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Expression patterns of plasma microRNAs in patients with cervical cancer from two teaching hospitals in Ghana.

AIM: Early cervical cancer diagnosis is a global challenge that needs to be addressed by the discovery of less invasive diagnostic and prognostic approaches. Circulating miRNAs are stable in plasma and their diagnostic potentials have been elucidated in some cancers. Therefore, in this cross-sectional study, we determined the patterns of expression of 7 selected circulating microRNAs that differ between patients with cervical cancer receiving therapy, patients with cervical not on therapy and healthy females. The goal was to investigate the diagnostic and prognostic potential of these selected miRNAs. METHODS: Total RNA was extracted from plasma samples collected from 53 participants recruited from Komfo Anokye Teaching Hospital and the Cape Coast Teaching Hospital, Ghana. Complementary DNA (cDNA) synthesis was performed, followed by quantitative polymerase chain reaction (qPCR) to amplify and quantify the expression levels of the target microRNAs. Expression levels of seven microRNAs-hsa-miR-146a, hsa-miR-29a, hsa-miR-29b, hsa-miR-34a, hsa-miR-233, hsa-miR-155, and hsa-miR-27a were compared among three groups: healthy controls (n = 27), patients with cervical cancer on therapy (n = 13), and those not on therapy (n = 13). RESULTS: miR-155 and miR-27a showed statistically significant differential expression between cancer patients and healthy controls. In addition, miR-29b expression levels differed significantly between stage 4b and stage 4a of patient with cervical cancer undergoing treatment. CONCLUSION: These findings suggest that circulating plasma miRNAs may serve as non-invasive biomarkers for the early detection of cervical cancer, monitoring disease progression, and evaluating treatment response.

Humans↗

Bony landmarks are not an adequate substitute for lymphangiography in defining pelvic lymph node location for the treatment of cervical cancer with radiotherapy.

PURPOSE: Curative radiotherapy (RT) for carcinoma of the cervix requires adequate irradiation of regional lymph node groups. The best nonsurgical method of defining lymph node anatomy in the pelvis remains the lymphangiogram (LAG). This study was designed to determine if bony landmarks could accurately substitute for LAG as a means of determining lymph node position for the purpose of pelvic RT treatment planning. METHODS AND MATERIALS: The post-LAG simulation films of 22 patients treated at the Fox Chase Cancer Center for cervical cancer were examined. On anterior/posterior (A/P) simulation films, the distance of lymph nodes was determined from the top, middle, and bottom of the sacroiliac joint, and at the pelvic rim, 1 and 2 cm above the acetabulum. On lateral (LAT) simulation films, lymph node position was measured at points 0, 4, and 8 cm along a line from the bottom of L5 to the anterior aspect of the pubic symphysis. Positive values represent lateral and anterior distances relative to the reference point on A/P and LAT films, respectively. Negative values represent distances in the opposite direction. The adequacy of standard pelvic fields as defined by the Gynecologic Oncology Group (GOG) (A/P: 1.5 cm margin on the pelvic rim; LAT field edge is a vertical line anterior to the pubic symphysis) was also examined. Data are expressed as the mean +/- two standard deviations, (i.e. 95% confidence level). RESULTS: On A/P simulation films, the distance of visualized lymph nodes had mean values of -1.6 +/- 1.7 cm (range -4.1 to -0.4 cm), -1.3 +/- 1.5 cm (range -3.4 to 0.0 cm), and 1.2 +/- 1.8 cm (range -1.0 to 2.6 cm) from the sacro-iliac (SI) joint at the superior, middle, and inferior points, respectively. The mean distance of the nodes from the pelvic rim at points 1 and 2 cm above the acetabulum was 0.3 +/- 1.2 cm (range -0.6 to 1.8 cm) and 0.2 +/- 1.8 cm (range -1.6 to 2.1 cm), respectively. On LAT simulation films, the distance of lymph nodes from points 0, 4, and 8 cm from the previously described reference line had mean values of 2.0 +/- 1.0 cm (range 1.3 to 3.0 cm), 0.9 +/- 3.9 cm (range -1.9 to 5.1 cm), and 1.8 +/- 2.1 cm (range -0.8 to 3.5 cm), respectively. Ten of 22 (45%) patients would have had inadequate nodal irradiation if their fields had been designed according to standard GOG parameters. In all cases, these incompletely irradiated lymph nodes were from the lowest of the lateral external iliac group. CONCLUSION: Great variability in pelvic lymph node location is demonstrated when LAG is used to directly visualize their location. Bony structures are inaccurate landmarks for pelvic lymph node position. The GOG standard pelvic fields are not consistently adequate to cover all lateral external iliac lymph nodes, although the clinical significance of this subgroup of lymph nodes is not known. At this time, LAG remains the ideal radiographic modality to define anatomic location of regional lymph nodes for pelvic RT treatment planning. The clinical importance of the most lateral group of external iliac lymph nodes in various stages of cervical cancer represents a potential area of future research.

