Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment.

BACKGROUND: Pre-cancerous lesions of cervix (cervical intraepithelial neoplasia (CIN)) are usually treated with excisional or ablative procedures. In the UK, the National Health Service (NHS) cervical screening guidelines suggest that over 80% of treatments should be performed in an outpatient setting (colposcopy clinics). Furthermore, these guidelines suggest that analgesia should always be given prior to laser or excisional treatments. Currently various pain relief strategies are employed that may reduce pain during these procedures. OBJECTIVES: To assess whether the administration of pain relief (analgesia) reduces pain during colposcopy treatment and in the postoperative period. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2), MEDLINE (1950 to March week 3, 2016) and Embase (1980 to week 12, 2016) for studies of any design relating to analgesia for colposcopic management. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared all types of pain relief before, during or after outpatient treatment to the cervix, in women with CIN undergoing loop excision, laser ablation, laser excision or cryosurgery in an outpatient colposcopy clinic setting. DATA COLLECTION AND ANALYSIS: We independently assessed study eligibility, extracted data and assessed risk of bias. We entered data into Review Manager 5 and double checked it for accuracy. Where possible, we expressed results as mean pain score and standard error of the mean with 95% confidence intervals (CI) and synthesised data in a meta-analysis. MAIN RESULTS: We included 19 RCTs (1720 women) of varying methodological quality in the review. These trials compared a variety of interventions aimed at reducing pain in women who underwent treatment for CIN, including cervical injection with lignocaine alone, lignocaine with adrenaline, buffered lignocaine with adrenaline, prilocaine with felypressin, oral analgesics (non-steroidal anti-inflammatory drugs (NSAIDs)), inhalation analgesia (gas mixture of isoflurane and desflurane), lignocaine spray, cocaine spray, local application of benzocaine gel, lignocaine-prilocaine cream (EMLA cream) and transcutaneous electrical nerve stimulation (TENS).Most comparisons were restricted to single trial analyses and were under-powered to detect differences in pain scores between treatments that may or may not have been present. There was no difference in pain relief between women who received local anaesthetic infiltration (lignocaine 2%; administered as a paracervical or direct cervical injection) and a saline placebo (mean difference (MD) -13.74; 95% CI -34.32 to 6.83; 2 trials; 130 women; low quality evidence). However, when local anaesthetic was combined with a vasoconstrictor agent (one trial used lignocaine plus adrenaline while the second trial used prilocaine plus felypressin), there was less pain (on visual analogue scale (VAS)) compared with no treatment (MD -23.73; 95% CI -37.53 to -9.93; 2 trials; 95 women; low quality evidence). Comparing two preparations of local anaesthetic combined with vasoconstrictor, prilocaine plus felypressin did not differ from lignocaine plus adrenaline for its effect on pain control (MD -0.05; 95% CI -0.26 to 0.16; 1 trial; 200 women). Although the mean (± standard deviation (SD)) observed blood loss score was less with lignocaine plus adrenaline (1.33 ± 1.05) compared with prilocaine plus felypressin (1.74 ± 0.98), the difference was not clinically as the overall scores in both groups were low (MD 0.41; 95% CI 0.13 to 0.69; 1 trial; 200 women). Inhalation of gas mixture (isoflurane and desflurane) in addition to standard cervical injection with prilocaine plus felypressin resulted in less pain during the LLETZ (loop excision of the transformation zone) procedure (MD -7.20; 95% CI -12.45 to -1.95; 1 trial; 389 women). Lignocaine plus ornipressin resulted in less measured blood loss (MD -8.75 ml; 95% CI -10.43 to -7.07; 1 trial; 100 women) and a shorter duration of treatment (MD -7.72 minutes; 95% CI -8.49 to -6.95; 1 trial; 100 women) than cervical infiltration with lignocaine alone. Buffered solution (sodium bicarbonate buffer mixed with lignocaine plus adrenaline) was not superior to non-buffered solution of lignocaine plus adrenaline in relieving pain during the procedure (MD -8.00; 95% CI -17.57 to 1.57; 1 trial; 52 women).One meta-analysis found no difference in pain using VAS between women who received oral analgesic and women who received placebo (MD -3.51; 95% CI -10.03 to 3.01; 2 trials; 129 women; low quality evidence).Cocaine spray was associated with less pain (MD -28.00; 95% CI -37.86 to -18.14; 1 trial; 50 women) and blood loss (MD 0.04; 95% CI 0 to 0.70; 1 trial; 50 women) than placebo.None of the trials reported serious adverse events and majority of trials were at moderate or high risk of bias (13 trials). AUTHORS' CONCLUSIONS: Based on two small trials, there was no difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (MD -3.51; 95% CI -10.03 to 3.01; 129 women). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

Fertility and early pregnancy outcomes after conservative treatment for cervical intraepithelial neoplasia.

