Value of high-risk human papillomavirus 16 deoxyribonucleic acid testing with cytological entities in peri and postmenopausal women.

BACKGROUND: Genital human papillomavirus (HPV) infection is a sexually transmitted disease that is caused by HPV. Some types of HPV, called high-risk (HR) types may cause cell changes that sometimes lead to cervical cancer. HPV screening has been proposed for symptomatic female population; however, Pap test is the main stay in low resource setting. AIM: To detect HR HPV 16 positivity in perimenopausal and postmenopausal women and its association with cytological entities diagnosed on Pap smear. MATERIALS AND METHODS: Pap smears and cervical scrapes were collected from 230 women consisting of 120 perimenopausal women approaching menopause and 110 postmenopausal women with a cervix after cessation of menstruation and processed as per routine procedure for detection of HR-HPV 16 deoxyribonucleic acid (DNA). Cytologically abnormal HPV 16 negative cases were also tested for other HR-HPV types. RESULTS: Among the perimenopausal women 12 (10%) cases were positive for HR-HPV 16 consisting of 6 (5%) abnormal cases and 108 (90%) were HPV 16 negative consisting of 5 (4.1%) abnormal cases. However, among 110 postmenopausal women 14 (12.7%) were positive for HPV 16 DNA consisting of 6 (5.4%) abnormal cases and 96 (87.2%) were HPV 16 negative consisting of 4 (3.6%) abnormal cases. HPV 16 negative abnormal cases (9) were positive for low risk-HPV 6/11 consisting of atypical squamous cells (3) and low-grade squamous intraepithelial lesions-HPV (6). CONCLUSIONS: There is not much variation in HPV 16 positive cases in peri and postmenopausal women. By combining HPV DNA testing with Pap smear more cases having potential for pre-cancer lesions may be detected; however, HPV test cannot replace the Pap smear in low resource setting.

Defining the validity of classical and non-classical cellular changes indicative of low-grade squamous intraepithelial lesion encompassing human papillomavirus infection in relation to human papillomavirus deoxyribonucleic acid testing.

BACKGROUND: Human papillomavirus (HPV) infection as of now has been beyond doubt to be the causative agent for cervical carcinoma. Its morphological identification in Pap smear is important. AIM: To define the validity of classical and non-classical cellular changes indicative of low-grade squamous intraepithelial lesion (SIL) encompassing HPV infection in relation to positivity for 'high risk' HPV16 as well as for 'low risk' HPV6/11. MATERIALS AND METHODS: A total of 3000 Papanicolaou smears were screened, of which 150 were reported as low grade-SIL encompassing HPV infection (LSIL-HPV). Subsequently cervical scrapes from these 150 subjects, along with equal number of normal women as controls, were collected and processed for HPV deoxy-ribonucleic acid testing by polymerase chain reaction (PCR). RESULTS: ON THE BASIS OF CYTOMORPHOLOGICAL CHARACTERISTICS IN PAP SMEARS, HPV INFECTION WERE CATEGORIZED INTO THE FOLLOWING TWO GROUPS: Classical (koilocytic) changes (CC) encountered in 30 women and non-classical changes (NCC) encountered in 120 women. It was observed that 21 (70%) CC and 46 (38.3%) NCC of HPV infection were positive for HR-HPV16; however only 12 cases (10%) of NCC and two cases (6.6%) of CC were positive for LR-HPV 6/11. Majority (41.7%) of HPV positive cases were reported in the age group of 25 to 30 years and HPV positivity decreased with the increasing age. CONCLUSION: Classical cellular changes are not the only diagnostic features for HPV infection in Pap smear, non-classical diagnostic features also support the diagnosis of HPV infection and may be positive for HR-HPV16.

Incidence and cytomorphological peculiarities of lower genital tract infections in vault (post hysterectomy) smears versus pap smears from non-hysterectomy subjects: a retrospective study.