Acetabulum↗

Cost-effective analysis of mass screening for cervical cancer in Japan.

Cost-effectiveness analysis for cervical cancer screening in Japan was performed to estimate the cost per life-year saved by the screening; cost-effectiveness ratio (CER). The analysis was made using a simulation model to estimate long-term cost and effectiveness of the screening programs. CER of cervical cancer screening was estimated to be US$ 40,604 which was 2.4 times more expensive than that for gastric cancer screening but was about the same as that for colorectal cancer screening. It was within the range of cost-effectiveness of other cancer screening programs financed under the Health and Medical Services Law for the Aged in Japan. We performed sensitivity analysis on the following seven estimates, the screening charge, the sensitivity and the specificity of the screening test, the frequency of carcinoma in situ (CIS) among cases detected in the screening program, the initial cost and the terminal cost for patients with invasive cancer, and the incidence rate of cervical cancer. The sensitivity analysis demonstrated that the screening charge was the most influential factor on CER. CER was fairly stable under various assumptions on the accuracy of the screening test, the frequency of carcinoma in situ (CIS), the treatment cost for patient, and the incidence of cervical cancer. CER was less sensitive to the changes in incidence, even to as low as a 50% decrease of the current figure. Then if the incidence rate becomes 85% of the current figure in 2015, CER would be US$ 48,176 and it was suggested that the cervical cancer screening would remain reasonably cost-effective until the year 2015.

Adult↗

Hypoxia Response Is Associated with Reduced HPV Activity and Tumor Microenvironment Remodeling in Cervical Cancer.

Human papillomavirus (HPV) significantly influences cervical cancer progression and treatment, yet its interactions with the tumor microenvironment remain incompletely understood. We performed single-cell and spatial transcriptomic sequencing on cervical cancer samples to explore these interactions. By aligning sequencing reads to a merged HPV16-human reference genome, we characterized HPV16 heterogeneity and its association with host states at the single-cell and single-gene levels. E5 transcriptional activity was negatively associated with the host interferon response, indicating a role in immune evasion. A hypoxic environment was correlated with the downregulation of E5 activity and elevated MHC-I expression, which may contribute to stronger interactions between hypoxic cancer cells and cytotoxic CD8⁺ T cells. Additionally, HPV16 integration in host cells was associated with increased fatty acid metabolism. These findings suggest that combining anti-angiogenic drugs and fatty acid metabolism inhibitors has the potential to improve cervical cancer treatment.

Cervical cancer↗

Papillomaviruses and cervical cancer: pathogenesis and vaccine development.

A subset of human papillomaviruses (HPVs) has been implicated as the principal etiologic agents of cervical cancer. Cervical cancers consistently retain and express two of the viral genes, E6 and E7. Although infection with HPV seems to be necessary, other factors, such as cellular immune function, play an important role in determining whether cervical infection will regress, persist, or progress to cancer. The close relationship between viral infection and cancer makes HPV an attractive target for prophylactic and therapeutic vaccines. Candidate vaccines have been shown to have efficacy in animal models, and human clinical trials are planned or in progress.

Animals↗

Expression of keratinocyte growth factor receptor (KGFR/FGFR2 IIIb) in human uterine cervical cancer.