BACKGROUND: Cervical intra-epithelial neoplasia (CIN) typically occurs in young women of reproductive age. Although several studies have reported the impact that cervical conservative treatment may have on obstetric outcomes, there is much less evidence for fertility and early pregnancy outcomes. OBJECTIVES: To assess the effect of cervical treatment for CIN (excisional or ablative) on fertility and early pregnancy outcomes. SEARCH METHODS: We searched in January 2015 the following databases: the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library, Issue 12, 2014), MEDLINE (up to November week 3, 2014) and EMBASE (up to week 52, 2014). SELECTION CRITERIA: We included all studies reporting on fertility and early pregnancy outcomes (less than 24 weeks of gestation) in women with a history of CIN treatment (excisional or ablative) as compared to women that had not received treatment. DATA COLLECTION AND ANALYSIS: Studies were classified according to the treatment method used and the fertility or early pregnancy endpoint. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effects model and inter-study heterogeneity was assessed with I(2). Two review authors (MK, AM) independently assessed the eligibility of retrieved papers and risk of bias. The two review authors then compared their results and any disagreements were resolved by discussion. If still unresolved, a third review author (MA) was involved until consensus was reached. MAIN RESULTS: Fifteen studies (2,223,592 participants - 25,008 treated and 2,198,584 untreated) that fulfilled the inclusion criteria for this review were identified from the literature search. The meta-analysis demonstrated that treatment for CIN did not adversely affect the chances of conception. The overall pregnancy rate was higher for treated (43%) versus untreated women (38%; RR 1.29, 95% CI 1.02 to 1.64; 4 studies, 38,050 participants, very low quality), although the inter-study heterogeneity was considerable (P < 0.01). The pregnancy rates in treated and untreated women with an intention to conceive (88% versus 95%, RR 0.93, 95% CI 0.80 to 1.08; 2 studies, 70 participants, very low quality) and the number of women requiring more than 12 months to conceive (14% versus 9%, RR 1.45, 95% CI 0.89 to 2.37; 3 studies, 1348 participants, very low quality) were no different. Although the total miscarriage rate (4.6% versus 2.8%, RR 1.04, 95% CI 0.90 to 1.21; 10 studies, 39,504 participants, low quality) and first trimester miscarriage rate (9.8% versus 8.4%, RR 1.16, 95% CI 0.80 to 1.69, 4 studies, 1103 participants, low quality) was similar for treated and untreated women, CIN treatment was associated with an increased risk of second trimester miscarriage, (1.6% versus 0.4%, RR 2.60, 95% CI 1.45 to 4.67; 8 studies, 2,182,268 participants, low quality). The number of ectopic pregnancies (1.6% versus 0.8%, RR 1.89, 95% CI 1.50 to 2.39; 6 studies, 38,193 participants, low quality) and terminations (12.2% versus 7.4%, RR 1.71, 95% CI 1.31 to 2.22; 7 studies, 38,208 participants, low quality) were also higher in treated women.The results should be interpreted with caution. The included studies were often small with heterogenous design. Most of these studies were retrospective and of low or very low quality (GRADE assessment) and were therefore prone to bias. Subgroup analyses for the individual treatment methods and comparison groups and analysis to stratify for the cone length was not possible. AUTHORS' CONCLUSIONS: This meta-analysis suggests that treatment for CIN does not adversely affect fertility, although treatment was associated with an increased risk of miscarriage in the second trimester. These results should be interpreted with caution as the included studies were non-randomised and many were of low or very low quality and therefore at high risk of bias. Research should explore mechanisms that may explain the increase in mid-trimester miscarriage risk and stratify this impact of treatment by the length of the cone and the treatment method used.

Sentinel node assessment for diagnosis of groin lymph node involvement in vulval cancer.

