Performance of cytology and human papillomavirus testing in relation to the menstrual cycle

Abstract

Cervical smears prepared around the time of menses have been linked to unsatisfactory specimens and false negative results; however, it is unclear whether liquid-based cytology is similarly affected and data relating date of last menstrual period (LMP) to human papillomavirus (HPV) DNA testing are conflicting. Accordingly, we evaluated liquid-based cytology and HPV test results using Hybrid Capture 2 and PCR by LMP (days 0 -10; 11 -21; 22 -28). We studied 5060 participants in ALTS, the Atypical Squamous Cells of Undetermined Significance (ASCUS) Low Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. On average, women had 3.4 examinations (median 4, range 1 -5) during a 2-year period of observation permitting an examination of intra-individual variation in cytology and HPV by LMP. Although uncommon, unsatisfactory cytology specimens were most likely on days 0 -10. For satisfactory specimens, the frequency with which cytologic categories were reported varied by time since LMP, although differences were modest and did not affect the chance of abnormal cytology or its severity among women diagnosed with CIN2 þ . The frequency of positive HC2 tests did not vary with date of LMP. Among HPV infected women, independent of eventual diagnosis and the number of viral genotypes present, mid-cycle specimens yielded the highest frequency of LSIL cytologic interpretations and the highest HPV load; however, the magnitude of these effects were small. Intraindividual correlations of cytology or HPV by LMP were generally weak. We conclude that mid-cycle specimens yield slightly higher HPV DNA loads and slightly increased LSIL interpretations, but the clinical impact is marginal. Standardizing collection times would slightly improve interpretation of trends in HPV load. Finally, these data are consistent with the view that the biological properties of the HPV-infected cervix vary with the date of the LMP. Historically, clinicians have recognized that cytologic samples collected on days of active menstruation are typically bloody and often yield smears that are hypocellular, obscured, and lack endocervical cells (Vooijs et al, 1987). Furthermore, data demonstrating that unsatisfactory cytology specimens are associated with a higher than expected frequency of cervical intraepithelial neoplasia (CIN) and carcinoma (Ransdell et al, 1997;Nygard et al, 2004) in later follow-up, suggest that that these specimens may be linked to false negative results. However, efforts to coordinate return visits to re-screen women with unsatisfactory cytology often fail (McGarahan and Smith-McCune, 2005), and presumably, deferring screening for women who present near the time of menses would present similar problems. Given this dilemma, it is important to determine whether the advantages of liquid-based cytology methods, such as increased cellular recovery and reduction of obscuring by blood (Bernstein et al, 2001), eliminate the association between the performance of cytology and LMP that has been demonstrated for smears.Similarly, the implement...

Effect of the Menstrual Cycle and Hormonal Contraceptives on Human Papillomavirus Detection in Young, Unscreened Women

“…Another large study investigating high-risk HPV detection within the menstrual cycle showed a small midcycle increase of HPV detection. 9 However, data on OCP use are not reported and therefore it is difficult to compare this study with our results. A smaller study by our group, in nonusers, found a higher rate of HPV-positive samples in the follicular phase.…”

Cervical human papillomavirus detection is not affected by menstrual phase

“…Only one other study evaluated HPV viral load, and investigators found a modest increase during midcycle. 4 It is unclear why viral load detection would be higher for specimens collected during this time, but it has been suggested that peak oestrogen levels at midcycle could promote this effect by enhancing HPV viral replication, or by reducing cellular adhesion. 4 In this study, we found no indication that viral load varies with menstrual phase.…”

“…It is not clear whether the phase of a woman's menstrual period at the time of cervical sampling has an effect on HPV detection, as previous studies have provided conflicting results. [1][2][3][4][5][6] A recent study exploring the effect of oral contraceptive (OC) use on HPV detection revealed a higher detection rate during the follicular phase among non-users, whereas OC users experienced a higher detection rate during the luteal phase. 7 Using data collected in the Ludwig-McGill cohort study conducted in Brazil, we evaluated the effect of menstrual phase on HPV detection, and attempted to validate previous findings concerning OC use.…”

Human papillomavirus (HPV) genotypes and HPV16 variants in human immunodeficiency virus-positive Italian women

“…The present analysis included 112 HIVpositive and 115 HIV-negative women who had at least three visits during the 3-year follow-up. The aims of the study were: (i) to identify viral infections variably detected in a single cervical swab (Sherman et al, 2006) and (ii) to assess the relationship between HPV genotypes and cytological results. During each visit, cervical cell scrapings were collected with a cytobrush from the ecto-and endocervix of each woman and after spreading of cells on slides (Pap smears), the remaining cells were suspended in 1 ml lysis buffer [10 mM Tris/HCl (pH 7.6), 5 mM EDTA, 150 mM NaCl, 1 % SDS] and stored at 220 uC until analysis.…”