Keratinocyte growth factor receptor (KGFR), also known as FGFR2 IIIb, is a splice variant of FGFR-2. KGFR is expressed in many types of epithelial cell and is activated with four known ligands [FGF-1, FGF-3, FGF-7 (also known as KGF) and FGF-10] that are predominantly synthesized by mesenchymal cells. KGFR is highly expressed in the late-proliferative phase of a normal endometrium and in endometrial adenocarcinoma. In the present study, we attempted to determine the expression and localization of KGFR in human cervical cancer cell lines and cervical cancer tissues. The KGFR protein was detected in CaSki and HeLa cells, but not in ME-180 cells of cervical cancer cell lines. In non-cancer cervical tissues, KGFR immunoreactivity was weakly expressed in the surface of squamous epithelial cells and vascular smooth muscle cells. Immunohistochemically, the KGFR protein was detected in squamous cell carcinoma in 36 of 42 (86%) cervical cancer patients. In cervical cancer tissues, KGFR was detected in 17 of 18 (94%) of patients with the keratinizing type and 19 of 24 (79%) of patients with the non-keratinizing type of cervical cancer. Furthermore, KGFR was prominently localized in proliferating reserve cells and squamous metaplastic reserve cells adjacent to cancer cells. In contrast, KGFR was not detected in cervical ductal cells in cancer or non-cancer cervical tissues. These findings may indicate that KGFR mediates the growth and differentiation of reserve cells and squamous cell carcinoma in the cervix.

Adult↗

Cervical cancer and human papillomavirus: epidemiological evidence and perspectives for prevention.

Cervical cancer is a major public health problem, as it is the second most common cancer in women world-wide after breast cancer. About 80% of the half a million cases estimated to occur annually in the world, occur in developing countries. The epidemiological evidence linking human papillomavirus (HPV) to cervical cancer is reviewed. It is concluded that over 90% of cervical cancers can be attributed to certain HPV types. HPV 16 accounts for the highest proportion (50%) followed by HPV 18 (12%), HPV 45 (8%) and HPV 31 (5%). The association with these HPV types are very strong and consistent with odds ratios over 15 in all case-control studies in high- and low-risk countries for cervical cancer. However, HPV is not a sufficient cause of this malignancy; certain cofactors are necessary for a proportion of HPV persistent infections to eventually progress to cancer. These include host factors such as histocompatibility types and immunological response, hormonal influences and infections with other sexually transmitted agents such as Chlamydia trachomatis. In addition, results from our studies carried out in Spain and Colombia support the hypothesis that male carriers of HPV play an important role in the development of cervical cancer in their wives. The recognition of the central role of HPV in cervical cancer has far-reaching implications for the primary and secondary prevention of this malignancy. Prophylactic and therapeutic HPV vaccines are now under development and HPV typing is being integrated into screening programmes in pilot studies in a few developed countries. In developing countries, well conducted conventional screening programmes remain the best approach for the control of cervical cancer until a safe and efficient HPV vaccine can be used in the general population.

Carcinoma in Situ↗

Breast and cervical cancer surveillance, United States, 1973-1987.

Breast and cervical cancer incidence and mortality rates were reviewed for the period 1973-1987. For breast cancer, mortality has been relatively stable, increasing from 26.9/100,000 women in 1973 to 27.1 in 1987. Alternatively, data from the National Cancer Institute's Surveillance, Epidemiology, End Results Program (SEER) showed a 36% increase in the incidence of this malignancy over the same period. In 1987, overall incidence of invasive breast cancer was 111.9/100,000 women. White women experienced lower overall mortality rates and higher overall incidence than black women; however, these differences varied by age. Examination of breast cancer incidence by stage of disease at diagnosis revealed that rates for distant and regional disease have remained relatively stable since 1973. In contrast, rates of localized and in situ cancers exhibited an increase in the 1980s that may correspond to increased use of mammography in this country. The rate of decline in cervical cancer incidence and mortality has slowed in recent years. In 1987, 3.0 cervical cancer deaths/100,000 women occurred. SEER incidence for invasive disease for that year was 8.2/100,000. Rates varied by race, age, state, and stage of disease. In general, black women experienced much higher incidence and mortality from invasive cervical cancer than white women. For both races, rates of in situ disease were highest among young women and decreased rapidly with age. Rates of in situ cervical cancer were consistently higher than rates of invasive cancer for the time period studied.

Adult↗

A three-gene radioresistance signature predicts tumor progression in cervical cancer.