BACKGROUND: Vulval cancer is usually treated by wide local excision with removal of groin lymph nodes (inguinofemoral lymphadenectomy) from one or both sides, depending on the tumour location. However, this procedure is associated with significant morbidity. As lymph node metastasis occurs in about 30% of women with early vulval cancer, accurate prediction of lymph node metastases could reduce the extent of surgery in many women, thereby reducing morbidity. Sentinel node assessment is a diagnostic technique that uses traceable agents to identify the spread of cancer cells to the lymph nodes draining affected tissue. Once the sentinel nodes are identified, they are removed and submitted to histological examination. This technique has been found to be useful in diagnosing the nodal involvement of other types of tumours. Sentinel node assessment in vulval cancer has been evaluated with various tracing agents. It is unclear which tracing agent or combination of agents is most accurate. OBJECTIVES: To assess the diagnostic test accuracy of various techniques using traceable agents for sentinel lymph node assessment to diagnose groin lymph node metastasis in women with FIGO stage IB or higher vulval cancer and to investigate sources of heterogeneity. SEARCH METHODS: We searched MEDLINE (1946 to February 2013), EMBASE (1974 to March 2013) and the relevant Cochrane trial registers. SELECTION CRITERIA: Studies that evaluated the diagnostic accuracy of traceable agents for sentinel node assessment (involving the identification of a sentinel node plus histological examination) compared with histological examination of removed groin lymph nodes following complete inguinofemoral lymphadenectomy (IFL) in women with vulval cancer, provided there were sufficient data for the construction of two-by-two tables. DATA COLLECTION AND ANALYSIS: Two authors (TAL, AP) independently screened titles and abstracts for relevance, classified studies for inclusion/exclusion and extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We used univariate meta-analytical methods to estimate pooled sensitivity estimates. MAIN RESULTS: We included 34 studies evaluating 1614 women and approximately 2396 groins. The overall methodological quality of included studies was moderate. The studies included in this review used the following traceable techniques to identify sentinel nodes in their participants: blue dye only (three studies), technetium only (eight studies), blue dye plus technetium combined (combined tests; 13 studies) and various inconsistent combinations of these three techniques (mixed tests; 10 studies). For studies of mixed tests, we obtained separate test data where possible.Most studies used haematoxylin and eosin (H&E) stains for the histological examination. Additionally an immunohistochemical (IHC) stain with and without ultrastaging was employed by 14 and eight studies, respectively. One study used reverse transcriptase polymerase chain reaction analysis (CA9 RT-PCR), whilst three studies did not describe the histological methods used.The pooled sensitivity estimate for studies using blue dye only was 0.94 (68 women; 95% confidence interval (CI) 0.69 to 0.99), for mixed tests was 0.91 (679 women; 95% CI 0.71 to 0.98), for technetium only was 0.93 (149 women; 95% CI 0.89 to 0.96) and for combined tests was 0.95 (390 women; 95% CI 0.89 to 0.97). Negative predictive values (NPVs) for all index tests were > 95%. Most studies also reported sentinel node detection rates (the ability of the test to identify a sentinel node) of the index test. The mean detection rate for blue dye alone was 82%, compared with 95%, 96% and 98% for mixed tests, technetium only and combined tests, respectively. We estimated the clinical consequences of the various tests for 100 women undergoing the sentinel node procedure, assuming the prevalence of groin metastases to be 30%. For the combined or technetium only tests, one and two women with groin metastases might be 'missed', respectively (95% CI 1 to 3); and for mixed tests, three women with groin metastases might be 'missed' (95% CI 1 to 9). The wide CIs associated with the pooled sensitivity estimates for blue dye and mixed tests increased the potential for these tests to 'miss' women with groin metastases. AUTHORS' CONCLUSIONS: There is little difference in diagnostic test accuracy between the technetium and combined tests. The combined test may reduce the number of women with 'missed' groin node metastases compared with technetium only. Blue dye alone may be associated with more 'missed' cases compared with tests using technetium. Sentinel node assessment with technetium-based tests will reduce the need for IFL by 70% in women with early vulval cancer. It is not yet clear how the survival of women with negative sentinel nodes compares to those undergoing standard surgery (IFL). A randomised controlled trial of sentinel node dissection and IFL has methodological and ethical issues, therefore more observational data on the survival of women with early vulval cancer are needed.

