Justine M. Ritchie

Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers.

There are few well‐established patient risk factors associated with human papillomavirus (HPV) infection in cancers of the oral cavity and oropharynx. The purpose of this study was to determine if there were significant different risk factors and tumor characteristics between HPV‐positive and HPV‐negative cancer cases. HPV was evaluated in cancer tissue and exfoliated oral cells of 193 oral cavity/oropharynx cancer patients using PCR and direct DNA sequencing. A patient questionnaire collected information about risk factors, sexual practices and medical history. The prevalence of HPV high‐risk (HR) types was 20% in cancer cases. Three types were identified: HPV‐16 (87%), HPV‐18 (3%) and HPV‐33 (11%). Risk factors for HPV‐HR included younger age (≤ 55 years vs. > 55 years; adjusted OR = 3.4; 95% CI = 1.6–7.3) and younger‐age cases who had more lifetime sex partners (adjusted OR = 3.8; 95% CI = 1.4–10.1), practiced oral‐genital sex (adjusted OR = 4.3; 95% CI = 1.8–10.4) or oral‐anal sex (adjusted OR = 19.5; 95% CI = 3.4–113). Compared to HPV‐negative cancers, HPV‐HR cancers were more likely to have a positive HPV‐HR exfoliated oral cytology test (adjusted OR = 7.8; 95% CI = 3.4–18.4), later stage (adjusted OR = 3.0), nodal involvement (adjusted OR = 4.1) and advanced grade (adjusted OR = 3.0). This study shows new evidence that the prevalence of oncogenic mucosal HPV is higher in younger‐age oral cavity/oropharynx cancer cases whose sexual practices are typically associated with sexual transmission of the virus. HPV detection also appears to be an indicator of advanced disease characteristics that may require different clinical treatment for this subset of patients. An exfoliated oral cytology test for HPV was a significant predictor of HR types in the cancers, suggesting that an oral rinse may provide an early biomarker of infected tumors.

Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx

Although studies have established human papillomaviruses (HPVs) as a risk factor for oral and oropharyngeal cancer, it is not clear whether viral infection affects survival in head and neck malignancies. This investigation examined the relationship between HPV and survival in carcinomas of the oral cavity and oropharynx. Formalin‐fixed, paraffin‐embedded tumor specimens from 139 newly diagnosed cases were tested for HPVs by PCR and DNA sequencing. Patient and tumor characteristics were obtained from questionnaires, pathology reports and cancer registries. Odds ratios (ORs) and relative risks (RRs) were based on logistic and Cox regression models, respectively. HPVs were detected in 21% of the tumors; 83% were HPV‐16. Greater risk of HPV infection was associated with males (OR = 2.9, 95% CI = 1.0–8.6), a history of oral‐genital sex (OR = 4.2, 95% CI = 1.5–11.7), and oropharyngeal tumors (OR = 10.4, 95% CI = 3.5–31.2). As tobacco usage increased, the odds of HPV detection decreased (OR = 0.97/pack‐year, 95% CI = 0.96–0.99). HPV infected patients had better overall survival (RR = 0.3, 95% CI = 0.1–0.8) than those with HPV‐negative tumors. There was an interaction between gender and HPV for overall (p = 0.05) and disease‐specific (p = 0.03) survival that suggested that HPV infected males had better prognosis than HPV‐negative males, but this was not the case among females. HPV status was identified as an independent prognostic factor in oral and oropharyngeal cancers. This result appeared to be gender‐specific, suggesting the need for further study of the interaction between HPV and gender on survival.

Response Assessment of Aggressive Non-Hodgkin’s Lymphoma by Integrated International Workshop Criteria and Fluorine-18–Fluorodeoxyglucose Positron Emission Tomography