BACKGROUND: As a primary curative treatment for locally advanced cervical cancer, radiotherapy is frequently undermined by radioresistant tumor cells that evade cell death and subsequently drive post-treatment tumor progression. This study aimed to identify candidate genes associated with radioresistance in cervical cancer and to explore their potential in predicting unfavorable outcomes among radioresistant patients, thereby providing a reference for future research. METHODS: We screened for co-expressed genes using transcriptomic data from radiation non-complete response (NCR) cervical cancer patients in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Cox regression analyses were conducted to identify the most significant radioresistance-associated genes for constructing a prognostic model. The predictive performance of this model was further validated through logistic regression, weighted gene co-expression network analysis (WGCNA), and pan-cancer analyses. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was performed to quantify the expression levels of key genes in cervical cancer tissue samples from radiosensitive and radioresistant patients. RESULTS: The resulting prognostic model comprised three genes: MTMR11, VANGL1, and CD46. This gene panel was significantly associated with the prognosis of cervical cancer patients receiving radiotherapy and showed acceptable predictive performance across multiple cancer types. qRT-PCR analysis revealed that the expression patterns of MTMR11 and VANGL1 were generally consistent with radioresistance of cervical cancer, whereas CD46 exhibited an unexpected expression trend. CONCLUSIONS: Our findings indicate that MTMR11, VANGL1, and CD46 are associated with radioresistance and prognosis in cervical cancer. Their potential clinical utility, especially in predicting radiotherapy response at the individual patient level, requires further validation in larger, independent, and prospective cohorts.

Cervical cancer↗

Cost-effective policies for cervical cancer screening. An international review.

Screening programmes for cervical cancer have been credited with reducing the incidence of and mortality from cervical cancer. The main components of these screening programmes are: (i) their level of organisation; (ii) the age at which women begin screening; (iii) the age at which women discontinue screening; (iv) the interval between repeat screens; (v) the frequency at which the programmes provide screening; and (vi) the response to an abnormal screening test. However, not all screening programmes are equally efficient and differences in programme components can result in big differences in their cost effectiveness. Studies that employ cost-effectiveness analysis (CEA) to examine the efficiency of different programme components can inform the development of cost-effective programmes. This article presents findings of an international review of cost-effectiveness studies of cervical cancer screening. These studies consistently find that certain types of programmes are more cost effective than others. Programmes that are centrally organised and implemented by the public sector are reported to be more cost effective than those that use public funds for screening at other medical visits (convenience screening), or those that provide guidelines for healthcare professionals and the public to promote spontaneous discretionary screening. There is also substantial agreement about the cost effectiveness of other programme components. When multiple screenings are possible, studies report that they should generally begin at age 25 to 35 years and end at age 65 to 70 years, although it is important that older women have 3 normal Papanicolaou (Pap) smears before the discontinuation of screening. The interval for repeat screens that is reported to provide the best balance between cost and life-years saved is between 3 and 5 years. However, when a choice must be made between screening more women fewer times, or screening fewer women more times, most studies indicate that it is more cost effective to prioritize resources to obtain at least one screening for each woman. The screening of previously unscreened and high-risk populations has been shown to be especially cost effective. Despite this agreement, many studies report that models of the cost effectiveness of screening for cervical cancer are sensitive to a number of parameters. Changes in the attendance rate of the programme, the quality of the Pap smear, and the cost of the Pap smear can markedly change the cost effectiveness of a screening programme. Finally, this review discusses different perspectives of social choice analysis (e.g. CEA and cost-benefit analysis), when the objective is to prevent cervical cancer and the options are to screen, detect and treat, to reduce behavioural risk factors, and/or to pursue promising biological research.

Cost-Benefit Analysis↗

Significant variation in performance does not reflect the effectiveness of the cervical cancer screening programme in Finland.

AIM: To characterise the variation in performance indicators of the Finnish cervical screening programme by screening laboratory and to assess whether the performance affects cervical cancer incidence. METHODS: Cervical cancer screening data from 1999 to 2003 from six well-established laboratories were used to analyse rates for follow-up recommendations, referrals and histologically confirmed dysplastic lesions. Laboratory-specific cervical cancer incidences for 1954-2003 were assessed using the cancer registry files. RESULTS: Differences in follow-up recommendations were up to 3.1-fold and 2.2-fold in referrals; differences in the rates for CIN1, CIN2 and CIN3+ were up to 4.5-, 4.7-, and 1.5-fold, respectively. Pre-screening incidence rates for cervical cancer varied 1.5-fold by laboratory, with no major differences in the incidence trends since the onset of screening. CONCLUSION: The performance of a cervical screening programme differs by screening laboratory but does not materially affect the overall programme effectiveness. This leads to variation in cost-effectiveness and probably in avoidable adverse effects. In cervical cancer screening studies, the outcome should be selected as closely as possible to the true measure of programme effectiveness, prevented invasive cervical cancers and subsequent deaths.