Interventions for preventing blood loss during the treatment of cervical intraepithelial neoplasia.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) is the most common pre-malignant lesion. Surgical treatments for CIN are commonly associated with blood loss. OBJECTIVES: To assess the effectiveness and safety of interventions for preventing blood loss during the treatment of CIN. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE and CENTRAL up to November 2012. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of vasopressin, tranexamic acid, haemostatic sutures, Amino-Cerv or Monsel's solution in women undergoing surgery for CIN. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data and assessed risk of bias. Risk ratios comparing adverse events in women who received one of the interventions were pooled in a random-effects meta-analyses or included in single trial analyses. MAIN RESULTS: Twelve RCTs (N = 1602, of whom 1512 were assessed) were included.Vasopressin significantly reduced perioperative bleeding (mean difference (MD) = -100.80, 95% confidence interval (CI) -129.48 to -72.12) and was associated with a decreased risk of bleeding that required haemostatic sutures or further vasopressin, compared to placebo (risk ratio (RR) = 0.39, 95% CI 0.27 to 0.56).Tranexamic acid significantly reduced risk of secondary haemorrhage (RR = 0.23, 95% CI 0.11 to 0.50), but not primary haemorrhage (RR = 1.24, 95% CI 0.04 to 38.23) after knife and laser cone biopsy, compared with placebo. There was also a statistically significant reduction in postoperative blood loss compared with placebo (MD = -55.60, 95% CI -94.91 to -16.29).Packing with Monsel's solution resulted in less perioperative blood loss (MD = -22.00, 95% CI -23.09 to -20.91) and decreased the risk of dysmenorrhoea (RR = 0.37, 95% CI 0.16 to 0.84), unsatisfactory colposcopy (RR = 0.43, 95% CI 0.30 to 0.63) and cervical stenosis (RR = 0.35, 95% CI 0.25 to 0.49) compared to routine suturing, but was not statistically different to sutures for risk of primary and secondary haemorrhages.Amino-Cerv antibiotic gel failed to make a difference on secondary haemorrhage but was associated with significantly less vaginal discharge at 2 weeks compared with routine care (RR = 0.27, 95% CI 0.09 to 0.86).There was no significant difference in blood loss between women who received ball electrode diathermy and those who received Monsel's paste (MD = 4.82, 95% CI -3.45 to 13.09). AUTHORS' CONCLUSIONS: Bleeding associated with surgery of the cervix appears to be reduced by vasopressin, used in combination with local anaesthetic. Tranexamic acid appears to be beneficial after knife and laser cone biopsy. There are insufficient data to assess the effects on primary haemorrhage. There is some evidence that haemostatic suturing has an adverse effect on blood loss, cervical stenosis and satisfactory colposcopy.

Surgery for cervical intraepithelial neoplasia.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) is the most common pre-malignant lesion. Atypical squamous changes occur in the transformation zone of the cervix with mild, moderate or severe changes described by their depth (CIN 1, 2 or 3). Cervical intraepithelial neoplasia is treated by local ablation or lower morbidity excision techniques. Choice of treatment depends on the grade and extent of the disease. OBJECTIVES: To assess the effectiveness and safety of alternative surgical treatments for CIN. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE and EMBASE (up to November 2012). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of alternative surgical treatments in women with cervical intraepithelial neoplasia. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risks of bias. Risk ratios that compared residual disease after the follow-up examination and adverse events in women who received one of either laser ablation, laser conisation, large loop excision of the transformation zone (LLETZ), knife conisation or cryotherapy were pooled in random-effects model meta-analyses. MAIN RESULTS: Twenty-nine trials were included. Seven surgical techniques were tested in various comparisons. No significant differences in treatment failures were demonstrated in terms of persistent disease after treatment. Large loop excision of the transformation zone appeared to provide the most reliable specimens for histology with the least morbidity. Morbidity was lower than with laser conisation, although the trials did not provide data for every outcome measure. There were not enough data to assess the effect on morbidity when compared with laser ablation. AUTHORS' CONCLUSIONS: The evidence suggests that there is no obvious superior surgical technique for treating cervical intraepithelial neoplasia in terms of treatment failures or operative morbidity.

Human papillomavirus testing versus repeat cytology for triage of minor cytological cervical lesions.

