highgrade cervical intraepithelial neoplasia (CIN) and cervical cancer ( CIN 2), but data so far for HPV types different from HPV 16 are limited and inconsistent. In addition, a viral load threshold to distinguish hrHPV positive women without CIN 2 still has not been defined. Here, we used baseline cervical scrapings of women with normal cytology participating in a large population-based cervical screening trial (i.e. POBASCAM) who were GP51/61-PCR positive for 4 common hrHPV types, i.e. HPV 16, 18, 31 or 33, as a reference to arbitrarily define various viral load thresholds (i.e. 25th, 33rd, 50th, 67th and 75th percentiles of the lowest viral load values) for distinguishing women having single infections with these types without high-grade CIN. Viral load assessment was performed by real time type-specific PCR. The viral load threshold values were subsequently validated on abnormal cervical scrapes of 162 women with underlying, histologically confirmed CIN lesions containing 1 of these 4 hrHPV types. All 59 women with CIN 3 had viral load levels that were higher than those of 33% of the women with normal cytology containing the respective hrHPV type detectable by GP51/61-PCR (i.e. higher than the 33rd percentile of viral load). By using this 33rd percentile viral load cut-off, sensitivity for CIN 3 of 100% (95% CI 93.9-100) was obtained. Hence, application of this viral load threshold would increase the specificity of HPV testing for HPV 16, 18, 31 and 33-associated prevalent CIN 3 without the cost of a marked reduction in sensitivity. In practice, on the basis of viral load analysis, a less aggressive management can be foreseen for 33% of the women with normal cytology participating in a population-based screening program who are GP51/61-PCR positive for HPV 16, 18, 31 or 33. ' 2006 Wiley-Liss, Inc. Key words: HPV; viral load; CIN; real time PCRThe relationship between high-risk human papillomavirus (hrHPV) infection and cervical cancer has become evident from epidemiological and functional studies. 1-3 hrHPV DNA has been detected in almost all cervical squamous cell carcinomas and adenocarcinomas. This finding has led to the widely accepted concept that hrHPV infection is a necessary cause of cervical cancer. [1][2][3] The close association between hrHPV and cervical cancer has resulted in the use of hrHPV testing on cervical scrapes for the detection of cervical cancer and its precursor stages. Several studies have shown that addition of hrHPV testing to cervical cytology improves the sensitivity and negative predictive value for highgrade cervical intraepithelial neoplasia (CIN) and cervical cancer ( CIN 2) compared with cytology alone. 4,5 However, the positive predictive value of the hrHPV test is relatively low because many hrHPV positive women will clear the virus. Especially, hrHPV positive women with cytomorphologically normal smears fall in this category. As a consequence, seve...