Adult↗

[Evaluation of mass screening for cervical cancer in Shiga Prefecture].

During 1969 and 1979 cervical cancer was found in 269 women out of a population of 166,202 who were attending mass screening for cervical cancer in Shiga Prefecture, Japan. The overall 0.162% detection rate for this disease in the mass screening was within the range reported from other prefectures in Japan. The peak prevalence of carcinoma in situ was found at ages 40 to 44 years, while invasive cancer was found evenly distributed between ages 35 and 54 years. Among 269 women with cervical cancer, 68.8% were found to have suspicious or positive smears at the time of the initial screening, and 94% were detected by the time of the third screening. Ten women with carcinoma in situ had received the screenings almost annually more than three times and were found to have suspicious or positive smears at the time of the fourth or fifth screening. Re-evaluation of previous smears in these patients revealed that 55.6% should have been diagnosed as positive smears. Also eight women with cervical cancer in stage Ia or Ib were initially found to have positive smears at the time of the second screening, and re-evaluation of their previous smears showed that 50% had been suspicious or positive smears at the initial screening. These findings indicate that annual repeat screenings for at least three years are necessary for the early detection of cervical cancer. It is also emphasized that laboratory quality and/or accuracy should be properly controlled to avoid false negative results.

Adult↗

"Pap" testing and hysterectomy prevalence: a survey of communities with high and low cervical cancer rates.

There is an inverse relation between cervical cancer rates and income in Los Angeles County communities, and there is a positive association between level of Papanicolaou (Pap) testing and income. Ethnic differences in cervical cancer rates and Pap testing are dependent on income. The relatively high rate of cervical cancer and low level of systematic screening in low income communities suggest that a community trial to assess the value of cytologic screening in reducing cervical cancer rates is feasible. Information on hysterectomy prevalence by type of procedure supports the idea that the long-observed decline in cervical cancer rates is in part attributable to a concomitant decrease in the ratio of subtotal to total hysterectomy.

Adult↗

Earlier diagnosis of cervical cancer. An analysis of reports to the California tumor registry from 1942 to 1963.

The mortality rate for cervical cancer in California declined during the period 1950-64. Indirect evidence shows that the incidence is also declining, but it is difficult to assess this decline because of the effect of the increasing use of cytologic examination on incidence rates for cervical cancer. Cervical cancer, in the 57 hospitals reporting to the California Tumor Registry, is being diagnosed at an earlier stage than in previous years. The proportion of cases diagnosed with the lesion still in the in situ stage rose from zero in 1942 to 56 per cent in 1963, and invasive cervical cancer, as a proportion of all invasive cancer in women, decreased from 15 per cent to 9 per cent. There is wide variation among hospitals in the proportion of cervical cancer cases that are in situ at time of diagnosis.

California↗

GATA2 promotes cervical cancer progression under the transcriptional activation of TRIP4.

The continued rise in recurrence and mortality rates of cervical cancer suggests the need to find novel therapeutic targets. Previous studies suggest that TRIP4 acts as a transcription factor to regulate cervical carcinogenesis and progression. Our aim was to explore whether the key downstream genes of TRIP4 functions same as TRIP4 in promoting cervical cancer development. We analyzed and confirmed the downstream targets of TRIP4 by RNA sequencing in cervical cancer cells with TRIP4 knockdown. The expression correlation between TRIP4 and GATA2 and the effect of GATA2 on cervical cancer cell growth were determined respectively by Western Blot, Scratch, Spheroid, and MTT analyses. Pulldown and ChIP experiments were performed to analyze the binding of TRIP4 to the promoter of GATA2. The clinical significance of GATA2 and TRIP4 expression in cervical cancer patients was analyzed by tissue microarray staining. GATA2 was highly expressed in cervical cancer tissues. Knockdown of GATA2 inhibited the growth, metastasis and stemness of cervical cancer cells and sensitized cervical cancer cells to radiation therapy. The inhibitory effect of TRIP4 knockdown on cervical cancer cells was rescued by GATA2 overexpression. Furthermore, TRIP4 could bind to the specific GATA2 promoter region, thereby activating its transcription. Clinical tissue microarray analysis indicated that the expression of TRIP4 and GATA2 was positively correlated, and high expression of both predicted a poor prognosis in cervical cancer patients. Our study demonstrated that GATA2 functions as the key downstream target of TRIP4 to promote cervical cancer progression and effective intervention of TRIP4/GATA2 signaling is expected to be developed as potential cervical cancer therapeutic strategy.