BACKGROUND: Atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intra-epithelial lesions (LSIL) are minor lesions of the cervical epithelium, detectable by cytological examination of cells collected from the surface of the cervix of a woman.Usually, women with ASCUS and LSIL do not have cervical (pre-) cancer, however a substantial proportion of them do have underlying high-grade cervical intra-epithelial neoplasia (CIN, grade 2 or 3) and so are at increased risk for developing cervical cancer. Therefore, accurate triage of women with ASCUS or LSIL is required to identify those who need further management.This review evaluates two ways to triage women with ASCUS or LSIL: repeating the cytological test, and DNA testing for high-risk types of the human papillomavirus (hrHPV) - the main causal factor of cervical cancer. OBJECTIVES: Main objective To compare the accuracy of hrHPV testing with the Hybrid Capture 2 (HC2) assay against that of repeat cytology for detection of underlying cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) or grade 3 or worse (CIN3+) in women with ASCUS or LSIL. For the HC2 assay, a positive result was defined as proposed by the manufacturer. For repeat cytology, different cut-offs were used to define positivity: Atypical squamous cells of undetermined significance or worse (ASCUS+), low-grade squamous intra-epithelial lesions or worse (LSIL+) or high-grade squamous intra-epithelial lesions or worse (HSIL+).Secondary objective To assess the accuracy of the HC2 assay to detect CIN2+ or CIN3+ in women with ASCUS or LSIL in a larger group of reports of studies that applied hrHPV testing and the reference standard (coloscopy and biopsy), irrespective whether or not repeat cytology was done. SEARCH METHODS: We made a comprehensive literature search that included the Cochrane Register of Diagnostic Test Accuracy Studies; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE (through PubMed), and EMBASE (last search 6 January 2011). Selected journals likely to contain relevant papers were handsearched from 1992 to 2010 (December). We also searched CERVIX, the bibliographic database of the Unit of Cancer Epidemiology at the Scientific Institute of Public Health (Brussels, Belgium) which contains more than 20,000 references on cervical cancer.More recent searches, up to December 2012, targeted reports on the accuracy of triage of ASCUS or LSIL with other HPV DNA assays, or HPV RNA assays and other molecular markers. These searches will be used for new Cochrane reviews as well as for updates of the current review. SELECTION CRITERIA: Studies eligible for inclusion in the review had to include: women presenting with a cervical cytology result of ASCUS or LSIL, who had undergone both HC2 testing and repeat cytology, or HC2 testing alone, and were subsequently subjected to reference standard verification with colposcopy and colposcopy-directed biopsies for histologic verification. DATA COLLECTION AND ANALYSIS: The review authors independently extracted data from the selected studies, and obtained additional data from report authors.Two groups of meta-analyses were performed: group I concerned triage of women with ASCUS, group II concerned women with LSIL. The bivariate model (METADAS-macro in SAS) was used to assess the absolute accuracy of the triage tests in both groups as well as the differences in accuracy between the triage tests. MAIN RESULTS: The pooled sensitivity of HC2 was significantly higher than that of repeat cytology at cut-off ASCUS+ to detect CIN2+ in both triage of ASCUS and LSIL (relative sensitivity of 1.27 (95% CI 1.16 to 1.39; P value < 0.0001) and 1.23 (95% CI 1.06 to 1.4; P value 0.007), respectively. In ASCUS triage, the pooled specificity of the triage methods did not differ significantly from each other (relative specificity: 0.99 (95% CI 0.97 to 1.03; P value 0.98)). However, the specificity of HC2 was substantially, and significantly, lower than that of repeat cytology in the triage of LSIL (relative specificity: 0.66 (95% CI 0.58 to 0.75) P value < 0.0001). AUTHORS' CONCLUSIONS: HPV-triage with HC2 can be recommended to triage women with ASCUS because it has higher accuracy (significantly higher sensitivity, and similar specificity) than repeat cytology. When triaging women with LSIL, an HC2 test yields a significantly higher sensitivity, but a significantly lower specificity, compared to a repeat cytology. Therefore, practice recommendations for management of women with LSIL should be balanced, taking local circumstances into account.

Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment.