OBJECTIVE: To evaluate morphology and frequency of lower genital infections in (post hysterectomy) vault smears of women. METHODS: We analyzed vault smears from 500 women who had undergone hysterectomy, either for benign diseases (230) or for carcinoma cervix (270) and findings were compared with Pap smear diagnosis of non-hysterectomy subjects. RESULTS: Majority 432/500 (87%) of the vault smears were negative for squamous abnormality in comparison to 381/500 (76%) Pap smears from non-hysterectomy subjects. It was observed that 48 (9.6%) vault smears showed lower genital tract infections, however frequency of infections was reported significantly higher 101 (20.2%) in non-hysterectomy subjects. Gardenerella vaginalis was the leading infection in vault smears 26 (5.2%) due to benign diseases and was prevalent in the fifth and sixth decades of life of women in comparison to 43 (8.2%) in Pap smears with higher prevalence in the fourth decade of life. Trichomonas vaginalis and Human Papillomavirus infection were the second commonest infections in vault smears followed by Candida albicans. CONCLUSION: Cytologically diagnosed gynecological infections were remarkably low 48 (9.6%) in vault smears as compared to 101/500 (20.2%) amongst non-hysterectomy subjects. Infections which mainly thrive at the Squamo-columnar junction i.e. HPV, Chlamydia and HSV were absent or rare in vault smears. Further incidence of infections in the vault smears where hysterectomy was done due to carcinoma cervix was as low as 10 (3.7%) as compared to 38 (16.5%) where hysterectomy was done due to benign uterine diseases.

Elimination of high-risk human papillomavirus type HPV16 infection by 'Praneem' polyherbal tablet in women with early cervical intraepithelial lesions.

PURPOSE: 'Praneem', a polyherbal formulation developed by us, has successfully completed Phase II efficacy study for treatment of abnormal vaginal discharge due to reproductive tract infections that act as co-factors for HPV persistence. In the present study we evaluated potential anti-HPV activity of Praneem in women infected with high risk HPV type 16. METHODS: Twenty women molecularly diagnosed positive for HPV16 infection without or with low grade squamous intraepithelial lesion (LSIL) or inflammation were assigned to receive intra-vaginal, topical application of either Praneem tablet or placebo for 30 days excluding the days of menstrual period and were evaluated for persistence of HPV infection using HPV L1 consensus and HPV type 16-specific PCR as primary outcome. RESULTS: One course of Praneem treatment resulted in elimination of HPV in 6 out of 10 (60%) cases. A repeat treatment of four patients with persisting HPV infection resulted in clearance of HPV in two additional cases resulting in an overall 80% clearance of HPV 16 as against a spontaneous clearance of 10% (1/10) seen in the placebo arm. The elimination of HPV DNA was found to be accompanied by marked improvement in clinical symptoms and cytological abnormalities of Praneem-treated patients. CONCLUSION: Our results showed for the first time that a 30-day intra-vaginal application of the Praneem can result in elimination of HPV infection from the uterine cervix.

Effect of aberrant promoter methylation of FHIT and RASSF1A genes on susceptibility to cervical cancer in a North Indian population.

As current evidence suggests the involvement of epigenetic modification of tumour suppressor genes in human cancer, we investigated the aberrant promoter methylation of FHIT and RASSF1A genes in human papillomavirus (HPV)-mediated cervical cancer in Indian women. We analysed 60 cervical cancer tissue biopsies of different clinical stage and histological grading and 23 healthy control samples with normal cervical cytology. Methylation-specific polymerase chain reaction (MSP) was performed to analyse the methylation status of FHIT and RASSF1A genes and confirmed by sequencing. Both patients and controls were screened for HPV infection and 98% of the HPV-infected cases showed positivity for HPV type 16. Aberrant promoter methylation of the FHIT gene was found in 28.3% (17/60) of cases and of the RASSF1A gene in 35.0% (21/60) of cases; promoter methylation of both the genes was found in 13.3% (8/60) of cervical cancer cases. Methylation was significantly (p<0.01) associated with the cervical cancer cases compared with controls. None of the 23 controls was found to be methylated in either of these genes. This is the first study indicating a correlation between the promoter methylation of FHIT and RASSF1A genes and the clinical stage and histological grading of cervical carcinoma in Indian women. Future studies are underway to examine the practical implications of these findings for use as a biomarker.