Humans↗

Genomic organization of human papillomavirus type 18 in cervical cancer specimens.

It has been reported that cervical cancers positive for human papillomavirus (HPV) 18 have a poorer prognosis than those with other HPV types. To gain a better understanding of the aggressive character of HPV 18-positive cancers, we examined the difference in genomic organization between HPV 18 and HPV 16 harbored in cervical cancers. We amplified E1 and E2 genes from 9 HPV 18-positive and 31 HPV 16-positive cervical cancers by polymerase chain reaction (PCR). At least one of the two early genes was missing in 3 out of 9 HPV 18-positive cancers, while both PCRs were positive in all 31 HPV 16-positive cancers (P < 0.05). We then analyzed the 9 HPV 18-positive cancers by 15 contiguous polymerase chain reactions covering collectively the whole HPV 18 genome. In addition to the three with a deletion of the E1 or E2 gene, one had a deletion in the E5 and L2 genes and one had an insertion in the long control region. The frequent alterations in genomic organization, especially preferential deletion of the E1 or E2 gene, may be related to the more aggressive properties of HPV 18-positive cervical cancers.

Adenocarcinoma↗

Expression of platelet derived growth factor family members and the potential role of imatinib mesylate for cervical cancer.

BACKGROUND: Despite significant achievements in the treatment of cervical cancer, it is still a deadly disease; hence newer therapeutical modalities are needed. Preliminary investigations suggest that platelet-derived growth factor (PDGF) might have a role in the development of cervical cancer, therefore it is important to determine whether this growth factor pathway is functional and its targeting with imatinib mesylate leads to growth inhibition of cervical cancer cells. RESULTS: PDGF receptors (PDGFR) and their ligands are frequently expressed in cervical cancer and the majority exhibited a combination of family members co-expression. A number of intronic and exonic variations but no known mutations in the coding sequence of the PDGFRalpha gene were found in cancer cell lines and primary tumors. Growth assays demonstrated that PDGFBB induces growth stimulation that can be blocked by imatinib and that this tyrosine kinase inhibitor on its own inhibits cell growth. These effects were associated with the phosphorylation status of the receptor. CONCLUSION: The PDGFR system may have a role in the pathogenesis of cervical cancer as their members are frequently expressed in this tumor and cervical cancer lines are growth inhibited by the PDGFR antagonist imatinib.

Journal Article↗

Prevalence and distribution of human papillomavirus type-16 DNA in pelvic lymph nodes of patients with cervical cancer and in women with no history of cervical abnormality.

The polymerase chain reaction (PCR) was used to investigate the prevalence and distribution of human papillomavirus (HPV)-16 DNA in paraffin sections of all pelvic lymph nodes removed from 14 patients with Stage Ib-cervical cancer at the time of resection of their primary tumours. The results were compared with those obtained from 8 women with no known history of cervical abnormality. In all, 22 cervical biopsies and 40 I lymph nodes (296 paraffin blocks) were examined. Nine of the 14 cervical cancer patients had primary tumours that were positive for HPV-16 DNA: only 3 of these had lymph nodes with histological evidence of metastasis, and HPV 16 DNA was detected in each of the corresponding paraffin blocks. HPV 16 DNA was also detected in varying proportions (8%-92%) of the histologically-negative lymph nodes from these women. There was no correlation between the HPV DNA-positive lymph nodes and their proximity to the primary tumour. HPV-16 DNA was not identified in any of the lymph nodes from the 5 women whose cancers were not HPV-16-related, or in those of women with no evidence of cervical abnormality. This preliminary survey suggests that HPV DNA is frequently transported from HPV-16-related cervical tumours to regional lymph nodes. However, its practical significance will not be clear until sufficient time has elapsed for correlation of the results with the clinical outcome.

Adult↗