PURPOSE To determine whether a response classification based on integration of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) into the International Workshop Criteria (IWC) provides a more accurate response assessment than IWC alone in patients with non-Hodgkins lymphoma (NHL). PATIENTS AND METHODS Fifty-four patients with aggressive NHL who underwent FDG-PET and computed tomography 1 to 16 weeks after four to eight cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone were assessed for complete response (CR), unconfirmed CR (CRu), partial response (PR), stable disease (SD), and progressive disease (PD) by the IWC and by integrated IWC and FDG-PET (IWC+PET). Progression-free survival (PFS) was also compared between IWC- and IWC+PET-assigned response designations. RESULTS By IWC, 17 patients had a CR, seven had a CRu, 19 had a PR, nine had SD, and two had PD. In comparison, by IWC+PET, 35 patients had a CR, 12 had a PR, six had SD, one had PD, and zero had a CRu. In separate multivariate models, PFS was significantly shorter in patients with PR than in those with a CR using IWC (hazard ratio [HR], 8.9; P = .021) or IWC+PET (HR, 29.7; P = .0003). However, when the two classifications were included in the same multivariate model, only IWC+PET was a statistically significant independent predictor for PFS (P = .008 v P = .72 for IWC). In addition, when patients with a PR by IWC and a CR by IWC+PET were compared with those with a CR by IWC and a CR by IWC+PET, there was no significant difference in PFS (HR, 1.6; P = .72), indicating that IWC+PET identified a subset of IWC-PR patients with a more favorable prognosis. CONCLUSION Compared with IWC, the IWC+PET-based assessment provides a more accurate response classification in patients with aggressive NHL.

Social Support, Psychological Distress, and Natural Killer Cell Activity in Ovarian Cancer

PURPOSE Psychosocial stress has been related to impaired immunity in cancer patients. However, the extent to which these relationships exist in immune cells in the tumor microenvironment in humans has not been explored. We examined relationships among distress, social support, and natural killer (NK) cell activity in ovarian cancer patients in peripheral-blood mononuclear cells (PBMC), ascitic fluid, and tumor-infiltrating lymphocytes (TIL). PATIENTS AND METHODS Patients awaiting surgery for a pelvic mass suspected of being ovarian cancer completed psychological questionnaires and gave a presurgical sample of peripheral blood. Samples of tumor and ascites were taken during surgery, lymphocytes were then isolated, and NK cytotoxicity and percentage were determined. The final sample, which was confirmed by surgical diagnosis, included 42 patients with epithelial ovarian cancer and 23 patients with benign masses. RESULTS Peripheral NK cell activity was significantly lower among ovarian cancer patients than in patients with benign masses. Among ovarian cancer patients, NK cytotoxicity in TIL was significantly lower than in PBMC or ascitic fluid. Social support was related to higher NK cytotoxicity in PBMC and TIL, adjusting for stage. Distress was related to lower NK cytotoxicity in TIL. A multivariate model indicated independent associations of both distress and social support with NK cell activity in TIL. CONCLUSION Psychosocial factors, such as social support and distress, are associated with changes in the cellular immune response, not only in peripheral blood, but also at the tumor level. These relationships were more robust in TIL. These findings support the presence of stress influences in the tumor microenvironment.

PREOPERATIVE CA 125 LEVELS: AN INDEPENDENT PROGNOSTIC FACTOR FOR EPITHELIAL OVARIAN CANCER

OBJECTIVE To estimate the association of preoperative CA 125 levels with outcome in primary ovarian cancer patients. METHODS One hundred forty‐two patients with epithelial ovarian cancer, who had a serum CA 125 level drawn before surgery, were retrospectively evaluated. The relationship of preoperative CA 125 levels and various preoperative and postoperative variables was evaluated. CA 125 levels were determined using a solid‐phase immunoassay. RESULTS The median CA 125 value for all patients was 582 U/mL (range 7–52,930 U/mL). Preoperative CA 125 values did not correlate with increasing age (P = .40), but were found to be significantly associated with serous histology compared with other histology (median CA 125 of 870 versus 334 U/mL, P = .02), high‐stage (III/IV) compared with low‐stage (median CA 125 of 893 versus 174 U/mL, P < .001), high tumor grade (3) compared with grade 1 or 2 (median CA 125 of 928 versus 323 U/mL, P < .001), and the presence of ascites compared with absence of ascites (median CA 125 of 893 versus 220 U/mL, P < .001). Suboptimal cytoreduction (more than 1 cm residual) was associated with significantly higher CA 125 levels (1067 U/mL) compared with individuals with optimal cytoreduction (399 U/mL, P < .001). Preoperative CA 125 values less than 500 U/mL had a positive predictive value for optimal cytoreduction of 82%, but a poor negative predictive value of 48%. After adjusting for covariates, there was a significant association between CA 125 levels and disease‐specific survival. As preoperative CA 125 levels increased, the risk of death increased except at the highest values of CA 125. CONCLUSION Preoperative CA 125 is an independent risk factor for death due to disease in ovarian cancer, but not a reliable predictor of optimal cytoreduction.

Prevalence of human papillomavirus in the oral cavity/oropharynx in a large population of children and adolescents.