BACKGROUND: Pre-cancerous lesions of cervix (cervical intraepithelial neoplasia (CIN)) are usually treated with excisional or ablative procedures. In the UK, the NHS cervical screening guidelines suggest that over 80% of treatments should be performed in an outpatient setting (colposcopy clinics). Furthermore, these guidelines suggest that analgesia should always be given prior to laser or excisional treatments. Currently various pain relief strategies are employed that may reduce pain during these procedures. OBJECTIVES: The aim of this review was to assess whether the administration of pain relief reduced pain during colposcopy treatment and in the postoperative period. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Review Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL - May 2011) (2011, Issue 2), MEDLINE (1950 to May week 2, 2011), EMBASE (1980 to week 20, 2011) for studies of any design relating to analgesia for colposcopic management. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared all types of pain relief before, during or after outpatient treatment to the cervix, in adult women with CIN undergoing loop excision, laser ablation, laser excision or cryosurgery in an outpatient colposcopy clinic setting. DATA COLLECTION AND ANALYSIS: We independently assessed study eligibility, extracted data and assessed risk of bias. We entered data into RevMan and double checked it for accuracy. Where possible, the results were expressed as mean pain score and standard error of the mean with 95% confidence intervals (CI) and the data were synthesised in a meta-analysis. MAIN RESULTS: We included 17 RCTs (1567 women) of varying methodological quality in the review. These trials compared a variety of interventions aimed at reducing pain in women who underwent treatment for CIN, including cervical injection with lignocaine alone, lignocaine with adrenaline, prilocaine with felypressin, oral analgesics (non-steroidal anti-inflammatory drugs (NSAIDs)), inhalation analgesia (gas mixture of isoflurane and desflurane), lignocaine spray, cocaine spray, local application of benzocaine gel, lignocaine-prilocaine cream (EMLA cream) and transcutaneous electrical nerve stimulation (TENS).Most comparisons were restricted to single trial analyses and were under-powered to detect differences in pain scores between treatments that may or may not have been present. There was no significant difference in pain relief between women who received local anaesthetic infiltration (lignocaine 2%; administered as a paracervical or direct cervical injection) and a saline placebo (2 trials; 130 women; MD -13.74; 95% CI -34.32 to 6.83). However, when local anaesthetic was combined with a vasoconstrictor agent (one trial used lignocaine combined with adrenaline while the second trial used prilocaine combined with felypressin), significantly less pain (on visual analogue scores) occurred compared with no treatment (2 trials; 95 women; MD -23.73; 95% CI -37.53 to -9.93). Comparing two preparations of local anaesthetic plus vasoconstrictor, prilocaine combined with felypressin did not differ from lignocaine combined with adrenaline for its effect on pain control (1 trial; 200 women; MD -0.05; 95% CI -0.26 to 0.16). Although the mean observed blood loss score was less with lignocaine plus adrenaline (1.33 ± 1.05) as compared with prilocaine plus felypressin (1.74 ± 0.98), the difference was not clinically significant as the overall scores in both groups were low (1 trial; 200 women; MD 0.41; 95% CI 0.13 to 0.69). Inhalation of gas mixture (isoflurane and desflurane) in addition to standard cervical injection with prilocaine plus felypressin resulted in significantly less pain during the LLETZ (loop excision of the transformation zone) procedure (1 trial; 389 women; MD -7.20; 95% CI -12.45 to -1.95). Lignocaine plus ornipressin resulted in significantly less measured blood loss (1 trial; 100 women; MD -8.75; 95% CI -10.43 to -7.07) and a shorter duration of treatment (1 trial; 100 women; MD -7.72; 95% CI -8.49 to -6.95) than cervical infiltration with lignocaine alone.One meta-analysis found no statistically significant difference in pain using visual analogue scores between women who received oral analgesic and those who received placebo (2 trials; 129 women; MD -3.51; 95% CI -10.03 to 3.01; Analysis 6.1).Cocaine spray was associated with significantly less pain (1 trial; 50 women; MD -28; 95% CI -37.86 to -18.14) and blood loss (1 trial; 50 women; MD 0.04; 95% CI 0 to 0.70) than placebo.No serious adverse events were reported in any of the trials and majority of trials were at moderate or high risk of bias (n = 12). AUTHORS' CONCLUSIONS: Based on two small trials, there was no significant difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (129 women; MD -3.51; 95% CI -10.03 to 3.01). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high-quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.