Objective: Human papillomavirus (HPV) in the oral cavity or oropharynx is associated with an increased risk of laryngeal papillomatosis, head and neck cancer, and cervical and other genital cancers. We evaluated the prevalence of HPV DNA in the oral cavity/oropharynx in a cross section of children aged 2 weeks to 20 years. Methods: A risk factor questionnaire and oral exfoliated cells were collected from children (N = 1235). HPV DNA was detected using PCR, dot blot hybridization, and DNA sequencing. Results: The HPV prevalence was 1.9% in the oral cavity/oropharynx of children. A bimodal age distribution was observed with the highest HPV prevalence in the youngest and oldest groups: 2.5% aged <1 year, 0.8% aged 1 to 4 years, 1.2% aged 5 to 11 years, 1.5% in aged 12 to 15 years, and 3.3% in aged 16 to 20 years. The prevalence of the HPV quadrivalent vaccine types (HPV-6, 11, 16, 18) reached 0.9% in the 16- to 20-year age group. In this age group, female gender [odds ratio (OR): 6.9, P = 0.04], genital warts (OR: 19.3, P < 0.01), and current smoker (OR: 6.5, P = 0.01) were associated with a higher risk of being detected with an oral HPV infection. No risk factors in parents were identified with transmission of HPV to infants. Conclusions: The age-specific prevalence rates of HPV in this large cross section of children and adolescents demonstrate that HPV infection is acquired gradually in childhood. These data support a target age for HPV vaccination before puberty to prevent serious HPV-related genital and oral diseases.

Quality of life and mood in women with gynecologic cancer: A one year prospective study

Quality of life (QOL) and mood were prospectively investigated during the first year of treatment among women with gynecologic cancers. Relationships of coping styles to QOL and mood were examined.

Organochlorines and Risk of Prostate Cancer

This pilot study examined the relationships of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) with prostate cancer. Ninety-nine controls were frequency matched by age in 5-year increments to 58 prostate cancer patients. Thirty PCBs and 18 OCPs were measured in serum by gas chromatography. Multiple logistic regression was used to assess the magnitude of association. Seven organochlorines, dieldrin, p,p′-DDE, trans-nonachlor, oxychlordane, heptachlor epoxide, and PCBs 153 and 180 were detected in at least 20% of all study participants. Adjusting for age, body mass index, and a history of prostatitis, oxychlordane and PCB 180 were associated with an increased risk of prostate cancer. This study suggests that long-term, low-dose exposure to specific OCPs and PCBs in the general population may contribute to an increased risk of prostate cancer and supports further investigation in this area.

Efficacy of beta-lapachone in pancreatic cancer treatment: exploiting the novel, therapeutic target NQO1.

NAD(P)H:quinone oxidoreductase (NQO1) is elevated in human pancreatic cancers. We hypothesized that £]-lapachone, a novel 1,2-naphthoquinone with potential antitumor activity in cancer cells expressing elevated levels of NQO1, would induce cytotoxicity in pancreatic cancer cells, wherein this two-electron reductase was recently found elevated. ?-lapachone decreased clonogenic cell survival, metabolic cell viability, and anchorage-independent growth in soft agar. The cytotoxic in vitro effects of ?- lapachone were inhibited with co-administration of dicumarol, a specific inhibitor of NQO1. In pre-established human pancreatic tumor xenografts in nude mice, ?-lapachone demonstrated greater tumor growth inhibition when given intratumorally compared to when complexed with cyclodextrin to increase its bioavailability. Due to the poor prognosis of patients with pancreatic cancer and the limited effectiveness of surgery, chemotherapy, and radiation therapy, treatment regimens based on sound, tumor-specific rationales are desperately need for this disease.

Human papillomavirus prevalence and types in newborns and parents: concordance and modes of transmission.

Background and Objectives The purpose of this investigation was to determine the risk of vertical and early contact transmission of human papillomavirus (HPV) in newborn infants based on concordance and sequence match to HPV types in parents. Study Design The genitals of pregnant women and newborns and oral cavity of parents and newborns were analyzed using polymerase chain reaction and DNA sequencing. Data were collected about reproductive health and risk factors for HPV. Results Only one mother/newborn and no father/newborn pair was concordant for an HPV type. All other infected newborns had uninfected or discordant type infected parents. Conclusion The risk of vertical transmission to the oral or genital region of newborns is rare, and transmission between parents and the hospitalized newborn does not appear to occur. Lack of parent/child concordance suggests that newborns detected with HPV in their oral cavity or genitals could have become infected by their mother at untested intervals during pregnancy or in newborns with infection in the oral cavity by other contacts after birth.